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1. Neurofunctional and neuroimaging readouts for designing a preclinical stem-cell therapy trial in experimental stroke

Author: Chloé Dumot, Chrystelle Po, Lucille Capin, Violaine Hubert, Elodie Ong, Matthieu Chourrout, Radu Bolbos, Camille Amaz, Céline Auxenfans, Emmanuelle Canet-Soulas, Claire Rome, Fabien Chauveau, and Marlène Wiart
Subjects: Medicine, Science
Abstract: Abstract With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic
Published: 2022
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2. Clinical Imaging of the Penumbra in Ischemic Stroke: From the Concept to the Era of Mechanical Thrombectomy

Author: Lucie Chalet, Timothé Boutelier, Thomas Christen, Dorian Raguenes, Justine Debatisse, Omer Faruk Eker, Guillaume Becker, Norbert Nighoghossian, Tae-Hee Cho, Emmanuelle Canet-Soulas, and Laura Mechtouff
Subjects: cerebral metabolic rate of oxygen, MRI, PET, ischemic thresholds, penumbra, thrombolysis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: The ischemic penumbra is defined as the severely hypoperfused, functionally impaired, at-risk but not yet infarcted tissue that will be progressively recruited into the infarct core. Early reperfusion aims to save the ischemic penumbra by preventing infarct core expansion and is the mainstay of acute ischemic stroke therapy. Intravenous thrombolysis and mechanical thrombectomy for selected patients with large vessel occlusion has been shown to improve functional outcome. Given the varying speed of infarct core progression among individuals, a therapeutic window tailored to each patient has recently been proposed. Recent studies have demonstrated that reperfusion therapies are beneficial in patients with a persistent ischemic penumbra, beyond conventional time windows. As a result, mapping the penumbra has become crucial in emergency settings for guiding personalized therapy. The penumbra was first characterized as an area with a reduced cerebral blood flow, increased oxygen extraction fraction and preserved cerebral metabolic rate of oxygen using positron emission tomography (PET) with radiolabeled O2. Because this imaging method is not feasible in an acute clinical setting, the magnetic resonance imaging (MRI) mismatch between perfusion-weighted imaging and diffusion-weighted imaging, as well as computed tomography perfusion have been proposed as surrogate markers to identify the penumbra in acute ischemic stroke patients. Transversal studies comparing PET and MRI or using longitudinal assessment of a limited sample of patients have been used to define perfusion thresholds. However, in the era of mechanical thrombectomy, these thresholds are debatable. Using various MRI methods, the original penumbra definition has recently gained a significant interest. The aim of this review is to provide an overview of the evolution of the ischemic penumbra imaging methods, including their respective strengths and limitations, as well as to map the current intellectual structure of the field using bibliometric analysis and explore future directions.
Published: 2022
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3. The Elusive Origin of Atherosclerotic Plaque Calcification

Author: Emmanuelle Canet-Soulas, Laurence Bessueille, Laura Mechtouff, and David Magne
Subjects: atherosclerosis, calcification, chondrocyte, inflammation, cardiovascular morbidity and mortality, Biology (General), QH301-705.5
Abstract: It has been known for decades or even centuries that arteries calcify as they age. Vascular calcification probably affects all adults, since virtually all have atherosclerotic plaques: an accumulation of lipids, inflammatory cells, necrotic debris, and calcium phosphate crystals. A high vascular calcium score is associated with a high cardiovascular mortality risk, and relatively recent data suggest that even microcalcifications that form in early plaques may destabilize plaques and trigger a cardiovascular event. If the cellular and molecular mechanisms of plaque calcification have been relatively well characterized in mice, human plaques appear to calcify through different mechanisms that remain obscure. In this context, we will first review articles reporting the location and features of early calcifications in human plaques and then review the articles that explored the mechanisms though which human and mouse plaques calcify.
Published: 2021
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4. Clinical Imaging of Choroid Plexus in Health and in Brain Disorders: A Mini-Review

Author: Violaine Hubert, Fabien Chauveau, Chloé Dumot, Elodie Ong, Lise-Prune Berner, Emmanuelle Canet-Soulas, Jean-François Ghersi-Egea, and Marlène Wiart
Subjects: choroid plexus, imaging, central nervous system, blood-CSF barrier, inflammation, neurological disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: The choroid plexuses (ChPs) perform indispensable functions for the development, maintenance and functioning of the brain. Although they have gained considerable interest in the last years, their involvement in brain disorders is still largely unknown, notably because their deep location inside the brain hampers non-invasive investigations. Imaging tools have become instrumental to the diagnosis and pathophysiological study of neurological and neuropsychiatric diseases. This review summarizes the knowledge that has been gathered from the clinical imaging of ChPs in health and brain disorders not related to ChP pathologies. Results are discussed in the light of pre-clinical imaging studies. As seen in this review, to date, most clinical imaging studies of ChPs have used disease-free human subjects to demonstrate the value of different imaging biomarkers (ChP size, perfusion/permeability, glucose metabolism, inflammation), sometimes combined with the study of normal aging. Although very few studies have actually tested the value of ChP imaging biomarkers in patients with brain disorders, these pioneer studies identified ChP changes that are promising data for a better understanding and follow-up of diseases such as schizophrenia, epilepsy and Alzheimer’s disease. Imaging of immune cell trafficking at the ChPs has remained limited to pre-clinical studies so far but has the potential to be translated in patients for example using MRI coupled with the injection of iron oxide nanoparticles. Future investigations should aim at confirming and extending these findings and at developing translational molecular imaging tools for bridging the gap between basic molecular and cellular neuroscience and clinical research.
Published: 2019
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5. Spatio-Temporal Characterization of Brain Inflammation in a Non-human Primate Stroke Model Mimicking Endovascular Thrombectomy

Author: Guillaume Becker, Justine Debatisse, Margaux Rivière, Claire Crola Da Silva, Maude Beaudoin-Gobert, Omer Eker, Océane Wateau, Tae Hee Cho, Marlène Wiart, Léon Tremblay, Nicolas Costes, Inès Mérida, Jérôme Redouté, Christelle Léon, Jean-Baptiste Langlois, Didier Le Bars, Sophie Lancelot, Norbert Nighoghossian, Laura Mechtouff, and Emmanuelle Canet-Soulas
Subjects: Pharmacology, Pharmacology (medical), Neurology (clinical)
Abstract: Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [11C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [11C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [11C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [15O2]H2OPET imaging. [11C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation.
Published: 2023
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6. PREMISE: A database of 20Macaca FascicularisPET/MRI brain imaging available for research

Author: Lucie Chalet, Justine Debatisse, Oceane Wateau, Timothe Boutelier, Marlène Wiart, Nicolas Costes, Ines Merida, Jérôme Redouté, Jean-Baptiste Langlois, Sophie Lancelot, Christelle Léon, Tae-Hee Cho, Laura Mechtouff, Omer Faruk Eker, Norbert Nighoghossian, Emmanuelle Canet-Soulas, and Guillaume Becker
Abstract: Non-human primate (NHP) studies are unique in translational research, especially in neurosciences and neuroimaging approaches are a preferred method for scaling cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community while limiting the number of animals used in research. We present here a simultaneous PET/MR dataset of 20 Macaca Fascicularis structured according to the Brain Imaging Data Structure (BIDS) standards. This database contains multiple MRI sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assessed all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity. The database is stored and available through the PRIME-DE consortium repository.
Published: 2023
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7. Microglial phagocytosis dysfunction in stroke is driven by energy depletion and induction of autophagy

Author: Sol Beccari, Virginia Sierra-Torre, Jorge Valero, Marta Pereira-Iglesias, Mikel García-Zaballa, Federico N. Soria, Laura De Las Heras-Garcia, Alejandro Carretero-Guillen, Estibaliz Capetillo-Zarate, Maria Domercq, Paloma R. Huguet, David Ramonet, Ahmed Osman, Wei Han, Cecilia Dominguez, Travis E. Faust, Omar Touzani, Olatz Pampliega, Patricia Boya, Dorothy Schafer, Guillermo Mariño, Emmanuelle Canet-Soulas, Klas Blomgren, Ainhoa Plaza-Zabala, Amanda Sierra, Ministerio de Ciencia e Innovación (España), Ministerio de Industria y Competitividad (España), Fundación Tatiana Pérez de Guzmán el Bueno, Basque Government Department of Education, Beccari, Sol, Sierra-Torre, Virginia, Valero, Jorge, Soria, Federico N., De Las Heras-Garcia, Laura, Carretero-Guillén, Alejandro, Capetillo-Zarate, Estibaliz, Domercq, María, Ramonet, David, Osman, Ahmed M., Faust, Travis E., Touzani, Omar, Pampliega, Olatz, Boya, Patricia, Schafer, Dorothy, Mariño, Guillermo, Canet-Soulas, Emmanuelle, Blomgren, Klas, Plaza-Zabala, Ainhoa, and Sierra, Amanda
Subjects: Stroke, Phagocytosis, Ischemia, Autophagy, Cell Biology, Microglia, Rapamycin, tMCAo, Lysosomes, Molecular Biology
Abstract: 31 p.-12 fig.-1 tab. We dedicate this paper to Takashi Umekawa, who generated the HI model at the Karolinska Institute, and unfortunately passed away in 2018., Microglial phagocytosis of apoptotic debris prevents buildup damage of neighbor neurons and inflammatory responses. Whereas microglia are very competent phagocytes under physiological conditions, we report their dysfunction in mouse and preclinical monkey models of stroke (macaques and marmosets) by transient occlusion of the medial cerebral artery (tMCAo). By analyzing recently published bulk and single cell RNA sequencing databases, we show that the phagocytosis dysfunction was not explained by transcriptional changes. In contrast, we demonstrate that the impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrient deprivation (OND), which led to reduced process motility, lysosomal exhaustion, and the induction of a protective macroautophagy/autophagy response in microglia. Basal autophagy, in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using pharmacological and transgenic approaches. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro, where it even had a detrimental effect on microglia, suggesting that modulating microglial autophagy to optimal levels may be a hard to achieve goal. Nonetheless, our results show that pharmacological interventions, acting directly on microglia or indirectly on the brain environment, have the potential to recover phagocytosis efficiency in the diseased brain. We propose that phagocytosis is a therapeutic target yet to be explored in stroke and other brain disorders and provide evidence that it can be modulated in vivo using rapamycin. Abbreviations: AIF1/IBA1: allograft inflammatory factor 1; AMBRA1: autophagy/beclin 1 regulator 1; ATG4B: autophagy related 4B, cysteine peptidase; ATP: adenosine triphosphate; BECN1: beclin 1, autophagy related; CASP3: caspase 3; CBF: cerebral blood flow; CCA: common carotid artery; CCR2: chemokine (C-C motif) receptor 2; CIR: cranial irradiation; Csf1r/v-fms: colony stimulating factor 1 receptor; CX3CR1: chemokine (C-X3-C motif) receptor 1; DAPI: 4’,6-diamidino-2-phenylindole; DG: dentate gyrus; GO: Gene Ontology; HBSS: Hanks’ balanced salt solution; HI: hypoxia-ischemia; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MCA: medial cerebral artery; MTOR: mechanistic target of rapamycin kinase; OND: oxygen and nutrient deprivation; Ph/A coupling: phagocytosis-apoptosis coupling; Ph capacity: phagocytic capacity; Ph index: phagocytic index; SQSTM1: sequestosome 1; RNA-Seq: RNA sequencing; TEM: transmission electron microscopy; tMCAo: transient medial cerebral artery occlusion; ULK1: unc-51 like kinase 1. © 2023 The Author(s)., This work was supported by grants from the Spanish Ministry of Science and Innovation Competitiveness MCIN/AEI/10.13039/501100011033 (https://www.ciencia.gob.es/) and ERDF “A way to make Europe” (RTI2018-099267-B-I00 and RYC-2013-12817 to AS; RTI2018–097948-A-100 and RYC-2016–20480 to OP), a Tatiana Foundation Award (P-048-FTPGB 2018) to AS a Basque Government Department of Education project (PIBA 2020_1_0030; http://www.euskadi.eus/basque-government/department-education/) to AS, a Basque Government Department of Economic development, Sustainability and environment (ELKARTEK KK-2020/00034; https://www.spri.eus/en/) to ECZ, and . SB is recipient of predoctoral fellowship from the Spanish Ministry of Economy and Competitiveness, and VST is recipient of predoctoral fellowship from the Basque Government.
Published: 2023
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8. Contributors

Author: Maha R.A. Abdollah, Mir Hilal Ahmad, Berta Alcover-Sanchez, Alfonso Alfaro Rodríguez, Marwa A. Ali, Karim A. Alkadhi, Georg Auburger, Meheli Banerjee, Christoph G. Baums, Daria V. Belan, Tom Bleeser, Larisa Bobrovskaya, Hayrunnisa Bolay, Joline E. Brandenburg, Josiane Budni, Jennifer Burnsed, Antonio Cadiz, Katherine Carlin, Raul Chavez-Valdez, Win Ning Chen, Jacques-Olivier Coq, Stephen J. Crocker, Beatriz Cubelos, I.S. Darshini, Nicole de Buhr, Justine Debatisse, Isaac Deng, Jan Deprest, Sarah Devroe, Maria Laura Cecconi dos Santos, Olga Doszyn, Tomasz Dulski, Omer Faruk Eker, Irina V. Ekimova, Barbara Falquetto, Ana Fernández, Matthew J. Fogarty, Abdelrahman Y. Fouda, Luis Gandía, Antonio G. García, Angélica González Maciel, Denis Grandgirard, Bernadette E. Grayson, David A. Greenberg, Natalia Gulyaeva, Sangeetha Gupta, Bora Gürer, Omar Guzmán-Quevedo, Daniel Gyamfi, Sarah Hamimi, Junqiu He, Sung-Ha Hong, Hiroyuki Ida, Salinee Jantrapirom, Lauren L. Jantzie, Mykola Kadzhaya, Jyotshna Kanungo, Ginpreet Kaur, Gabriela Serafim Keller, Sally Kelliny, Olga N. Kokiko-Cochran, Ilia Komoltsev, P. Pramod Kumar, Diego Cabral Lacerda, Geoffrey A. Lambert, Ksenia V. Lapshina, Tally M. Largent-Milnes, Ngoc Dung Le, Stephen L. Leib, Aidan A. Levine, Lulin Li, Erika Liktor-Busa, Fang Liu, Sufang Liu, Jian Luo, Raul Manhães-de-Castro, Devin W. McBride, Eduarda Behenck Medeiros, Marita Meurer, Brandon A. Miller, Amal Chandra Mondal, Thiago S. Moreira, S. Priya Narayanan, Andy Nguyen, Andrii Panteleichuk, Nuria Paricio, Yuri F. Pastukhov, Vinood B. Patel, Eugene Pedachenko, Misha Perouansky, Taras Petriv, Luca Lo Piccolo, K.V. Harish Prashanth, Victor R. Preedy, Cristina Puig, Rajkumar Rajendram, Ramalakshmi Ramasamy, Santhamani Ramasamy, Manuel Alejandro Ramirez-Lee, Trenton J. Ray, Lisienny Campoli Tono Rempel, Miriam Renz, Steffen Rex, Rafael Reynoso Robles, Susanna Ricci, Sandra Rieger, Shenandoah Robinson, Rosa María Romero Velázquez, Robert Rümmler, Francisco José Sanz, Serhii Savosko, Nada K. Sedky, Nesli-Ece Sen, Mohd. Farooq Shaikh, Shengshuai Shan, Uma Sharma, Anna Shmeleva, Gary C. Sieck, Pascal Siegert, Allie M. Smith, Phillip P. Smith, Cristina Solana-Manrique, Emmanuelle Canet Soulas, Rhea Subba, Selvakumar Subbian, Ana C. Takakura, John C. Talpos, Kin Yip Tam, Feng Tao, Zoe Tapp, Baban S Thawkar, Mai F. Tolba, Ana Elisa Toscano, Masahiro Tsuji, Ignacio Valenzuela, Marc Van de Velde, Lennart Van der Veeken, Libor Velíšek, Jana Velíšková, Diego Bulcão Visco, Sydney M. Vita, Maren von Köckritz-Blickwede, Doga Vuralli, Jennifer L. Walters, David A. Wassarman, Océane Wateau, Masamitsu Yamaguchi, Hideki Yoshida, Xin-Fu Zhou, and Justyna Zmorzynska
Published: 2023
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9. Use of metal-based contrast agents for in vivo MR and CT imaging of phagocytic cells in neurological pathologies

Author: Marlène Wiart, Clément Tavakoli, Violaine Hubert, Inès Hristovska, Chloé Dumot, Stéphane Parola, Frédéric Lerouge, Fabien Chauveau, Emmanuelle Canet-Soulas, Olivier Pascual, David P. Cormode, Emmanuel Brun, Hélène Elleaume, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut NeuroMyoGène (INMG), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Synaptopathies et Autoanticorps [Lyon] (SynatAc), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Hospices Civils de Lyon, Departement de Neurologie (HCL), Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, ANR-18-CE19-0003,BREAKTHRU,Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires(2018), ANR-15-CE18-0026,NanoBrain,Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale(2015), European Project: 668142,H2020,H2020-PHC-2015-two-stage,SPCCT(2016), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Wiart, Marlene, APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires - - BREAKTHRU2018 - ANR-18-CE19-0003 - AAPG2018 - VALID, Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale - - NanoBrain2015 - ANR-15-CE18-0026 - AAPG2015 - VALID, and In Vivo Spectral Photon Counting CT Molecular Imaging in Cardio- and Neuro-Vascular Diseases - SPCCT - - H20202016-01-01 - 2019-12-31 - 668142 - VALID
Subjects: Phagocytes, Phagocytic cells, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, General Neuroscience, Metal-based nanoparticles, Contrast Media, Gadolinium, Contrast agents, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Magnetic resonance imaging, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nervous System Diseases, Tomography, X-Ray Computed, Computed tomography, Neurological diseases
Abstract: International audience; The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT). In this review article, we summarize the different labelling strategies, contrast agents, and in vivo imaging modalities that can be used to monitor cells with phagocytic activity in the central nervous system using MRI and CT, with a focus on clinical applications. Metal-based nanoparticle contrast agents such as gadolinium, gold and iron are ideal candidates for these applications as they have favourable magnetic and/or radiopaque properties and can be fine-tuned for optimal uptake by phagocytic cells. However, they also come with downsides due to their potential toxicity, especially in the brain where they might accumulate. We therefore conclude our review by discussing the pitfalls, safety and potential for clinical translation of these metal-based neuroimaging techniques. Early results in patients with neuropathologies such as multiple sclerosis, stroke, trauma, cerebral aneurysm and glioblastoma are promising. If the challenges represented by safety issues are overcome, phagocytic cells imaging will be a very valuable tool for studying and understanding the inflammatory response and evaluating treatments that aim at mitigating this response in patients with neurological diseases.
Published: 2023
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10. Non-human primates models of stroke: Imaging studies in cerebral ischemia in Macaca fascicularis

Author: Emmanuelle Canet Soulas, Justine Debatisse, Océane Wateau, and Omer Faruk Eker
Published: 2023
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11. A novel fluorescence imaging of myoglobin redox STATE reveals early reperfusion-injury in myocardium

Author: Sally Badawi, Clémence Leboullenger, Matthieu Chourout, Yves Gouriou, Alexandre Paccalet, Chris Berd, Bruno Pillot, Lionel Augeul, Radu Bolbos, Antonino Bongiovani, Michel Ovize, Nathan Mewton, Thomas Bochaton, Meryem Tardivel, Emmanuelle Canet-Soulas, Claire Corla da Silva, and Gabriel Bidaux
Subjects: Cardiology and Cardiovascular Medicine, Molecular Biology
Published: 2022
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12. Exercise Does Not Protect Against Peripheral and Central Effects of a High Cholesterol Diet Given Ad Libitum in Old ApoE-/- Mice

Author: Vanessa Di Cataldo, Alain Geloën, Jean-Baptiste Langlois, Fabien Chauveau, Benoît Thézé, Violaine Hubert, Marlène Wiart, Erica N Chirico, Jennifer Rieusset, Hubert Vidal, Vincent Pialoux, and Emmanuelle Canet-Soulas
Subjects: Atherosclerosis, Oxidative Stress, physical activity, overfeeding, Neuroinflammation imaging, Physiology, QP1-981
Abstract: Aim:Advanced atherosclerosis increases inflammation and stroke risk in the cerebral vasculature. Exercise is known to improve cardio-metabolic profiles when associated with a caloric restriction, but it remains debated whether it is still beneficial without the dietary control. The aim of this study was to determine both the peripheral and central effects of exercise training combined with a cholesterol-rich diet given ad libitum in old ApoE-/- mice.Methods:45-weeks old obese ApoE-/-mice fed with a high cholesterol diet ad libitum were divided into Exercise-trained (EX; running wheel free access) and Sedentary (SED) groups. Insulin tolerance and brain imaging were performed before and after the twelve-weeks training. Tissue insulin resistance, oxidative stress and inflammation markers in plasma, aorta and brain were then assessed.Results:In EX ApoE-/- mice, no beneficial effect of exercise was observed on weight, abdominal fat, metabolic parameters, oxidative stress, or inflammation compared to SED. Despite the regular exercise training in ApoE-/- EX mice (mean of 12.5 km/week during twelve weeks), brain inflammation imaging score was significantly associated with increased blood brain barrier (BBB) leakage evaluated by imaging follow-up (r²=0.87; p=0.049) with a faster evolution compared to SED ApoE-/-mice. Conclusion:We conclude that in a context of high cardio-metabolic risk, exercise does not provide any protective effect in old ApoE-/- animals under high cholesterol diet given ad libitum. Peripheral (insulin sensitivity and oxidative/inflammatory status) but also central features (BBB preservation and protection against inflammation) did not show any benefits of exercise. Indeed, there was a fast induction of irreversible brain damage that was more pronounced in exercise-trained ApoE-/- mice.
Published: 2016
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13. A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Author: F. Taborik, Karine Portier, Norbert Nighoghossian, Adrien Oudotte, Michaël Verset, Thomas Troalen, Omer Eker, Denis Vivien, Inés Mérida, Christelle Leon, Christian Tourvieille, Didier Le Bars, Emmanuelle Canet-Soulas, Michel Ovize, Hugues Contamin, Nicolas Costes, Nikolaos Makris, Véronique Agin, Joachim Confais, Tae-Hee Cho, Mohamed Aggour, Sophie Lancelot, Justine Debatisse, Jean-Baptiste Langlois, Océane Wateau, Marjorie Villien, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Cynbiose, CYNBIOSE, Institut Claude Bourgelat (ICLB), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Siemens Healthcare [France], Siemens AG [Munich], Institute of Electronic Structure and Laser (FORTH-IESL), Foundation for Research and Technology - Hellas (FORTH), Radiopharmaceutical and Neurochemical Biomarkers Team (BioRaN), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology, Hospices Civils de Lyon (HCL), Laboratoire de Chimie de la Matière Condensée de Paris (site ENSCP) (LCMCP (site ENSCP)), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), French Ministry of Higher Education and Research (ANRT), ANR-15-CE17-0020,CYCLOPS,CYCLOsporine A : effet neuroprotecteur dans un modèle Primate de Stroke en imagerie(2015), ANR-16-RHUS-0009,MARVELOUS,MARVELOUS(2016), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], Executive Function, 0302 clinical medicine, Occlusion, Stroke, Thrombectomy, 0303 health sciences, Behavior, Animal, Endovascular Procedures, Infarction, Middle Cerebral Artery, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Neurology, Blood-Brain Barrier, Motor Skills, Reperfusion Injury, Middle cerebral artery, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Ischemia, Context (language use), ischemia–reperfusion, Asymptomatic, Lesion, 03 medical and health sciences, medicine.artery, Internal medicine, medicine, Animals, cardiovascular diseases, Thrombus, Ischemic Stroke, 030304 developmental biology, business.industry, Original Articles, medicine.disease, Disease Models, Animal, Macaca fascicularis, Endovascular non-human primate stroke model, PET-MRI imaging, Positron-Emission Tomography, neurofunctional tests, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: International audience; Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.
Published: 2020
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14. Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis

Author: Laurence Bessueille, Lynn Kawtharany, Thibaut Quillard, Claudia Goettsch, Anne Briolay, Nirina Taraconat, Stéphane Balayssac, Véronique Gilard, Saida Mebarek, Olivier Peyruchaud, François Duboeuf, Caroline Bouillot, Anthony Pinkerton, Laura Mechtouff, René Buchet, Eva Hamade, Kazem Zibara, Caroline Fonta, Emmanuelle Canet-soulas, Jose luis Millan, David Magne, Fonta, Caroline, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Sanford Burnham Prebys Medical Discovery Institute, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lebanese University [Beirut] (LU), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), BIBAC - Chimie analytique et interactions biomolécules - matière molle biomimétique (BIBAC), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: calcification, inflammation, Physiology (medical), Biochemistry (medical), Public Health, Environmental and Occupational Health, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Medicine, TNAP, liver, metabolic syndrome
Abstract: International audience; Calcium accumulation in atherosclerotic plaques predicts cardiovascular mortality, but the mechanisms responsible for plaque calcification and how calcification impacts plaque stability remain debated. Tissue-nonspecific alkaline phosphatase (TNAP) recently emerged as a promising therapeutic target to block cardiovascular calcification. In this study, we sought to investigate the effect of the recently developed TNAP inhibitor SBI-425 on atherosclerosis plaque calcification and progression. TNAP levels were investigated in ApoE-deficient mice fed a high-fat diet from 10 weeks of age and in plaques from the human ECLAGEN biocollection (101 calcified and 14 non-calcified carotid plaques). TNAP was inhibited in mice using SBI-425 administered from 10 to 25 weeks of age, and in human vascular smooth muscle cells (VSMCs) with MLS-0038949. Plaque calcification was imaged in vivo with 18F-NaF-PET/CT, ex vivo with osteosense, and in vitro with alizarin red. Bone architecture was determined with µCT. TNAP activation preceded and predicted calcification in human and mouse plaques, and TNAP inhibition prevented calcification in human VSMCs and in ApoE-deficient mice. More unexpectedly, TNAP inhibition reduced the blood levels of cholesterol and triglycerides, and protected mice from atherosclerosis, without impacting the skeletal architecture. Metabolomics analysis of liver extracts identified phosphocholine as a substrate of liver TNAP, who's decreased dephosphorylation upon TNAP inhibition likely reduced the release of cholesterol and triglycerides into the blood. Systemic inhibition of TNAP protects from atherosclerosis, by ameliorating dyslipidemia, and preventing plaque calcification.
Published: 2022
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15. Neurofunctional and neuroimaging readouts for designing a preclinical stem-cell therapy trial in experimental stroke

Author: Camille Amaz, Marlène Wiart, Chrystelle Po, Claire Rome, Matthieu Chourrout, Chloé Dumot, Céline Auxenfans, Radu Bolbos, Elodie Ong, Emmanuelle Canet-Soulas, Fabien Chauveau, Violaine Hubert, Lucille Capin, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-18-CE19-0003,BREAKTHRU,Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires(2018), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Wiart, Marlene, and APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires - - BREAKTHRU2018 - ANR-18-CE19-0003 - AAPG2018 - VALID
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Multidisciplinary, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Stem-cell therapy, medicine.disease, Rats, 3. Good health, Stroke, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neuroimaging, nervous system, medicine, Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, Ischemic Stroke
Abstract: With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic < striatal < corticostriatal. Intracerebral administration did not impact these readouts. After sample size calculation (18-147 rats per group according to the endpoint considered), we conclude that a therapeutic trial based on both readouts would be feasible only in the framework of a multicenter trial.
Published: 2021
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16. Microglial phagocytosis dysfunction during stroke is prevented by rapamycin

Author: Jorge Valero, Ahmed M. Osman, Alejandro Carretero-Guillén, Guillermo Mariño, Amanda Sierra, Wei Han, Mikel Garcia-Zaballa, David Ramonet, Dorothy P. Schafer, Omar Touzani, Travis E Faust, Patricia Boya, Estibaliz Capetillo-Zarate, Virginia Sierra-Torre, Emmanuelle Canet-Soulas, Ainhoa Plaza-Zabala, Paloma Huguet, María Domercq, Sol Beccari, Klas Blomgren, and Cecilia A. Dominguez
Subjects: medicine.anatomical_structure, Microglia, Apoptosis, business.industry, In vivo, Phagocytosis, Autophagy, Cell, medicine, Motility, business, Intracellular, Cell biology
Abstract: Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechanisms that enable them to recognize and degrade several types of cargo, including neurons undergoing apoptotic cell death. While microglia are very competent phagocytes of apoptotic cells under physiological conditions, here we report their dysfunction in mouse and monkey (Macaca fascicularis and Callithrix jacchus) models of stroke by transient occlusion of the medial cerebral artery (tMCAo). The impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrients deprivation (OND), which led to reduced process motility, lysosomal depletion, and the induction of a protective autophagy response in microglia. Basal autophagy, which is in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using knock-out models of autophagy genes and the autophagy inhibitor MRT68921. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro. These results suggest a more complex role of microglia in stroke than previously acknowledged, classically related to the inflammatory response. In contrast, here we demonstrate the impairment of apoptotic cell phagocytosis, a microglial function critical for brain recovery. We propose that phagocytosis is a therapeutic target yet to be explored and provide evidence that it can be modulated in vivo using rapamycin, setting the stage for future therapies for stroke patients.
Published: 2021
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17. Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis.

Author: Antoine Millon, Monica Sigovan, Loic Boussel, Jean-Louis Mathevet, Vanessa Louzier, Christian Paquet, Alain Geloen, Nicolas Provost, Zouher Majd, David Patsouris, Andre Serusclat, and Emmanuelle Canet-Soulas
Subjects: Medicine, Science
Abstract: Atherosclerotic plaque development in the arterial wall is the result of complex interaction between the wall's endothelial layer and blood hemodynamics. However, the interaction between hemodynamic parameters and inflammation in plaque evolution is not yet fully understood. The aim of the present study was to investigate the relation between wall shear stress (WSS) and vessel wall inflammation during atherosclerotic plaque development in a minipig model of carotid stenosis.A surgical procedure was performed to create left common carotid artery stenosis by placement of a perivascular cuff in minipigs under atherogenic diet. Animals were followed up on 3T MRI, 1 week after surgery and 3, 6, and 8 months after initiation of the diet. Computational fluid dynamics simulation estimated WSS distribution for the first imaging point. Vascular geometries were co-registered for direct comparison of plaque development and features (Gadolinium- and USPIO-Contrast Enhanced MRI, for permeability and inflammation respectively) with the initial WSS. Histological analysis was performed and sections were matched to MR images, based on spatial landmarks.Vessel wall thickening, permeability and inflammation were observed distally from the stenosis. They were eccentric and facing regions of normal wall thickness. Histological analysis confirmed eccentric plaque formation with lipid infiltration, intimal thickening and medial degradation. High phagocytic activity in the stenosis region was co-localized with high WSS, corresponding to intense medial degradation observed on histology samples.Lower WSS promotes atherosclerotic plaque development distal to an induced stenosis. Vascular and perivascular inflammation locations were predominant in the high WSS stenosis segment, where medial thinning was the major consequence.
Published: 2015
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18. Metabolic outcome of female mice exposed to a mixture of low-dose pollutants in a diet-induced obesity model.

Author: Danielle Naville, Emmanuel Labaronne, Nathalie Vega, Claudie Pinteur, Emmanuelle Canet-Soulas, Hubert Vidal, and Brigitte Le Magueresse-Battistoni
Subjects: Medicine, Science
Abstract: Pollutants are suspected to contribute to the etiology of obesity and related metabolic disorders. Apart from occupational exposure which concerns a subset of chemicals, humans are mostly exposed to a large variety of chemicals, all life-long and at low doses. Food ingestion is a major route of exposure and it is suggested that pollutants have a worsened impact when combined with a high-fat diet. In the experimental studies described herein, we aimed to add further evidence on the metabolic impact of food pollutants using a recently set up model in which mice are life-long fed a high-fat/high-sucrose diet (HFSD) with/without common food pollutants shown to exhibit metabolic disrupting activities. Specifically, this mixture comprised bisphenol A, dioxin, polychlorobiphenyl PCB153, and phthalate and was added in HFSD at doses resulting in mice exposure at the Tolerable Daily Intake dose range for each pollutant. We herein focused on the 7-week-old females which exhibited early signs of obesity upon HFSD feeding. We observed no signs of toxicity and no additional weight gain following exposure to the mixture but alleviated HFSD-induced glucose intolerance in the absence of alteration of gluconeogenesis and steatosis. It suggested that the observed metabolic improvement was more likely due to effects on muscle and/or adipose tissues rather than on the liver. Consistently, female mice exhibited enhanced lean/fat mass ratio and skeletal muscle insulin sensitivity. Moreover, expression levels of inflammatory markers were reduced in adipose tissue at 7 but enhanced at 12 weeks of age in agreement with the inverse alterations of glucose tolerance observed at these ages upon pollutant exposure in the HFSD-fed females. Collectively, these data suggest apparent biphasic effects of pollutants upon HFSD feeding along with obesity development. These effects were not observed in males and may depend on interactions between diet and pollutants.
Published: 2015
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19. Advanced atherosclerotic plaques in animal models versus human lesions: Key elements to translation

Author: Emmanuelle Canet Soulas and Saami K. Yazdani
Subjects: business.industry, Medicine, Translation (biology), business, Neuroscience
Abstract: Animal models have been extensively used to understand atherogenesis and the complex biological mechanisms of atherosclerosis. Yet, their advanced plaque morphologies may have distinct features from human coronary lesions and strikingly, they often do not lead to acute cardiac events, at least in mice models. These particularities will be presented in the major models of advanced plaques together with their respective specific localizations. Next, in light of recent major translational advances regarding the role of inflammation in plaque vulnerability, the main findings from animal models to human applications will be given, opening new diagnoses and therapeutic targets. Finally, biomechanics has mainly been evaluated in human plaques, but differences and similarities between animal models and human lesions shed new light on prediction markers of acute events.
Published: 2021
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20. Contributors

Author: Ali C. Akyildiz, Antonios P. Antoniadis, Lambros S. Athanasiou, Hilary E. Barrett, Kristen Billiar, Emmanuelle Canet Soulas, Luis Cardoso, Claire Cawthon, Yiannis S. Chatzizisis, Claudio Chiastra, Myriam Cilla, Guy Cloutier, Ricardo Coppel, Catherine Demos, François Dérimay, Gabriele Dubini, Elazer R. Edelman, Richard L. Ehman, Gérard Finet, Pak-Wing Fok, T. Christian Gasser, Don P. Giddens, Frank J.H. Gijsen, Erin Goerlich, Armida Gómez, Guillaume Goudot, Xiaoya Guo, Allison G. Hays, Ulf Hedin, Gerhard A. Holzapfel, Haibo Jia, Hanjoong Jo, Roger D. Kamm, Ghassan S. Kassab, Arunark Kolipaka, Elisa E. Konofagou, Manuel Lagache, Álvaro T. Latorre, Simon Le Floc'h, Stephanie Lehoux, Genshan Ma, Akiko Maehara, Mauro Malvè, Jean-Louis Martiel, Miguel A. Martínez, Takeo Matsumoto, Mitsuaki Matsumura, Francesco Migliavacca, Gary S. Mintz, Navid Mohammad Mirzaei, David Molony, Farhad Rikhtegar Nezami, Jacques Ohayon, John N. Oshinski, Estefanía Peña, Mathieu Pernot, Roderic I. Pettigrew, William L. Pomeroy, Gilles Rioufol, Joy Roy, Habib Samady, Sarah E. Shelton, Matthias Stuber, Antoine Tacheau, Ian Tamargo, Dalin Tang, Lucas H. Timmins, Emily A. Turner, Liang Wang, Sheldon Weinbaum, Robert G. Weiss, Richard D. White, Chun Yang, Saami K. Yazdani, Jie Zheng, and Jian Zhu
Published: 2021
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21. Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid

Author: Laura, Mechtouff, Monica, Sigovan, Philippe, Douek, Nicolas, Costes, Didier, Le Bars, Adeline, Mansuy, Julie, Haesebaert, Alexandre, Bani-Sadr, Jérémie, Tordo, Patrick, Feugier, Antoine, Millon, Stéphane, Luong, Salim, Si-Mohamed, Diane, Collet-Benzaquen, Emmanuelle, Canet-Soulas, Thomas, Bochaton, Claire, Crola Da Silva, Alexandre, Paccalet, David, Magne, Yves, Berthezene, and Norbert, Nighoghossian
Subjects: Positron-Emission Tomography, Calcinosis, Humans, Sodium Fluoride, Carotid Stenosis, Magnetic Resonance Imaging, Plaque, Atherosclerotic
Abstract: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) usingWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent
Published: 2020

22. Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity

Author: Mathilde Mura, Vincent Pialoux, Erica N. Chirico, Emmanuelle Canet-Soulas, Antoine Millon, and Pauline Mury
Subjects: Risk, 0301 basic medicine, Adhesion (medicine), Physical Therapy, Sports Therapy and Rehabilitation, Inflammation, Disease, 030204 cardiovascular system & hematology, medicine.disease_cause, Neovascularization, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Orthopedics and Sports Medicine, Endothelial dysfunction, Exercise, business.industry, Fibrous cap, medicine.disease, Vulnerable plaque, Plaque, Atherosclerotic, 3. Good health, Oxidative Stress, 030104 developmental biology, medicine.anatomical_structure, Immunology, Disease Progression, medicine.symptom, business, Oxidative stress
Abstract: Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.
Published: 2018
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23. Tissue-nonspecific alkaline phosphatase inhibition reduces atherosclerotic plaque development

Author: Saida Mebarek, F. Duboeuf, Emmanuelle Canet-Soulas, Thibaut Quillard, K. Zibara, José Luis Millán, Laurence Bessueille, L. Kawtharany, Anne Briolay, Claudia Goettsch, O. Peyruchaud, D. Magne, A. Pinkerton, and C. Bouillot
Subjects: Chemistry, Cardiology and Cardiovascular Medicine, Tissue-nonspecific Alkaline Phosphatase, Molecular biology
Published: 2021
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24. La RMN Concepts, méthodes et applications

Author: Daniel Canet, Jean-Claude Boubel, Emmanuelle Canet Soulas, Institut Jean Barriol (IJB), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Canet, Daniel
Subjects: [CHIM] Chemical Sciences, [CHIM]Chemical Sciences, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

25. TNAP as a therapeutic target for cardiovascular calcification - a discussion of its pleiotropic functions in the body

Author: Claudia, Goettsch, Agnieszka, Strzelecka-Kiliszek, Laurence, Bessueille, Thibaut, Quillard, Laura, Mechtouff, Slawomir, Pikula, Emmanuelle, Canet-Soulas, Jose Luis, Millan, Caroline, Fonta, David, Magne, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université Bretagne Loire (UBL), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sanford Burnham Prebys Medical Discovery Institute, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CarMeN, laboratoire, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Inflammation, Therapeutic target, [SDV]Life Sciences [q-bio], Reviews, Cardiovascular Agents, Arteries, Alkaline Phosphatase, equipment and supplies, Substrate Specificity, [SDV] Life Sciences [q-bio], Tissue non-specific alkaline phosphatase, Animals, Humans, AcademicSubjects/MED00200, Enzyme Inhibitors, Phosphorylation, Erratum, Cardiovascular calcification, Vascular Calcification, Signal Transduction, Inhibition
Abstract: Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP’s functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo., Graphical Abstract
Published: 2020
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26. Physiopathologie cardiovasculaire intégrative : apports et enjeux de l’imagerie moléculaire

Author: Emmanuelle Canet-Soulas
Subjects: Gynecology, medicine.medical_specialty, General Veterinary, business.industry, Accidents vasculaires ischémiques, syndrome coronarien, AVC, athérosclérose, inflammation, imagerie moléculaire, translationnel, medicine, cardiovascular diseases, business, translational, Acute ischemic events, coronary syndrome, stroke, atherosclerosis, molecular imaging
Abstract: Acute cardio and neurovascular ischemic events, namely acute coronary syndrome (ACS) and acute ischemic stroke (AIS), are major public health concerns. Restoring blood flow with mechanical endovascular treatment is systematic for ACS and is revolutionizing stroke management. Reestablishing blood supply is the first line of treatment but secondary ischemia-reperfusion damages are frequent and have a major impact on patient prognosis. Yet, there is no available therapy and the pathophysiological mechanisms and their spatio-temporal evolution are still incompletely understood. Among them, inflammation is a key player but with uncertain outcome at the individual level as it can be either beneficial or deleterious. In this context, what are the future translational approaches for diagnosis and therapy ? Today, who are the actors of this research and how can we train the future specialists ?, La prise en charge des accidents vasculaires ischémiques cardiaques (syndromes coronariens aigus ou SCA) et cérébraux (AVC) est un enjeu de santé publique majeur. Pour restaurer le flux sanguin, le traitement mécanique endovasculaire est systématique pour le SCA, et révolutionne actuellement le traitement de l’AVC. Le rétablissement de l’apport sanguin est la première ligne d’action thérapeutique, mais des dégâts secondaires à l’épisode d’ischémie-reperfusion interviennent, qui mettent en jeu le pronostic des patients. Aucun traitement efficace n’existe et leurs mécanismes physiopathologiques comme leur évolution spatio-temporelle sont encore mal circonscrits. Parmi ceux-ci, la réaction inflammatoire est un acteur clé, mais nul à ce jour ne peut en prédire l’issue tant son rôle peut se révéler à l’échelle individuelle bénéfique ou délétère. Dans ce contexte, quelles en seront les approches translationnelles diagnostiques et thérapeutiques ? Aujourd’hui, quels sont les acteurs de ces avancées médicales et comment former ceux de demain ?, Canet-Soulas Emmanuelle. Physiopathologie cardiovasculaire intégrative : apports et enjeux de l’imagerie moléculaire. In: Bulletin de l'Académie Vétérinaire de France tome 173, 2020. pp. 185-191.
Published: 2020

27. Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

Author: Alexandre Paccalet, Laura Mechtouff, Emmanuelle Canet-Soulas, Nicolas Costes, Stephane Luong, Antoine Millon, Yves Berthezène, Patrick Feugier, Thomas Bochaton, Salim Si-Mohamed, Claire Crola Da Silva, Alexandre Bani-Sadr, Didier Le Bars, Norbert Nighoghossian, Monica Sigovan, Diane Collet-Benzaquen, David Magne, Adeline Mansuy, Julie Haesebaert, Philippe Douek, Jérémie Tordo, and Hospices Civils de Lyon, Departement de Neurologie (HCL)
Subjects: medicine.diagnostic_test, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Magnetic resonance imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, medicine.disease, Asymptomatic, Culprit, 030218 nuclear medicine & medical imaging, body regions, 03 medical and health sciences, Stenosis, 0302 clinical medicine, Carotid artery plaque, medicine, Mineral metabolism, Radiology, Nuclear Medicine and imaging, Tomography, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Nuclear medicine, Stroke, ComputingMilieux_MISCELLANEOUS
Abstract: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. We included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. 18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.
Published: 2020
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28. Critical appraisal of STAT3 pattern in adult cardiomyocytes

Author: Emmanuelle Canet-Soulas, Bruno Pillot, Noelle Gallo Bona, Mazen Kurdi, George W. Booz, Sally Badawi, Lionel Augeul, Michel Ovize, Melanie Paillard, Gabriel Bidaux, Zeina Harhous, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Lebanese University [Beirut] (LU), University of Mississippi Medical Center (UMMC), This work was supported by the IHU OPeRa (ANR-10-IBHU-004) within the program 'Investissements d'Avenir' operated by the French National Research Agency (ANR). Zeina Harhous was supported by the 'Association de Specialisation et d'orientation Scientifique'. Sally Badawi was supported by the Council for Scientific Research and Lebanese University fellowship (CNRS-L) program and the Eiffel scholarship program of excellence of Campus France. We acknowledge the financial support from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Sciences and Health) within the framework of the cancer plan for Orbitrap mass spectrometer founding., ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010), bidaux, gabriel, Instituts Hospitalo-Universitaires B - Organ ProtEction and ReplAcement - - OPeRa2010 - ANR-10-IBHU-0004 - IBHU - VALID, Department of Cardiology, Hospices Civils de Lyon (HCL), Institut National de la Sante et de la Recherche Medicale (Inserm), Lebanese University, Cedar program of Campus France [37303QA 2017-2018], IHU OPeRa within the program 'Investissements d'Avenir' [ANR-10-IBHU-004], Association de Spécialisation et d'orientation Scientifique, Council for Scientific Research and Lebanese University fellowship (CNRS-L) program, Eiffel scholarship program of excellence of Campus France, ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Sante, National Alliance for Life Sciences and Health), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Atropine, Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Mitochondrion, Mass Spectrometry, Mitochondria, Heart, Oxidative Phosphorylation, Mice, Nitroglycerin, 0302 clinical medicine, Papaverine, Myocytes, Cardiac, 10. No inequality, STAT3, Mice, Knockout, Cardiomyocytes, biology, Chemistry, Ischemia-reperfusion, Brain, Aminophylline, Cell biology, Mitochondria, [SDV] Life Sciences [q-bio], Drug Combinations, T-tubules, medicine.anatomical_structure, Liver, Phenobarbital, Cell fractionation, Cardiology and Cardiovascular Medicine, Signal Transduction, STAT3 Transcription Factor, Cell type, Myocardial Reperfusion Injury, Cell Line, 03 medical and health sciences, medicine, Animals, Molecular Biology, Transcription factor, Endoplasmic reticulum, Subcellular distribution, Rats, Mice, Inbred C57BL, 030104 developmental biology, Mitochondrial permeability transition pore, biology.protein, Nucleus, Mitochondria associated membranes
Abstract: International audience; The signal transducer and activator of transcription 3, STAT3, transfers cellular signals from the plasma membrane to the nucleus, acting as a signaling molecule and a transcription factor. Reports proposed an additional non-canonical role of STAT3 that could regulate the activity of complexes I and II of the electron transport chain and the opening of the mitochondrial permeability transition pore (PTP) after ischemia-reperfusion in various cell types. The native expression of STAT3 in heart mitochondria, together with a direct versus an indirect transcriptional role in mitochondrial functions, have been recently questioned. The objective of the present study was to investigate the cellular distribution of STAT3 in mouse adult cardiomyocytes under basal and stress conditions, along with assessing its presence and activity in cardiac mitochondria using structural and functional approaches. The analysis of the spatial distribution of STAT3 signal in the cardiomyocytes interestingly showed that it is transversely distributed along the T-tubules and in the nucleus. This distribution was neither affected by hypoxia nor by hypoxia/re-oxygenation conditions. Focusing on the mitochondrial STAT3 localization, our results suggest that serine-phosphorylated STAT3 (PS727-STAT3) and total STAT3 are detected in crude but not in pure mitochondria of mouse adult cardiomyocytes, under basal and ischemia-reperfusion conditions. The inhibition of STAT3, with a pre-validated non-toxic Stattic dose, had no significant effects on mitochondrial respiration, but a weak effect on the calcium retention capacity. Overall, our results exclusively reveal a unique cellular distribution of STAT3 in mouse adult cardiomyocytes, along the Ttubules and in nucleus, under different conditions. They also challenge the expression and activity of STAT3 in mitochondria of these cells under basal conditions and following ischemia-reperfusion. In addition, our results underline technical methods, complemental to cell fractionation, to evaluate STAT3 roles during hypoxia-reoxygenation and at the interface between nucleus and endoplasmic reticulum.
Published: 2019
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29. A narrative review of the pathophysiology of ischemic stroke in carotid plaques: a distinction versus a compromise between hemodynamic and embolic mechanism

Author: Emmanuelle Canet-Soulas, Antoine Millon, Valentin Crespy, Lucie Rascle, Laura Mechtouff, and Norbert Nighoghossian
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Cerebral arteries, Hemodynamics, General Medicine, Review Article on Carotid Artery Stenosis and Stroke-Prevention and Treatment Part II, medicine.disease, Pathophysiology, Pathogenesis, Stenosis, Internal medicine, medicine, Cardiology, cardiovascular diseases, Embolization, Thrombus, business, Stroke
Abstract: Atherosclerotic carotid artery stenosis causes about 10-20% of all ischemic strokes through two main mechanisms: hemodynamic impairment in case of significant stenosis and thromboembolism from an atherosclerotic plaque regardless of the degree of stenosis. The latter is the most frequent mechanism and appear to result from embolization from a vulnerable atherosclerotic plaque or acute occlusion of the carotid artery and propagation of thrombus distally. Downstream infarcts may occur in a territory of major cerebral artery or at the most distal areas between two territories of major cerebral arteries, the so-called watershed (WS), or border zone area. Although WS infarcts, especially deep WS infarct, were historically thought to be due to hemodynamic compromise, the role of microembolism has also been documented, both mechanisms may act synergistically to promote WS infarcts. Routine and more advanced imaging techniques may provide information on the underlying mechanism involved in ipsilateral ischemic stroke. A better understanding of ischemic stroke pathogenesis in carotid stenosis may limit the use of routine non-selective shunt, whose benefit-risk balance is debated, to patients with hemodynamic impairment. After reviewing existing evidence underpinning the contribution of the two mechanisms in downstream ischemic stroke and the various imaging techniques available to investigate them, we will focus on the pathogenesis of WS infarcts that remains debated.
Published: 2021
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30. TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.

Author: Claudia, Goettsch, Agnieszka, Strzelecka-Kiliszek, Laurence, Bessueille, Thibaut, Quillard, Laura, Mechtouff, Slawomir, Pikula, Emmanuelle, Canet-Soulas, Millan, Jose Luis, Caroline, Fonta, and David, Magne
Subjects: ATHEROSCLEROSIS, CALCIFICATION, ADENINE nucleotides, VITAMIN B6, ALKALINE phosphatase, ARTERIAL calcification
Abstract: Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP's functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo. [ABSTRACT FROM AUTHOR]
Published: 2022
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31. Magnetic resonance imaging biomarkers of exercise-induced improvement of oxidative stress and inflammation in the brain of old high-fat-fed ApoE−/−mice

Author: Jennifer Rieusset, Benoit Thézé, Emmanuelle Canet-Soulas, Alain Géloën, Hubert Vidal, Vincent Pialoux, Fabien Chauveau, David Patsouris, Erica N. Chirico, Vanessa Di Cataldo, and Cyril Martin
Subjects: medicine.medical_specialty, Physiology, Inflammation, Brain damage, 030204 cardiovascular system & hematology, medicine.disease_cause, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, In vivo, Internal medicine, medicine, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, medicine.disease, 3. Good health, Endocrinology, chemistry, Ageing, medicine.symptom, business, 030217 neurology & neurosurgery, Oxidative stress
Abstract: KEY POINTS Vascular brain lesions and atherosclerosis are two similar conditions that are characterized by increased inflammation and oxidative stress. Non-invasive imaging in a murine model of atherosclerosis showed vascular brain damage and peripheral inflammation. In this study, exercise training reduced magnetic resonance imaging-detected abnormalities, insulin resistance and markers of oxidative stress and inflammation in old ApoE-/- mice. Our results demonstrate the protective effect of exercise on neurovascular damage in the ageing brain of ApoE-/- mice. ABSTRACT Vascular brain lesions, present in advanced atherosclerosis, share pathological hallmarks with peripheral vascular lesions, such as increased inflammation and oxidative stress. Physical activity reduces these peripheral risk factors, but its cerebrovascular effect is less documented, especially by non-invasive imaging. Through a combination of in vivo and post-mortem techniques, we aimed to characterize vascular brain damage in old ApoE-/- mice fed a high-cholesterol (HC) diet with dietary controlled intake. We then sought to determine the beneficial effects of exercise training on oxidative stress and inflammation in the brain as a treatment option in an ageing atherosclerosis mouse model. Using in vivo magnetic resonance imaging (MRI) and biological markers of oxidative stress and inflammation, we evaluated the occurrence of vascular abnormalities in the brain of HC-diet fed ApoE-/- mice >70 weeks old, its association with local and systemic oxidative stress and inflammation, and whether both can be modulated by exercise. Exercise training significantly reduced both MRI-detected abnormalities (present in 71% of untrained vs. 14% of trained mice) and oxidative stress (lipid peroxidation, 9.1 ± 1.4 vs. 5.2 ± 0.9 μmol mg-1 ; P
Published: 2016
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32. AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

Author: Camille Verry, Awatef Allouch, Carolyn J. Anderson, Olivier Tillement, Cyrus Chargari, Nathalie Mignet, Benoit Larrat, Marc Janier, Jacqueline Sidi-Boumedine, Kevin M. Prise, Peter Fries, Bich-Thuy Doan, Erika Porcel, Fabien Rossetti, Jacques Balosso, Marie-Caline Abadjian, Dominique Ardail, Frédéric Boschetti, Yannick Crémillieux, Alexandre Detappe, Claire Rodriguez-Lafrasse, Ross Berbeco, Marie-Thérèse Aloy, Sébastien Mériaux, Vu Long Tran, Emmanuel L. Barbier, Sandrine Lacombe, Sandrine Dufort, Matteo Martini, Andreas Müller, Eric Deutsch, Karl T. Butterworth, Emmanuelle Canet-Soulas, Géraldine Le Duc, Franck Denat, Goran Angelovski, Guillaume Bort, Céline Frochot, Jean-Luc Perfettini, Eloise Thomas, Stéphane Roux, Tristan Doussineau, Muriel Barberi-Heyob, Michael J. Evans, François Lux, Charles Truillet, Stephen J. McMahon, Penelope Bouziotis, Thomas, Noémie, Formation, élaboration de nanomatériaux et cristaux (FENNEC), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), NH TherAguix SA [Meylan], Nano-H SAS, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CheMatech - Macrocycle Design Technologies, Max Planck Institute for Biological Cybernetics, Max-Planck-Gesellschaft, Dana-Farber Cancer Institute [Boston], Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinic for Diagnostic and Interventional Radiology, Saarland University Medical Center, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Center for Scientific Research 'Demokritos' (NCSR), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Réactions et Génie des Procédés (LRGP), Rayonnement synchrotron et Recherche Médicale, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), University of California [San Francisco] (UC San Francisco), University of California (UC), Université de Lyon, Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), PRISME (PRISME), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire de Lyon (IPNL), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Radiothérapie moléculaire (UMR 1030), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR), Institut de Recherche Biomédicale des Armées (IRBA), French Military Health Service Academy, École du Val de Grâce (EVDG), Service de Santé des Armées-Service de Santé des Armées, Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), University of California [San Francisco] (UCSF), University of California, Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), NH Theraguix, Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Equipe 6 : Rayonnement synchrotron et Recherche Médicale, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-[GIN] Grenoble Institut des Neurosciences, Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine), Ecole du Val-de-Grâce, UM Biochimie des Cancers et Biothérapies, CHU Grenoble-Institut de Biologie et Pathologie, Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut Galien Paris-Sud (IGPS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Mécanique et Technologie (LMT), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institute of Computer Science VI, Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Rhône-Alpes Research Program on Hadrontherapy, National French Hadrontherapy Centre - Etoile, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurorestoration Group, King‘s College London-Wolfson Centre for Age-related Diseases, Ciblage thérapeutique en Oncologie (EA3738), Unité Médicale d'Oncologie Moléculaire et Transfert (UMOMT), Hospices Civils de Lyon (HCL), Laboratoire des collisions atomiques et moléculaires (LCAM), Service d'oncologie-radiothérapie, Hôpital d'Instruction des Armées du Val de Grâce, Service de Santé des Armées, and European Synchrotron Radiation Facility (ESRF)
Subjects: Radiation-Sensitizing Agents, Gadolinium, medicine.medical_treatment, 02 engineering and technology, Review Article, Pharmacology, Theranostic Nanomedicine, Mice, 0302 clinical medicine, Melanoma, Brain Neoplasms, General Medicine, [CHIM.MATE]Chemical Sciences/Material chemistry, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 021001 nanoscience & nanotechnology, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Nuclear Medicine & Medical Imaging, Radiology Nuclear Medicine and imaging, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Toxicity, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Clinical Sciences, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, Enhanced permeability and retention effect, 03 medical and health sciences, SDG 3 - Good Health and Well-being, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Animals, Humans, Radiology, Nuclear Medicine and imaging, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Cancer, medicine.disease, Radiation therapy, Clinical trial, chemistry, Nanoparticles, business, Forecasting
Abstract: International audience; AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.
Published: 2019
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33. INFLAM - INFLAMmation in Brain and Vessels with Iron Nanoparticles and Cell Trafficking: A Multiscale Approach of Tissue Microenvironment, Iron Nanostructure and Iron Biotransformation

Author: N. Nighoghossian, Claire Corot, Marlène Wiart, Emmanuelle Canet-Soulas, Jean-Christophe Brisset, F. Gazeau, Y. Berthezène, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA), Université de Lyon (COMUE), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Guerbet, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, medicine.medical_specialty, magnetic nanoparticles, mice, [SDV]Life Sciences [q-bio], Cell, Biomedical Engineering, Biophysics, AMNP, Inflammation, 02 engineering and technology, ultrasmall superparamagnetic particles, tomography, 030218 nuclear medicine & medical imaging, neuroinflammation, 03 medical and health sciences, ischemic-stroke, 0302 clinical medicine, Engineering, Inflammation imaging, medicine, subacute, Stroke, Neuroinflammation, medicine.diagnostic_test, Bioorganic nanoparticles transformation, business.industry, Magnetic resonance imaging, 021001 nanoscience & nanotechnology, medicine.disease, Atherosclerosis, Acute stage, 3. Good health, medicine.anatomical_structure, uspio-enhanced mri, Ischemic stroke, focal ischemia, [SDV.IB]Life Sciences [q-bio]/Bioengineering, nanoparticles, oxide, Ultrasmall superparamagnetic iron oxide (USPIO), medicine.symptom, 0210 nano-technology, business, MRI
Abstract: International audience; Background: Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke. Contribution: We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects. Conclusion: This review presents the contribution of the collaborative research project under the "TecSan" grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. (C) 2018 Published by Elsevier Masson SAS on behalf of AGBM.
Published: 2018
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34. Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity

Author: Mury, P., Chirico, E. N., Mura, M., Millon, A., Emmanuelle Canet Soulas, Pialoux, V., Laboratoire de l'intégration, du matériau au système (IMS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: ischemic-heart-disease, function, coronary-artery-disease, c-reactive protein, double-knockout mice, nitric-oxide synthase, [SDV]Life Sciences [q-bio], age-related increase, cell-adhesion molecule-1, high-density-lipoprotein, intima-media thickness, improves endothelial, Sport Sciences
Abstract: Atherosclerosis, a complex cardiovascular disease, is a leading cause of mortality and morbidity worldwide. Oxidative stress and inflammation are both involved in the development of atherosclerotic plaque as they increase the biological processes associated with this pathology, such as endothelial dysfunction and macrophage recruitment and adhesion. Atherosclerotic plaque rupture leading to major ischemic events is the result of vulnerable plaque progression, which is a result of the detrimental effect of oxidative stress and inflammation on risk factors for atherosclerotic plaque rupture, such as intraplaque hemorrhage, neovascularization, and fibrous cap thickness. Thus, both are key targets for primary and secondary interventions. It is well recognized that chronic physical activity attenuates oxidative stress in healthy subjects via the improvement of antioxidant enzyme capacities and inflammation via the enhancement of anti-inflammatory molecules. Moreover, it was recently shown that chronic physical activity could decrease oxidative stress and inflammation in atherosclerotic patients. The aim of this review is to summarize the role of oxidative stress and inflammation in atherosclerosis and the results of therapeutic interventions targeting them in both preclinical and clinical studies. The effects of chronic physical activity on these two key processes are then reviewed in vulnerable atherosclerotic plaques in both coronary and carotid arteries.
Published: 2018

35. Exercise Does Not Protect against Peripheral and Central Effects of a High Cholesterol Diet Given Ad libitum in Old ApoE−/− Mice

Author: Benoit Thézé, Alain Géloën, Hubert Vidal, Jean-Baptiste Langlois, Vanessa Di Cataldo, Erica N. Chirico, Jennifer Rieusset, Violaine Hubert, Emmanuelle Canet-Soulas, Fabien Chauveau, Vincent Pialoux, Marlène Wiart, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Canet-Soulas, Emmanuelle, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire de France, University Claude Bernard Lyon 1, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: 0301 basic medicine, medicine.medical_specialty, Physiology, [SDV]Life Sciences [q-bio], physical activity, Inflammation, Context (language use), Brain damage, medicine.disease_cause, Blood–brain barrier, lcsh:Physiology, 03 medical and health sciences, Cerebral circulation, neuroinflammation imaging, 0302 clinical medicine, Insulin resistance, overfeeding, Physiology (medical), Internal medicine, medicine, atherosclerosis, oxidative stress, Original Research, computer.programming_language, 2. Zero hunger, lcsh:QP1-981, business.industry, sed, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, medicine.symptom, business, computer, 030217 neurology & neurosurgery, Oxidative stress
Abstract: International audience; Aim: Advanced atherosclerosis increases inflammation and stroke risk in the cerebral vasculature. Exercise is known to improve cardio-metabolic profiles when associated with a caloric restriction, but it remains debated whether it is still beneficial without the dietary control. The aim of this study was to determine both the peripheral and central effects of exercise training combined with a cholesterol-rich diet given ad libitum in old ApoE-/- mice. Methods: Forty-five-weeks old obese ApoE-/- mice fed with a high cholesterol diet ad libitum were divided into Exercise-trained (EX; running wheel free access) and Sedentary (SED) groups. Insulin tolerance and brain imaging were performed before and after the twelve-weeks training. Tissue insulin resistance, oxidative stress, and inflammation markers in plasma, aorta, and brain were then assessed. Results: In EX ApoE-/- mice, no beneficial effect of exercise was observed on weight, abdominal fat, metabolic parameters, oxidative stress, or inflammation compared to SED. Despite the regular exercise training in ApoE-/- EX mice (mean of 12.5 km/week during 12 weeks), brain inflammation imaging score was significantly associated with increased blood brain barrier (BBB) leakage evaluated by imaging follow-up (r2 = 0.87; p = 0.049) with a faster evolution compared to SED ApoE-/-mice. Conclusion: We conclude that in a context of high cardio-metabolic risk, exercise does not provide any protective effect in old ApoE-/- animals under high cholesterol diet given ad libitum. Peripheral (insulin sensitivity and oxidative/inflammatory status) but also central features (BBB preservation and protection against inflammation) did not show any benefits of exercise. Indeed, there was a fast induction of irreversible brain damage that was more pronounced in exercise-trained ApoE-/- mice.
Published: 2016
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36. Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates

Author: Lucie Sancey, Joao Piraquive, Vanessa Di Cataldo, Emmanuelle Canet-Soulas, Shady Kotb, Michaël Verset, François Lux, Olivier Tillement, Hugues Contamin, Franck Lamberton, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Cynbiose, CYNBIOSE, LABEX PRIMES of Lyon 1 University within the program 'Investissements d'Avenir' [ANR-11-LABX-0063, ANR-11-IDEX-0063], French National Research Agency (ANR) within the ANR Cyclops [ANR-15-CE17-0020], ANR-11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR-15-CE17-0020,CYCLOPS,CYCLOsporine A : effet neuroprotecteur dans un modèle Primate de Stroke en imagerie(2015), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-IDEX-0007-02/11-LABX-0063,PRIMES,Physique, Radiobiologie, Imagerie Médicale et Simulation(2011), ANR: Cyclops,ANR-15-CE17-0020, Kotb, Shady, Piraquive, Joao, Sancey, Lucie, Rayet, Béatrice, Physique, Radiobiologie, Imagerie Médicale et Simulation - - PRIMES2011 - ANR-11-LABX-0063 - LABX - VALID, CYCLOsporine A : effet neuroprotecteur dans un modèle Primate de Stroke en imagerie - - CYCLOPS2015 - ANR-15-CE17-0020 - AAPG2015 - VALID, and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: imagerie par résonance magnétique, Male, Primates, Cholesterol diet, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Gadolinium, chemistry.chemical_element, Contrast Media, Context (language use), 02 engineering and technology, 030204 cardiovascular system & hematology, primate, Diet, High-Fat, nanoparticule, Article, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Image Interpretation, Computer-Assisted, medicine, évaluation de la toxicité, Animals, Multidisciplinary, medicine.diagnostic_test, business.industry, athérosclérose, Magnetic resonance imaging, 021001 nanoscience & nanotechnology, Atherosclerosis, Magnetic Resonance Imaging, humanities, 3. Good health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, chemistry, Toxicity, Standard diet, Plaque imaging, Nanoparticles, Administration, Intravenous, Female, 0210 nano-technology, business
Abstract: In this article, we report the safety evaluation of gadolinium-based nanoparticles in nonhuman primates (NHP) in the context of magnetic resonance imaging (MRI) studies in atherosclerosis bearing animals and healthy controls. In healthy NHP, the pharmacokinetics and toxicity profiles demonstrated the absence of dose, time, and sex-effects, as well as a suitable tolerance of intravenous administration of the nanoparticles. We investigated their imaging properties for arterial plaque imaging in a standard diet or a high cholesterol diet NHP, and compared their characteristics with clinically applied Gd-chelate. This preliminary investigation reports the efficient and safe imaging of atherosclerotic plaques.
Published: 2016
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37. Markers of vulnerable plaques in non-human primates under atherogenic diet

Author: D. Ibarolla, A. Paturet, Emmanuelle Canet-Soulas, D. Le bars, André Sérusclat, F. Lavenne, J. Piraquive Agudelo, Alain Géloën, V. Di Cataldo, Michaël Verset, Hugues Contamin, Franck Lamberton, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CYNBIOSE, Institut Claude Bourgelat (ICLB), Département de Radiologie (LYON - Radio), CHU Lyon, ProdInra, Archive Ouverte, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Atherogenic diet, 0303 health sciences, business.industry, education, Physiology, social sciences, 030204 cardiovascular system & hematology, primate, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 03 medical and health sciences, régime alimentaire, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Medicine, animal vascular system, Cardiology and Cardiovascular Medicine, business, système cardiovasculaire, health care economics and organizations, 030304 developmental biology
Abstract: Markers of vulnerable plaques in non-human primates under atherogenic diet. Congress of the European-Atherosclerosis-Society (EAS)
Published: 2016

38. Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease

Author: Camille Faes, Erica N. Chirico, Vincent Pialoux, Emmanuelle Canet-Soulas, Cyril Martin, Philippe Connes, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Xanthine Oxidase, Anemia, Iron, [SDV]Life Sciences [q-bio], Hemoglobin, Sickle, Physical Therapy, Sports Therapy and Rehabilitation, Inflammation, Anemia, Sickle Cell, Heme, Disease, 030204 cardiovascular system & hematology, Nitric Oxide, medicine.disease_cause, Hemolysis, Sickle Cell Trait, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Orthopedics and Sports Medicine, Hypoxia, Exercise, ComputingMilieux_MISCELLANEOUS, Sickle cell trait, business.industry, NADPH Oxidases, Hypoxia (medical), medicine.disease, 3. Good health, Disease Models, Animal, Oxidative Stress, 030104 developmental biology, Hemoglobinopathy, Reperfusion Injury, Immunology, medicine.symptom, business, Reperfusion injury, Oxidative stress
Abstract: International audience; Sickle cell disease is a class of hemoglobinopathy in humans, which is the most common inherited disease in the world. Although complications of sickle cell disease start from polymerization of red blood cells during its deoxygenating phase, the oxidative stress resulting from the biological processes associated with this disease (ischaemic and hypoxic injuries, hemolysis and inflammation) has been shown to contribute to its pathophysiology. It is widely known that chronic exercise reduces oxidative stress in healthy people, mainly via improvement of antioxidant enzyme efficiency. In addition, recent studies in other diseases, as well as in sickle cell trait carriers and in a mouse model of sickle cell disease, have shown that regular physical activity could decrease oxidative stress. The purpose of this review is to summarize the role of oxidative stress in sickle cell disease and the effects of acute and chronic exercise on the pro-oxidant/antioxidant balance in sickle cell trait and sickle cell disease.
Published: 2016
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39. Molecular MRI of Atherosclerosis with USPIO

Author: Emmanuelle Canet-Soulas and Monica Sigovan
Subjects: Pathology, medicine.medical_specialty, Histology, Cell adhesion molecule, business.industry, Inflammation, Cell Biology, Applied Microbiology and Biotechnology, In vivo, Toxicity, medicine, Molecular mri, Platelet activation, medicine.symptom, Molecular imaging, business, Preclinical imaging
Abstract: Inflammation in atherosclerosis is a risk factor for plaque rupture and atherothrombosis. USPIO-enhanced MRI is capable of evaluating the inflammatory activity in vivo on a cellular as well as a sub-cellular level. This paper reviews the recent advances in USPIO-enhanced MRI of atherosclerotic plaque inflammation. Imaging strategies for evidentiating the presence of the USPIO label in plaques take advantage of the susceptibility effect induced by the nanoparticles in their surroundings to obtain a negative contrast (T2* weighted imaging) or a positive contrast (the White Maker and Susceptibility Gradient Mapping). Quantitative methods have more recently been adapted to in vivo imaging of USPIO in atherosclerotic plaques, and showed great promise in detecting treatment responses. When they are not taken up rapidly from blood by the reticulo-endothelial system (RES), USPIOs nanoparticles passively target inflammation in atherosclerosis by engulfment in intra-plaque phagocytic cells. This has been demonstrated in both animal models and human patients. However, by modifying the surface of coating materials, nanoparticles can actively target atherosclerosis molecular and cellular actors in animal models. The goal of molecular imaging of atherosclerotic plaques is to identify events in the early onset of the disease, as well as critical evolution to vulnerable plaques. USPIO agents are preferred as basis to develop targeted agents because of the ability to overcome the toxicity issue of long-term body residence of Gd-based agents, and their lower sensitivity based on their relaxivity properties. MRI agents capable of efficiently targeting oxidized LDL, cell adhesion molecules (VCAM-1, P-selectin, E-selection), apoptosis and activated platelets have been demonstrated in animal models. The use of these methodologies at the clinical level will depend on the availability and toxicity profiles of the agents, and will require standardized state of the art imaging techniques.
Published: 2012
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40. Positive contrast with therapeutic iron nanoparticles at 4.7 T

Author: Emmanuelle Canet-Soulas, Monica Sigovan, Delphine Charpigny, Achraf Al Faraj, Hatem Fessi, Misara Hamoudeh, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'automatique et de génie des procédés (LAGEP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, Biophysics, Contrast Media, Nanoparticle, Nanotechnology, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Mice, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Image Interpretation, Computer-Assisted, mental disorders, medicine, Animals, Computer Simulation, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Radiology, Nuclear Medicine and imaging, Magnetite Nanoparticles, Radiological and Ultrasound Technology, medicine.diagnostic_test, Phantoms, Imaging, ACL, Tumor therapy, Dextrans, Magnetic resonance imaging, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Image enhancement, Image Enhancement, Magnetic Resonance Imaging, Positive contrast, Feasibility Studies, Magnetic nanoparticles, Female, psychological phenomena and processes, 030217 neurology & neurosurgery, Gradient echo, Superparamagnetism
Abstract: The purpose of the study was to show the feasibility of a positive contrast technique GRadient echo Acquisition for Superparamagnetic particles with Positive contrast (GRASP), for a specific type of magnetic particles, designed for tumor treatment under MRI monitoring.A simulation study was performed to estimate field inhomogeneity intensities induced by increasing concentrations of particles at different static fields. The GRASP sequence was setup on a 4.7 T Bruker system during an in vitro study. Six mice, included in the in vivo study received particles in the left calf muscle and contrast enhancement values, were measured over three time points, for both negative and positive contrast images.Comparing values obtained by simulation at 1.5, 3, and 4.7 T, the strongest susceptibility effect was obtained at 4.7 T. Based on simulation and in vitro data, gradient settings were chosen for in vivo imaging. GRASP resulted in bright regions at and around the injection site, and higher enhancement values, compared to standard GRE imaging. Both contrasts were useful for longitudinal follow-up, with a faster decay over time for GRASP.The magnetic nanoparticles for drug delivery can be detected using positive contrast. Combining imaging sequences, i.e., negative contrast and susceptibility methods, increased imaging specificity of large magnetic particles and enabled their follow-up for theranostic applications.
Published: 2011
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41. M1-Activated Macrophages Migration, A Marker of Aortic Atheroma Progression

Author: Geneviève De Souza, Monica Sigovan, Emmanuelle Canet-Soulas, Hasan Alsaid, Norbert Nighoghossian, Zouher Majd, Serge Nataf, Amine Bessaad, Christine Ménager, Florence Lagarde, Jérôme Honnorat, Nicolas Provost, Imagerie et modélisation Vasculaires, Thoraciques et Cérébrales (MOTIVATE), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique de l'état condensé (LPEC), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sigovan, Monica, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Aortic arch, Pathology, medicine.medical_specialty, Apolipoprotein E2, Arteriosclerosis, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Aortic Diseases, Mice, Transgenic, Proinflammatory cytokine, Mice, In vivo, medicine.artery, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Animals, Macrophage, Radiology, Nuclear Medicine and imaging, Gene Knock-In Techniques, medicine.diagnostic_test, business.industry, Macrophages, Histology, Magnetic resonance imaging, General Medicine, Macrophage Activation, medicine.disease, Magnetic Resonance Imaging, Atheroma, Dynamic contrast-enhanced MRI, business, Biomarkers
Abstract: Background: M1-activated Macrophages (M1M) play a major role in atherosclerotic lesions of aortic arch, promoting proinflammatory response. In vivo trafficking of M1M in aortic plaques is therefore critical. Methods: M1M from bone marrow cell culture were magnetically labeled, using iron nanoparticles, intravenously injected and followed up with 3 day magnetic resonance imaging (MRI) in mice developing macrophage-laden atheroma (ApoE2 knock-in mice). M1M recruitment in aortic arch lesions was assessed both by MRI and histology. Results: In all ApoE2 knock-in mice injected with labeled cells, high resolution MRI showed localized signal loss regions in the thickened aortic wall, with a maximal effect at day 2 (―34% ± 7.3% P < 0.001 compared with baseline). This was confirmed with Prussian blue (iron) staining and corresponded to M1M (Major Histo-compatibility Complex II positive). Clear different intraplaque and adventitial dynamic distribution profiles of labeled cells were observed during the 3 days. Conclusion: M1M dynamic MRI is a promising marker to noninvasively assess the macrophage trafficking underlying aortic arch plaque progression.
Published: 2010
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42. Mise au point sur l’IRM haute résolution de la plaque carotidienne

Author: Norbert Nighoghossian, David Saloner, D. Gamondes, Loic Boussel, Philippe Douek, Emmanuelle Canet-Soulas, and Jean Michel Serfaty
Subjects: Pathology, medicine.medical_specialty, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Carotid arteries, Plaque composition, High resolution, Magnetic resonance imaging, medicine.disease, Stenosis, Carotid artery plaque, Medicine, Radiology, Nuclear Medicine and imaging, business, Nuclear medicine
Abstract: A third of cerebrovascular accidents are a complication from carotid artery plaque. In addition to the degree of stenosis, plaque composition and morphology are key elements in determining the probability of complication from the atherosclerotic plaque. High resolution MRI can characterize plaque composition and morphology and therefore help identify unstable plaque. The purpose of this review is to summarize recent concepts on unstable plaque and underlying inflammation. The signal characteristics of the different components of plaque on high resolution MRI then be reviewed. Finally, current morphological and functional criteria for unstable plaque will be discussed.
Published: 2010
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43. In vivo proton HR-MAS NMR metabolic profile of the freshwater cladoceran Daphnia magna

Author: Bernard Vollat, Florence Fauvelle, Danielle Graveron-Demilly, Emmanuelle Canet-Soulas, Andrei Bunescu, Jeanne Garric, and Irstea Publications, Migration
Subjects: [SDE] Environmental Sciences, chemistry.chemical_classification, Magnetic Resonance Spectroscopy, fungi, Daphnia magna, Fatty acid, Fresh Water, Biology, biology.organism_classification, Daphnia, Toxicology, Biochemistry, chemistry, In vivo, Metabolome, Animals, Proton spectra, Molecular Biology, reproductive and urinary physiology, Metabolic profile, Biotechnology
Abstract: The method concerning in vivo proton HR-MAS NMR metabolic profiling of the freshwater cladoceran Daphnia magna is presented. Viability tests of D. magna under different spinning rates were performed. All surviving daphnids after analysis have developed eggs and embryos like control animals. Better survival rate at the slowest rotation speed were observed. The maximum length of analysis during which the integrity of the daphnid is maintained was assessed. The recorded proton spectra of in vivo daphnia were attributed to lipids from the triglycerol category. Saturated and unsaturated omega-3 like fatty acid moieties of triacylglycerol were well identified. The relationship between physiological state of daphnids and lipid profile are discussed.
Published: 2010
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44. Effects of training and detraining on adiponectin plasma concentration and muscle sensitivity in lean and overweight men

Author: Caroline Gastebois, Jocelyne Drai, Stéphane Blanc, Audrey Bergouignan, Emmanuelle Canet-Soulas, Clément Villars, Etienne Lefai, Chantal Simon, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Division of Endocrinology, metabolism and diabetes, University of Colorado Anschutz [Aurora], Service d'Endocrinologie Diabete Nutrition, Université de Lyon, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Fondation Coeur et Arteres, University Hospital of Strasbourg, France, French National Agency for Research (PRNA), Centre National de la Recherche Scientifique (CNRS), and French Ministry of Higher Education and Research
Subjects: Muscle tissue, Male, medicine.medical_specialty, Physiology, Adipose tissue, 030209 endocrinology & metabolism, Plasma adiponectin, 030204 cardiovascular system & hematology, Overweight, 03 medical and health sciences, 0302 clinical medicine, Thinness, Physiology (medical), Internal medicine, Adiponectin receptors, medicine, Aerobic exercise, Humans, Orthopedics and Sports Medicine, Muscle, Skeletal, Exercise, Adiponectin, business.industry, Public Health, Environmental and Occupational Health, nutritional and metabolic diseases, General Medicine, Body weight, Adaptation, Physiological, Exercise Therapy, Endocrinology, medicine.anatomical_structure, Plasma concentration, [SDE]Environmental Sciences, Aerobic fitness, medicine.symptom, Sedentary Behavior, Training program, business, Multimeric forms, Physical Conditioning, Human
Abstract: To delineate the direct effect of physical activity on adiponectin metabolism, we investigated the impact of contrasted physical activity changes, independent of body mass changes, on adiponectin plasma concentration and muscle sensitivity in lean and overweight adult males. Eleven physically active lean men (70.6 ± 2.1 kg) were subjected to 1-month detraining; 9 sedentary lean men (73.1 ± 3.3 kg); and 11 sedentary overweight men (97.5 ± 3.0 kg) participated in a 2-month aerobic-exercise training program. Diet was controlled to maintain stable energy balance. Body composition, VO2peak, circulating adiponectin, adipose and muscle tissue adiponectin, muscle adiponectin receptors, and APPL1 mRNAs were measured before and after the interventions. At baseline, plasma high-molecular-weight adiponectin concentration was lower in both active lean (5.44 ± 0.58 µg/mL) and sedentary overweight (5.30 ± 1.06 µg/mL) than in sedentary lean participants (7.44 ± 1.06 µg/mL; both p
Published: 2016
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45. A new macromolecular paramagnetic MR contrast agent binds to activated human platelets

Author: Pascale Even, Eric Lancelot, Laure Bachelet, Charaf Zahir, Didier Letourneur, Ramin Bazeli, Jean Michel Serfaty, Hasan Alsaid, Emmanuelle Canet-Soulas, Frédéric Chaubet, Isabelle Bertholon, Claire Corot, Martine Jandrot-Perrus, and Ziad Touat
Subjects: Blood Platelets, Membrane Glycoproteins, Gadolinium, Molecular Mimicry, Electron Spin Resonance Spectroscopy, Contrast Media, chemistry.chemical_element, Platelet Activation, Ligand (biochemistry), In vitro, chemistry.chemical_compound, Sulfation, chemistry, Biochemistry, Heterocyclic Compounds, Organometallic Compounds, Biophysics, Humans, DOTA, Radiology, Nuclear Medicine and imaging, Platelet, Platelet activation, Macromolecule
Abstract: A new functionalized macromolecular magnetic resonance (MR) contrast agent has been developed from a carboxymethyldextran-Gd(DOTA) devoid of biospecificity. The functionalized contrast agent was synthesized in order to mimic PSGL-1, the main ligand of P-selectin, a glycoprotein mainly expressed on the surface of activated platelets. The starting compound, CM1, was first carboxymethylated by monochloroacetic acid leading to a series of 10 derivatives varying in their carboxymethyl content. CM8 derivative, with a degree of substitution in carboxymethyl of 0.84, was chosen for subsequent fluorolabeling and sulfation to give CM8FS. CM8FS has an average number molecular weight of 27 000 +/- 500 g/mol, a hydrodynamic radius of 5.7 +/- 0.2 nm and a high relaxivity (r(1) = 11.2/mM (Gd)/s at 60 MHz). Flow cytometry experiments on whole human blood or on isolated platelets evidenced in vitro a preferential binding of CM8FS on TRAP-activated human platelets. Interestingly, CM8FS did not bind to other blood cells or to resting platelets. Pellets of TRAP-activated human platelets have also been imaged in tubes with a 1.5 T MR imager. A MR signal was observed for activated platelets incubated with CM8FS. Altogether, these in vitro results evidenced the recognition of activated human platelets by a fluorescent paramagnetic contrast agent grafted with carboxyl and sulfate groups. This biomimetic approach associated with the versatile macromolecular platform appears promising for the development of new contrast agents for molecular imaging of activated platelets in cardiovascular diseases such as atherosclerosis and aneurysms.
Published: 2007
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46. Magnetic resonance imaging biomarkers of exercise-induced improvement of oxidative stress and inflammation in the brain of old high-fat-fed ApoE

Author: Erica N, Chirico, Vanessa, Di Cataldo, Fabien, Chauveau, Alain, Geloën, David, Patsouris, Benoît, Thézé, Cyril, Martin, Hubert, Vidal, Jennifer, Rieusset, Vincent, Pialoux, and Emmanuelle, Canet-Soulas
Subjects: Inflammation, Male, Mice, Knockout, Aging, Glutathione Peroxidase, Nitrates, Superoxide Dismutase, Tumor Necrosis Factor-alpha, Interleukin-1beta, Brain, Catalase, Diet, High-Fat, Cardiovascular, Magnetic Resonance Imaging, Mice, Inbred C57BL, Oxidative Stress, Apolipoproteins E, Cholesterol, Malondialdehyde, Physical Conditioning, Animal, Animals, Female, Aorta, Biomarkers, Nitrites
Abstract: Vascular brain lesions and atherosclerosis are two similar conditions that are characterized by increased inflammation and oxidative stress. Non-invasive imaging in a murine model of atherosclerosis showed vascular brain damage and peripheral inflammation. In this study, exercise training reduced magnetic resonance imaging-detected abnormalities, insulin resistance and markers of oxidative stress and inflammation in old ApoEVascular brain lesions, present in advanced atherosclerosis, share pathological hallmarks with peripheral vascular lesions, such as increased inflammation and oxidative stress. Physical activity reduces these peripheral risk factors, but its cerebrovascular effect is less documented, especially by non-invasive imaging. Through a combination of in vivo and post-mortem techniques, we aimed to characterize vascular brain damage in old ApoE
Published: 2015

47. Mesure sélective des temps de relaxation T2 des lipides intra et extramyocytaires chez le rat Zucker à 7 teslas

Author: Rachida Fissoune, Denis Grenier, André Briguet, and Emmanuelle Canet-Soulas
Subjects: General Chemical Engineering, General Chemistry
Abstract: Resume Differentes techniques ont ete utilisees pour determiner la concentration des lipides musculaires, mais elles necessitent des prelevements et elles ne permettent pas de quantifier avec precision les lipides intramyocellulaires (LIMC) et les lipides extramyocellulaires (LEMC). La spectroscopie proton RMN peut distinguer in vivo les deux types de lipides en se fondant sur la difference de susceptibilite magnetique liee a la forme des depots de LIMC et de LEMC. En revanche, la quantification de ces lipides reste difficile, compte tenu des largeurs de raies. La connaissance des temps de relaxation de ces deux types de lipides est donc importante pour optimiser cette quantification. L'objectif de cette etude est de mesurer les temps de relaxation transversale des LIMC et LEMC chez le rat Zucker a 7 teslas. Pour citer cet article : R. Fissoune et al., C. R. Chimie 9 (2006).
Published: 2006
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48. Real-time gating system for mouse cardiovascular MR imaging

Author: Latifa Fakri-Bouchet, André Briguet, Cédric Pasquier, Hasan Alsaid, Maher Sabbah, Odette Fokapu, and Emmanuelle Canet-Soulas
Subjects: Computer science, Noise reduction, Aorta, Thoracic, Gating, Signal, Electrocardiography, Mice, QRS complex, Nuclear magnetic resonance, Animals, Radiology, Nuclear Medicine and imaging, Computer vision, Passband, Digital signal processing, Mice, Knockout, Signal processing, business.industry, Heart, Signal Processing, Computer-Assisted, Magnetic Resonance Imaging, Mice, Inbred C57BL, Feasibility Studies, Artificial intelligence, business, Sensitivity (electronics), Algorithms
Abstract: Mouse cardiac MR gating using ECG is affected by the hostile MR environment. It requires appropriate signal processing and correct QRS detection, but gating software methods are currently limited. In this study we sought to demonstrate the feasibility of digital real-time automatically updated gating methods, based on optimizing a signal-processing technique for different mouse strains. High-resolution MR images of mouse hearts and aortic arches were acquired using a chain consisting of ECG signal detection, digital signal processing, and gating signal generation modeled using Simulink (The MathWorks, Inc., Natick, MA, USA). The signal-processing algorithms used were respectively low-pass filtering, nonlinear passband, and wavelet decomposition. Both updated and nonupdated gating signal generation methods were tested. Noise reduction was assessed by comparison of the ECG signal-to-noise ratio (SNR) before and after each processing step. Gating performance was assessed by measuring QRS detection accuracy before and after online trigger-level adjustments. Low-pass filtering with trigger-level adjustment gave the best performance for mouse cardiovascular imaging using gradient-echo (GE), spin-echo (SE), and fast SE (FSE) sequences with minimum induced delay and maximum gating efficiency (99% sensitivity and R-peak detection). This simple digital gating interface will allow various gating strategies to be optimized for cardiovascular MR explorations in mice.
Published: 2006
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49. The Src Homology and Collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development

Author: Nathalie Niederhoffer, Michael Gotthardt, Jérôme Terrand, Véronique Bruban, Frank Kober, Emmanuelle Canet-Soulas, Mohamed Mlih, Sophie Martin, Rachel L. Matz, Laurent Monassier, Philippe Boucher, Michael H. Radke, Francisco Abt-Jijon, Lionel Host, Nadia Messaddeq, Monique Bernard, Laboratoire de Biophotonique et Pharmacologie - UMR 7213 (LBP), Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))
Subjects: Src Homology 2 Domain-Containing, Transforming Protein 1, Receptor, ErbB-3, Cell Survival, [SDV]Life Sciences [q-bio], Myocytes, Smooth Muscle, Aucun, Aorta, Thoracic, Blood Pressure, Mice, Transgenic, 030204 cardiovascular system & hematology, Biochemistry, Receptor tyrosine kinase, Dystrophin, Mice, Plasma Membrane Calcium-Transporting ATPases, 03 medical and health sciences, 0302 clinical medicine, Animals, Myocytes, Cardiac, RNA, Small Interfering, Molecular Biology, Alleles, Costamere, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Microscopy, Confocal, biology, Gene Expression Regulation, Developmental, Signal transducing adaptor protein, Heart, Molecular Bases of Disease, Cell Biology, Costameres, Magnetic Resonance Imaging, Rats, 3. Good health, Cell biology, Phenotype, Shc Signaling Adaptor Proteins, Echocardiography, Cardiovascular and Metabolic Diseases, biology.protein, Neuregulin, Signal transduction, Gene Deletion, Proto-oncogene tyrosine-protein kinase Src
Abstract: Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca(2+)/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere.
Published: 2015

50. Low WSS Induces Intimal Thickening, while Large WSS Variation and Inflammation Induce Medial Thinning, in an Animal Model of Atherosclerosis

Author: Emmanuelle Canet-Soulas, Monica Sigovan, Antoine Millon, David Patsouris, Nicolas Provost, Zouher Majd, Vanessa Louzier, André Sérusclat, Jean-Louis Mathevet, Loic Boussel, Christian Paquet, Alain Géloën, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hémostase, Inflammation et sepsis (EA 4609), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Hopital Cardio-Thoracique et Vasculaire Louis Pradel, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: Vasculitis, Pathology, medicine.medical_specialty, Endothelium, Swine, [SDV]Life Sciences [q-bio], Hypercholesterolemia, lcsh:Medicine, Hemodynamics, Inflammation, Carotid Intima-Media Thickness, medicine, Eccentric, Animals, lcsh:Science, Phagocytes, Multidisciplinary, medicine.diagnostic_test, business.industry, lcsh:R, Magnetic resonance imaging, medicine.disease, Atherosclerosis, Biomechanical Phenomena, Stenosis, medicine.anatomical_structure, Carotid Arteries, Cuff, Angiography, cardiovascular system, Swine, Miniature, lcsh:Q, Endothelium, Vascular, medicine.symptom, business, Research Article
Abstract: International audience; OBJECTIVE: Atherosclerotic plaque development in the arterial wall is the result of complex interaction between the wall's endothelial layer and blood hemodynamics. However, the interaction between hemodynamic parameters and inflammation in plaque evolution is not yet fully understood. The aim of the present study was to investigate the relation between wall shear stress (WSS) and vessel wall inflammation during atherosclerotic plaque development in a minipig model of carotid stenosis. METHODS: A surgical procedure was performed to create left common carotid artery stenosis by placement of a perivascular cuff in minipigs under atherogenic diet. Animals were followed up on 3T MRI, 1 week after surgery and 3, 6, and 8 months after initiation of the diet. Computational fluid dynamics simulation estimated WSS distribution for the first imaging point. Vascular geometries were co-registered for direct comparison of plaque development and features (Gadolinium- and USPIO-Contrast Enhanced MRI, for permeability and inflammation respectively) with the initial WSS. Histological analysis was performed and sections were matched to MR images, based on spatial landmarks. RESULTS: Vessel wall thickening, permeability and inflammation were observed distally from the stenosis. They were eccentric and facing regions of normal wall thickness. Histological analysis confirmed eccentric plaque formation with lipid infiltration, intimal thickening and medial degradation. High phagocytic activity in the stenosis region was co-localized with high WSS, corresponding to intense medial degradation observed on histology samples. CONCLUSION: Lower WSS promotes atherosclerotic plaque development distal to an induced stenosis. Vascular and perivascular inflammation locations were predominant in the high WSS stenosis segment, where medial thinning was the major consequence.
Published: 2015
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