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10 results on '"European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN)"'

1. Microvascular MRI and Unsupervised Clustering Yields Histology-Resembling Images in Two Rat Models of Glioma

Author

Régine Farion, Nicolas Coquery, Chantal Rémy, Olivier François, Emmanuel L. Barbier, Benjamin Lemasson, Clément Debacker, 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), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, 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)-Bruker Biospin MRI, Bruker Biospin MRI-Bruker Biospin MRI, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), This work has been partially supported by the LabExPERSYVAL-Lab(ANR-11-LABX-0025-01), ANR-11-LABX-0025,PERSYVAL-lab,Systemes et Algorithmes Pervasifs au confluent des mondes physique et numérique(2011), Francois, Olivier, Laboratoires d'excellence - Systemes et Algorithmes Pervasifs au confluent des mondes physique et numérique - - PERSYVAL-lab2011 - ANR-11-LABX-0025 - LABX - VALID, Territoires, économie, enjeux sociétaux [?-2015] (LARHRA TEES [?-2015]), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 [2003-2015] (LARHRA [2003-2015]), Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 [2011-2015] (TIMC [2011-2015]), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-IMAG-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Biologie Computationnelle et Mathématique [?-2015] (TIMC-BCM [?-2015]), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-IMAG-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-IMAG-Institut polytechnique de Grenoble - Grenoble Institute of Technology [2007-2019] (Grenoble INP [2007-2019])-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), [GIN] Grenoble Institut des Neurosciences, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Bruker Biospin MRI, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), and ANR-11-LABX-0025-01,PERSYVAL-lab,Systèmes et Algorithmes Pervasifs au confluent des mondes physique et numérique(2011)

Subjects
Male, Pathology, medicine.medical_specialty, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Text mining, Region of interest, Cell Line, Tumor, Glioma, Image Processing, Computer-Assisted, medicine, Animals, Cluster Analysis, Effective diffusion coefficient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, medicine.diagnostic_test, Brain Neoplasms, business.industry, Brain, Discriminant Analysis, Histology, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Rats, Inbred F344, Rats, Neurology, Cerebral blood flow, Microvessels, Original Article, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Neoplasm Transplantation, 030217 neurology & neurosurgery, Preclinical imaging
Abstract

International audience; Imaging heterogeneous cancer lesions is a real challenge. For diagnosis, histology often remains the reference, but it is widely acknowledged that biopsies are not reliable. There is thus a strong interest in establishing a link between clinical in vivo imaging and the biologic properties of tissues. In this study, we propose to construct histology-resembling images based on tissue microvascularization, a magnetic resonance imaging (MRI) accessible source of contrast. To integrate the large amount of information collected with microvascular MRI, we combined a manual delineation of a spatial region of interest with an unsupervised, model-based cluster analysis (Mclust). This approach was applied to two rat models of glioma (C6 and F98). Six MRI parameters were mapped: apparent diffusion coefficient, vessel wall permeability, cerebral blood volume fraction, cerebral blood flow, tissular oxygen saturation, and cerebral metabolic rate of oxygen. Five clusters, defined by their MRI features, were found to correspond to specific histologic features, and revealed intratumoral spatial structures. These results suggest that the presence of a cluster within a tumor can be used to assess the presence of a tissue type. In addition, the cluster composition, i.e., a signature of the intratumoral structure, could be used to characterize tumor models as histology does.

Published
2014
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2. Impact of manganese on primary hippocampal neurons from rodents

Author

Daoust, Alexia, Saoudi, Yasmina, Brocard, Jacques, Collomb, Nora, Batandier, Cécile, Bisbal, Mariano, Salomé, Murielle, Andrieux, Annie, Bohic, Sylvain, Barbier, Emmanuel, 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), INSERM U836, équipe 1, Physiopathologie du cytosquelette, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), Région Rhône-Alpes - Cluster HVN., Dojat, Michel, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Neurons, Time Factors, Dose-Response Relationship, Drug, Otras Ciencias Biológicas, hippocampal neurons, Spectrometry, X-Ray Emission, MEMRI, Phosphorus, Hippocampus, Trace Elements, Ciencias Biológicas, mitochondria, Mice, Neuroblastoma, Zinc, hippocampalneurons, manganese, Animals, X-ray synchrotron, Calcium, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cells, Cultured, CIENCIAS NATURALES Y EXACTAS
Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo tract tracing or functional imaging of the central nervous system. However Mn2+ may be toxic at high levels. In this study, we addressed the impact of Mn2+ on mouse hippocampal neurons (HN) and neuron-like N2a cells in culture, using several approaches. Both HN and N2a cells not exposed to exogenous MnCl2 were shown by synchrotron X-ray fluorescence to contain 5 mg/g Mn. Concentrations of Mn2+ leading to 50% lethality (LC50) after 24 h of incubation were much higher for N2a cells (863 mM) than for HN (90 mM). The distribution of Mn2+ in both cell types exposed to Mn2+ concentrations below LC50 was perinuclear whereas that in cells exposed to concentrations above LC50 was more diffuse, suggesting an overloading of cell storage/detoxification capacity. In addition, Mn2+ had a cell-type and dose-dependent impact on the total amount of intracellular P, Ca, Fe and Zn measured by synchrotron X-ray fluorescence. For HN neurons, immunofluorescence studies revealed that concentrations of Mn2+ below LC50 shortened neuritic length and decreased mitochondria velocity after 24 h of incubation. Similar concentrations of Mn2+ also facilitated the opening of the mitochondrial permeability transition pore in isolated mitochondria from rat brains. The sensitivity of primary HN to Mn2+ demonstrated here supports their use as a relevant model to study Mn2+-induced neurotoxicity. Fil: Daoust, Alexia. Inserm; Francia. Université Grenoble Alpes. Grenoble; Francia Fil: Saoudi, Yasmina. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia Fil: Brocard, Jacques. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia Fil: Collomb, Nora. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia Fil: Batandier, Cecile. Laboratoire de Bioénergétique. Grenoble; Francia Fil: Bisbal, Mariano. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Salomé, Murielle. European Synchrotron Radiation Facility. Grenoble; Francia Fil: Andrieux, Annie. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia Fil: Bohic, Sylvain. European Synchrotron Radiation Facility. Grenoble; Francia. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia Fil: Barbier , Emmanuel. Université Grenoble Alpes. Grenoble; Francia. Inserm; Francia

Published
2014
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3. Neuronal transport defects of the MAP6 KO mouse - a model of schizophrenia - and alleviation by Epothilone D treatment, as observed using MEMRI

Author

Sylvain Bohic, Annie Andrieux, Yasmina Saoudi, Emmanuel L. Barbier, Alexia Daoust, Jean-Christophe Deloulme, Clément Debacker, Sylvie Gory-Fauré, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, 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), European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, 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)-Bruker Biospin MRI, Bruker Biospin MRI-Bruker Biospin MRI, ANR-10-BLAN-1202,CBioS,Fonctions cellulaires des protéines STOP : vers une compréhension fonctionnelle et moléculaire du rôle des microtubules dans la transmission synaptique et l'organisation neuronale(2010), European Project, Andrieux, Annie, BLANC - Fonctions cellulaires des protéines STOP : vers une compréhension fonctionnelle et moléculaire du rôle des microtubules dans la transmission synaptique et l'organisation neuronale - - CBioS2010 - ANR-10-BLAN-1202 - BLANC - VALID, Région Rhône-Alpes - Cluster HVN, and INCOMING

Subjects
medicine.medical_specialty, Cognitive Neuroscience, Contrast Media, MEMRI, Neurotransmission, Somatosensory system, Synaptic Transmission, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Internal medicine, medicine, Animals, Humans, MAP6, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuronal transport, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Manganese, medicine.diagnostic_test, Chemistry, Magnetic resonance imaging, Somatosensory Cortex, Magnetic Resonance Imaging, Tubulin Modulators, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Treatment Outcome, Neurology, Epothilones, Synaptic plasticity, Axoplasmic transport, Schizophrenia, Epothilone D, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Neuronal tract
Abstract

International audience; The MAP6 (microtubule-associated protein 6) KO mouse is a microtubule-deficient model of schizophrenia that exhibits severe behavioral disorders that are associated with synaptic plasticity anomalies. These defects are alleviated not only by neuroleptics, which are the gold standard molecules for the treatment of schizophrenia, but also by Epothilone D (Epo D), which is a microtubule-stabilizing molecule. To compare the neuronal transport between MAP6 KO and wild-type mice and to measure the effect of Epo D treatment on neuronal transport in KO mice, MnCl2 was injected in the primary somatosensory cortex. Then, using manganese-enhanced magnetic resonance imaging (MEMRI), we followed the propagation of Mn(2+) through axonal tracts and brain regions that are connected to the somatosensory cortex. In MAP6 KO mice, the measure of the MRI relative signal intensity over 24h revealed that the Mn(2+) transport rate was affected with a stronger effect on long-range and polysynaptic connections than in short-range and monosynaptic tracts. The chronic treatment of MAP6 KO mice with Epo D strongly increased Mn(2+) propagation within both mono- and polysynaptic connections. Our results clearly indicate an in vivo deficit in neuronal Mn(2+) transport in KO MAP6 mice, which might be due to both axonal transport defects and synaptic transmission impairments. Epo D treatment alleviated the axonal transport defects, and this improvement most likely contributes to the positive effect of Epo D on behavioral defects in KO MAP6 mice.

Published
2014
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4. Copper pathology in vulnerable brain regions in Parkinson's disease.: Copper pathology in PD

Author

Davies, Katherine, Bohic, Sylvain, Carmona, Asunción, Ortega, Richard, Cottam, Veronica, Hare, Dominic, Finberg, John, Reyes, Stefanie, Halliday, Glenda, Mercer, Julian, Double, Kay, Neuroscience Research Australia (NeuRA), School of Medical Sciences, Faculty of Medicine, University of New South Wales [Sydney] (UNSW), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-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), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Elemental Bio-imaging Facility, University of Technology Sydney (UTS), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Faculty of Medicine, Technion - Israel Institute of Technology [Haifa], Centre for Cellular and Molecular Biology, Deakin University, Melbourne, Discipline of Biomedical Sciences, The University of Sydney, and Serduc, Raphael

Subjects
nervous system, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

International audience; Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.

Published
2014
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5. Copper pathology in vulnerable brain regions in Parkinson's disease.: Copper pathology in PD

Author

Davies, Katherine, Bohic, Sylvain, Carmona, Asunción, Ortega, Richard, Cottam, Veronica, Hare, Dominic, Finberg, John, Reyes, Stefanie, Halliday, Glenda, Mercer, Julian, Double, Kay, Neuroscience Research Australia (NeuRA), School of Medical Sciences, Faculty of Medicine, University of New South Wales [Sydney] (UNSW), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-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), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Elemental Bio-imaging Facility, University of Technology Sydney (UTS), The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Faculty of Medicine, Technion - Israel Institute of Technology [Haifa], Centre for Cellular and Molecular Biology, Deakin University, Melbourne, Discipline of Biomedical Sciences, and The University of Sydney

Subjects
nervous system, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract

International audience; Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder.

Published
2014
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6. Synchrotron microbeam radiation therapy induces hypoxia in intracerebral gliosarcoma but not in the normal brain

Author

Emmanuel L. Barbier, Audrey Bouchet, Benjamin Lemasson, Elke Bräuer-Krisch, Nicolas Coquery, Jean A. Laissue, Claire Rome, Céline Le Clec'h, Emmanuel Brun, Raphaël Serduc, Chantal Rémy, Marine Potez, Geraldine LeDuc, Thomas Christen, Anaïck Moisan, INSERM U836, équipe 7, Nanomédecine et cerveau, European Synchrotron Radiation Facility (ESRF)-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), 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), European Synchrotron Radiation Facility (ESRF), Pathology Institute, University of Bern, Faculty of Physics, Ludwig Maximilians University, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, Conseil Régional Rhône-Alpes, Ligue contre le cancer, comité de la Drôme, Association pour la recherche contre le cancer, Ludwig-Maximilians-Universität München (LMU), Ludwig-Maximilians University [Munich] (LMU), and Serduc, Raphael

Subjects
Pathology, medicine.medical_specialty, Gliosarcoma, Synchrotron Microbeam Radiation Therapy, Brain Tumors, vessel radiation responses, X-Ray Therapy, Tumor vasculature, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Vessel density, Microbeam radiation therapy, medicine, Animals, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Glucose Transporter Type 1, medicine.diagnostic_test, Tumor hypoxia, Brain Neoplasms, business.industry, Brain, Magnetic resonance imaging, Hematology, Oxygenation, 9l gliosarcoma, medicine.disease, Magnetic Resonance Imaging, Rats, 3. Good health, Oxygen, Oncology, Oxygen Saturation, 030220 oncology & carcinogenesis, Rat, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nuclear medicine, business, Synchrotrons, MRI
Abstract

International audience; PURPOSE: Synchrotron microbeam radiation therapy (MRT) is an innovative irradiation modality based on spatial fractionation of a high-dose X-ray beam into lattices of microbeams. The increase in lifespan of brain tumor-bearing rats is associated with vascular damage but the physiological consequences of MRT on blood vessels have not been described. In this manuscript, we evaluate the oxygenation changes induced by MRT in an intracerebral 9L gliosarcoma model. METHODS: Tissue responses to MRT (two orthogonal arrays (2×400Gy)) were studied using magnetic resonance-based measurements of local blood oxygen saturation (MR_SO2) and quantitative immunohistology of RECA-1, Type-IV collagen and GLUT-1, marker of hypoxia. RESULTS: In tumors, MR_SO2 decreased by a factor of 2 in tumor between day 8 and day 45 after MRT. This correlated with tumor vascular remodeling, i.e. decrease in vessel density, increases in half-vessel distances (×5) and GLUT-1 immunoreactivity. Conversely, MRT did not change normal brain MR_SO2, although vessel inter-distances increased slightly. CONCLUSION: We provide new evidence for the differential effect of MRT on tumor vasculature, an effect that leads to tumor hypoxia. As hypothesized formerly, the vasculature of the normal brain exposed to MRT remains sufficiently perfused to prevent any hypoxia.

Published
2013
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7. Manganese enhanced MRI in rat hippocampus: A correlative study with synchrotron X-ray microprobe

Author

Sylvain Bohic, Emmanuel L. Barbier, Alexia Daoust, INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, 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), Neuro-imagerie fonctionnelle et métabolique (ANTE-INSERM U836, équipe 5), European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), Région Rhône-Alpes Cluster HVN., and Serduc, Raphael

Subjects
Microprobe, Metabolic Clearance Rate, hippocampus, Cognitive Neuroscience, Iron, Magnesium Chloride, chemistry.chemical_element, Hippocampus, Contrast Media, MEMRI, Manganese, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, In vivo, medicine, Manganism, Animals, X-ray synchrotron, Tissue Distribution, rat, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Chemistry, Dentate gyrus, Magnetic resonance imaging, X-Ray Microtomography, medicine.disease, Magnetic Resonance Imaging, Rats, Zinc, Neurology, Hippocampal Fissure, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 030217 neurology & neurosurgery, Synchrotrons, MRI
Abstract

International audience; Manganese enhanced MRI (MEMRI) offers many possibilities such as tract tracing and functional imaging in vivo. Mn is however neurotoxic and may induce symptoms similar to those associated with Parkinson's disease (manganism). The mechanisms of Mn-induced neurotoxicity are not clear. In this study, we combine synchrotron X-ray fluorescence microprobe (SR-XRF) and MEMRI techniques to investigate spatial distribution of Mn within the rat hippocampus and how Mn interacts with Ca, Fe and Zn at a cellular level. Images were acquired in the rat hippocampus (n=23) and using two injection routes: intra-cerebral (MnCl(2): 50mM, 10μL) and intra-peritoneal (MnCl(2): 100mM, 30mg/kg). For both injection routes, Mn is found in dentate gyrus and in CA3: control: 2.5±1.6, intra-peritoneal: 5.0±2.4, and intra-cerebral: 25.1±9.2μg/g. Mn follows Zn distribution and has a negative impact on the total amount of Zn and Fe. The Mn-enhanced MRI contrast is well correlated with the total Mn amount measured with SR-XRF (R(2)=0.93; p

Published
2012
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8. Biomedical applications of the ESRF synchrotron-based microspectroscopy platform

Author

Jean Susini, Marine Cotte, Sylvain Bohic, Barbara Fayard, Markus Kuehbacher, Gema Martínez-Criado, Rémi Tucoulou, Peter Cloetens, Murielle Salomé, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-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), European Synchrotron Radiation Facility (ESRF), Centre de recherche et de restauration des musées de France (C2RMF), Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture et de la Communication (MCC), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Department of Molecular Trace Element Research in the Life Sciences, Hahn-Meitner-Institut, National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725), Neuroscience Research Australia, University of New South Wales, National Health, Medical Research Council of Australia, Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Serduc, Raphael

Subjects
Chemical imaging, Male, BALB 3T3 Cells, 02 engineering and technology, 01 natural sciences, PC12 Cells, law.invention, MESH: Hepatocytes, Mice, MESH: Melanins, Structural Biology, law, Microscopy, Spectroscopy, Fourier Transform Infrared, MESH: Dopaminergic Neurons, MESH: Animals, Metal ions, MESH: Phosphorus, MESH: Spermatozoa, MESH: BALB 3T3 Cells, Phosphorus, 021001 nanoscience & nanotechnology, Spermatozoa, Synchrotron, On cells, X ray microprobe, Metals, Microspectrophotometry, X-ray spectroscopy, MESH: Synchrotrons, Nanomedicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, MESH: Microspectrophotometry, 0210 nano-technology, X-ray microprobe, Materials science, MESH: Rats, Biomedical Technology, MESH: Manganese, Nanotechnology, MESH: Spectroscopy, Fourier Transform Infrared, MESH: X-Rays, Animals, Humans, MESH: PC12 Cells, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Mice, Melanins, Manganese, MESH: Metals, MESH: Humans, Dopaminergic Neurons, X-Rays, 010401 analytical chemistry, MESH: Male, 0104 chemical sciences, Rats, MESH: France, Chemical sensitivity, MESH: Potassium, Hepatocytes, Potassium, Cell, MESH: Biomedical Technology, Synchrotrons
Abstract

International audience; Very little is known about the sub-cellular distribution of metal ions in cells. Some metals such as zinc, copper and iron are essential and play an important role in the cell metabolism. Dysfunctions in this delicate housekeeping may be at the origin of major diseases. There is also a prevalent use of metals in a wide range of diagnostic agents and drugs for the diagnosis or treatment of a variety of disorders. This is becoming more and more of a concern in the field of nanomedicine with the increasing development and use of nanoparticles, which are suspected of causing adverse effects on cells and organ tissues. Synchrotron-based X-ray and Fourier-transformed infrared microspectroscopies are developing into well-suited sub-micrometer analytical tools for addressing new problems when studying the role of metals in biology. As a complementary tool to optical and electron microscopes, developments and studies have demonstrated the unique capabilities of multi-keV microscopy: namely, an ultra-low detection limit, large penetration depth, chemical sensitivity and three-dimensional imaging capabilities. More recently, the capabilities have been extended towards sub-100nm lateral resolutions, thus enabling sub-cellular chemical imaging. Possibilities offered by these techniques in the biomedical field are described through examples of applications performed at the ESRF synchrotron-based microspectroscopy platform (ID21 and ID22 beamlines).

Published
2012
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9. Efficacy of intracerebral delivery of Carboplatin in combination with photon irradiation for treatment of F98 glioma-bearing rats

Author

Rousseau, Julia, Barth, Rolf, Moeschberger, Melvin, Elleaume, Hélène, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-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), Department of Pathology, Ohio State University [Columbus] (OSU), and R.F.B. acknowledges the support of N.I.H. grant 1-R01-CA09845 and the Department of Pathology and a Research Investment Fund grant from The Ohio State University College of Medicine.

Subjects
MESH: Combined Modality Therapy, MESH: Photons, MESH: Rats, MESH: Infusion Pumps, MESH: Rats, Inbred F344, MESH: Random Allocation, intracerebral delivery, MESH: Male, F98 rat glioma, MESH: Glioma, MESH: Carboplatin, MESH: Survival Analysis, carboplatin, MESH: Brain Neoplasms, MESH: Antineoplastic Agents, MESH: Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], osmotic pumps, neoplasms, radiotherapy
Abstract

International audience; PURPOSE: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. METHODS AND MATERIALS: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. RESULTS: Untreated rats had a mean survival time (MST) +/- SE of 23 +/- 1 days, compared with 44 +/- 3 days for X-irradiated animals and 69 +/- 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 +/- 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. CONCLUSIONS: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

Published
2009
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10. Efficacy of intracerebral delivery of Carboplatin in combination with photon irradiation for treatment of F98 glioma-bearing rats.: Efficacy of radiotherapy combined with prolonged i.c. delivery of carboplatin against F98 rat-glioma

Author

Rousseau, Julia, Barth, Rolf, Moeschberger, Melvin, Elleaume, Hélène, Serduc, Raphael, INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-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), Department of Pathology, Ohio State University [Columbus] (OSU), and R.F.B. acknowledges the support of N.I.H. grant 1-R01-CA09845 and the Department of Pathology and a Research Investment Fund grant from The Ohio State University College of Medicine.

Subjects
MESH: Combined Modality Therapy, MESH: Photons, MESH: Rats, MESH: Infusion Pumps, MESH: Rats, Inbred F344, MESH: Random Allocation, intracerebral delivery, MESH: Male, F98 rat glioma, MESH: Glioma, MESH: Carboplatin, MESH: Survival Analysis, carboplatin, MESH: Brain Neoplasms, MESH: Antineoplastic Agents, MESH: Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], osmotic pumps, neoplasms, radiotherapy
Abstract

International audience; PURPOSE: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. METHODS AND MATERIALS: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. RESULTS: Untreated rats had a mean survival time (MST) +/- SE of 23 +/- 1 days, compared with 44 +/- 3 days for X-irradiated animals and 69 +/- 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 +/- 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. CONCLUSIONS: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

Published
2009
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