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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. Mélanges de lois de Student multivariées généralisées : application à la caractérisation de tumeurs par IRM multiparamétrique

Author

Arnaud, Alexis, Forbes, Florence, Coquery, Nicolas, Barbier, Emmanuel, Lemasson, Benjamin, Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), 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 5, Neuroimagerie fonctionnelle et perfusion cérébrale, European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), NeuroImagerie Fonctionnelle et Perfusion Cérébrale, [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), and Forbes, Florence

Subjects
[STAT.AP]Statistics [stat]/Applications [stat.AP], [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, melange de lois, tumeurs, [SDV] Life Sciences [q-bio], [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], algorithme EM, Statistiques, loi de Students multivariées, cerveau, mélange de lois, IRM multiparamétrique, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], IRM
Abstract

National audience; Nous présentons une méthode statistique de classification de données IRM multiparamétriques permettant la détection de valeurs atypiques et la réalisation d'un dictionnaire de signatures de tumeurs. Cette approche cherche à rassembler les observations en classes issues de lois de Student généralisées. Cela permet d'attribuer un poids à chaque observation dans chaque dimension de façon à pondérer l'influence des valeurs atypiques sur la forme des groupes. Des rats porteurs de gliomes 9L (n=5), C6 (provenant de deux laboratoires ; n=6 et 13), et F98 (n=13) ont été imagés par IRM multiparamétrique (coefficient de diffusion apparent, volume et débit sanguin cérébral, perméabilité des vaisseaux, et taux d'oxygénation des tissus). Des régions d'intérêts (ROI : 1 tumeur, 2 saines) ont été manuellement délimitées sur les images anatomiques, puis reportées sur les cartes paramétriques. Les voxels de toutes les ROI ont été rassemblés et classifiés, à l’aide d’un mélange de lois de Student multivariées généralisées, de façon à regrouper les pixels présentant des caractéristiques micro-vasculaires similaires. Le nombre de classes est obtenu par minimisation du critère d'information bayésien.La classification que nous avons obtenue est plus précise celle précédemment publiée (moyennes moins élevées et les variances réduites). Nous utilisons la proportion en classe au sein d'une ROI pour déduire la signature de chaque ROI. Toutes les ROI saines présentent une signature similaire : ceci permet de détecter un rat atypique. Au contraire, les ROI tumeurs sont très dissemblables (même pour les deux C6). Nos résultats montrent qu'il est possible de discriminer automatiquement les tissus sains des tissus tumoraux (97% de vraies prédictions).L'utilisation d'un mélange de lois de Student généralisées nous a permis de i) détecter et d'écarter un rat atypique et ii) construire des signatures pour chaque ROI avec un fort pouvoir discriminant pour les quatre modèles de tumeurs.

Published
2015

3. In situ nanochemical imaging of label-free drugs: a case study of antimalarials in Plasmodium falciparum-infected erythrocytes

Author

Christophe Biot, P.A. Thomas, Yann Guérardel, Jean-Charles Morin, Jamal Khalife, Christian Slomianny, Sylvain Bohic, Hadidjatou Kalamou, Peter Cloetens, Faustine Dubar, Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), 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), IPL Santé Environnement Durable, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), European Synchrotron Radiation Facility (ESRF), Schistosomiase, paludisme et inflammation, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, 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’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)

Subjects
Erythrocytes, Metallocenes, Plasmodium falciparum, Pharmacology, 010402 general chemistry, 01 natural sciences, Mass Spectrometry, Catalysis, Antimalarials, Microscopy, Electron, Transmission, Materials Chemistry, High spatial resolution, Ferrous Compounds, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Label free, biology, 010405 organic chemistry, Chemistry, Metals and Alloys, Spectrometry, X-Ray Emission, Biological Transport, General Chemistry, biology.organism_classification, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0104 chemical sciences, 3. Good health, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Aminoquinolines, Ceramics and Composites
Abstract

International audience; We report here for the first time the in vitro localization of unlabeled antimalarial drugs with high spatial resolution. This strategy further enhances our understanding of the action mechanisms of antimalarial drugs. Our approach may be applied to a wide range of domains where quantitative chemical imaging of drugs at the sub-cellular level appears critical.

Published
2012
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4. Comparison of manual versus automatic delineation of low-grade gliomas based on MR brain scans

Author

Doyle, Senan, Lemasson, Benjamin, Vasseur, Flor, Bourdillion, Pierre, Ducray, François, Honnorat, Jérôme, Guilloton, Laurent, Guyotat, Jacques, Remy, Chantal, Forbes, Florence, Cotton, François, Barbier, Emmanuel, Dojat, Michel, Modelling and Inference of Complex and Structured Stochastic Systems (MISTIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Jean Kuntzmann (LJK), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), 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), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Association des Neuro-Oncologues d'Expression Française (ANOCEF), Hôpital de la Timone [CHU - APHM] (TIMONE)-CHU Marseille, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Hôpital d'Instruction des Armées Desgenettes, Service de Santé des Armées, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (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)-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), INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, European Synchrotron Radiation Facility (ESRF)-Grenoble Institut des Neurosciences (GIN), Neuroimagerie fonctionnelle et perfusion cérébrale, 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), Institut National des Sciences Appliquées (INSA)-Université de Lyon-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), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-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)

Subjects
[MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

5. 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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6. 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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7. 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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8. 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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9. 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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10. Thlaspi arvense binds Cu(II) as a bis-(L-histidinato) complex on root cell walls in an urban ecosystem

Author

Kathryn L. Nagy, Jean-Philippe Bedell, Alexandre Simionovici, Alain Manceau, Martine Lanson, Jonathan Perrin, Rémi Tucoulou, Sylvain Bohic, Matthew A. Marcus, Sirine C. Fakra, Minéralogie et environnements, Institut des Sciences de la Terre (ISTerre), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF), European Synchrotron Radiation Facility (ESRF), ANTE-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)-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), Advanced Light Source [LBNL Berkeley] (ALS), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Impacts des Polluants sur les Écosystèmes, Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), 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-École Nationale des Travaux Publics de l'État (ENTPE)-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-École Nationale des Travaux Publics de l'État (ENTPE), Department of Earth and Environmental Sciences [Chicago] (EAES), University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Université Joseph Fourier - Grenoble 1 (UJF)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-PRES Université de Grenoble-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-PRES Université de Grenoble-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-PRES Université de Grenoble-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), 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), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, 0106 biological sciences, Denticity, Biophysics, chemistry.chemical_element, Plant Roots, 01 natural sciences, Biochemistry, Biomaterials, Metal, 03 medical and health sciences, chemistry.chemical_compound, subcellular-localization, Cell Wall, Coordination Complexes, ray-absorption spectroscopy, medicine, Imidazole, Histidine, Chelation, elsholtzia-splendens, Ecosystem, Thlaspi arvense, 030304 developmental biology, 0303 health sciences, biology, Lability, Copper toxicity, Metals and Alloys, medicine.disease, biology.organism_classification, Copper, Thlaspi, Crystallography, chemistry, in-situ, Chemistry (miscellaneous), visual_art, Environmental chemistry, visual_art.visual_art_medium, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, 010606 plant biology & botany
Abstract

International audience; Root cell walls accumulate metal cations both during acquisition from the environment and removal from the protoplast to avoid toxicity, but molecular forms of the metals under field conditions remain elusive. We have identified how copper is bound to cell walls of intact roots of native Thlaspi arvense by combining synchrotron X-ray fluorescence and absorption techniques (XANES and EXAFS) at the nano-, micro-, and bulk scales. The plants grew naturally in sediment in a stormwater runoff basin at copper concentrations typical of urban ecosystems. About 90% of acquired copper is bound in vivo to cell walls as a unique five-coordinate Cu(II)-bis(L-histidinato) complex with one L-histidine behaving as a tridentate ligand (histamine-like chelate) and the other as a bidentate ligand (glycine-like chelate). Tridentate binding of Cu(II) would provide thermodynamic stability to protect cells against copper toxicity, and bidentate binding may enable kinetic lability along the cell wall through protein-protein docking with the non-bonded imidazole group of histidine residues. EXAFS spectra are provided as ESI dagger to facilitate further identification of Cu-histidine and distinction of Cu-N from Cu-O bonds in biomolecules.

Published
2013
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11. 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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12. Deciphering the resistance-counteracting functions of the antimalarial ferroquine in Plasmodium falciparum-infected erythrocytes

Author

Dubar, Faustine, Bohic, Sylvain, Dive, Daniel, Guérardel, Yann, Cloetens, Peter, Khalife, Jamal, Biot, Christophe, Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), Centrale Lille Institut (CLIL)-Université d'Artois (UA)-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Lille, 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’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Ministère de l'enseignement supérieur, We are grateful to Hadidjatou Kalamou for technical support. We acknowledge the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities., Serduc, Raphael, Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), 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), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, chloroquine, drug resistance, drug delivery, ferroquine, antiparasitic agents, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences
Abstract

International audience; he aminoquinoline chloroquine (CO) has been widely used for treating malaria since World War II. Resistance to CQ began to spread around 1957 and is now found in all malarious areas of the world. CQ resistance is caused by multiple mutations in the Plasmodium falciparum chloroquine resistance transporter (PfCRT). These mutations result in an increased efflux of CQ from the acidic digestive vacuole (DV) to the cytosol of the parasite. This year, we proposed a strategy to locate and quantify the aminoquinolines in situ within infected red blood cells (iRBCs) using synchrotron based X-ray nanoprobe fluorescence. Direct measurements of unlabeled CQ and ferroquine (FQ) (a ferrocene-CQ conjugate, extremely active against CQ-resistant strains) enabled us to evidence fundamentally different transport mechanisms from the cytosol to the DV between CQ and FQ in the CQ:susceptible strain HB3. These results inspired the present study of the localization of CQ and FQ in the CQ:resistant strain W2. The introduction of the ferrocene core in the lateral side chain of CQ has an important consequence: the transporter is unable to efflux FQ from the DV. We also found that resistant parasites treated by FQ accumulate a sulfur-containing compound, credibly glutathion, in their DV.

Published
2012
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13. 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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14. The over-expression of TRPC6 channels in HEK-293 cells favours the intracellular accumulation of zinc

Author

Sylvain Bohic, Pierre Richaud, Michael X. Zhu, Alexandre Bouron, Julien Gibon, Guylain Boulay, Peng Tu, Josiane Arnaud, Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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), 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), Laboratoire des Echanges Membranaires et Signalisation (LEMS), Université de la Méditerranée - Aix-Marseille 2-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Molecular Biology, Ohio State University [Columbus] (OSU), Department of Pharmacology, University of Sherbrook, CNRS (programme Longévité Viellissement) and Rhône-Alpes Région (Cluster 11), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Serduc, Raphael

Subjects
inorganic chemicals, Biophysics, chemistry.chemical_element, TRPC6, Zinc, AMPA receptor, Biochemistry, MESH: Zinc, Cell Line, 03 medical and health sciences, 0302 clinical medicine, TRPC3, MESH: Colorimetry, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, TRPC6 Cation Channel, Homeostasis, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: TRPC Cation Channels, 030304 developmental biology, Diacylglycerol kinase, Fluorescent Dyes, TRPC Cation Channels, 0303 health sciences, MESH: Humans, HEK 293 cells, Brain, Cell Biology, MESH: Fluorescent Dyes, MESH: Cell Line, Electrophysiology, chemistry, Oxidative stress, MESH: Homeostasis, TRPC channel, Colorimetry, 030217 neurology & neurosurgery, Intracellular
Abstract

International audience; TRPC6 are plasma membrane cation channels. By means of live-cell imaging and spectroscopic methods, we found that HEK cells expressing TRPC6 channels (HEK-TRPC6) are enriched in zinc and sulphur and have a reduced copper content when compared to HEK cells and HEK cells expressing TRPC3 channels (HEK-TRPC3). Hence, HEK-TRPC6 cells have larger pools of mobilizable Zn2+ and are more sensitive to an oxidative stress. Synchrotron X-ray fluorescence experiments showed a higher zinc content in the nuclear region indicating that the intracellular distribution of this metal was influenced by the over-expression of TRPC6 channels. Their properties were investigated with the diacylglycerol analogue SAG and the plant extract hyperforin. Electrophysiological recordings and imaging experiments with the fluorescent Zn2+ probe FluoZin-3 demonstrated that TRPC6 channels form Zn2+-conducting channels. In cortical neurons, hyperforin-sensitive channels co-exist with voltage-gated channels, AMPA and NMDA receptors, which are known to transport Zn2+. The ability of these channels to regulate the size of the mobilizable pools of Zn2+ was compared. The data collected indicate that the entry of Zn2+ through TRPC6 channels can up-regulate the size of the DTDP-sensitive pool of Zn2+. By showing that TRPC6 channels constitute a Zn2+ entry pathway, our study suggests that they could play a role in zinc homeostasis.

Published
2011
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15. Role of EG-VEGF in human placentation: Physiological and pathological implications

Author

Jean-Jacques Feige, Jean-Patrick Schaal, Yasmina Saoudi, Mohamed Benharouga, Charles H. Graham, Chafika Mazouni, Nadia Alfaidy, Pascale Hoffmann, Service gynécologie, obstétrique et médecine de reproduction, CHU Grenoble, Angiogenèse hormono-regulée et angiogenèse tumorale (LAPV), 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), INSERM U836, équipe 1, Physiopathologie du cytosquelette, 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), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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), Department of Anatomy and Cell Biology, Queen's University, Service de Gynécologie et Obstétrique [Marseille], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), INSERM U878 CEA Programme National de Recherche en Reproduction et Endocrinologie, Département de Gynécologie, Obstétrique et Médecine de la Reproduction, 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Gynécologie Obstétrique, Hôpital Nord [CHU - APHM], Andrieux, Annie, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA)

Subjects
Adult, medicine.medical_specialty, pre-eclampsia, Placenta, medicine.medical_treatment, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Biology, 03 medical and health sciences, Paracrine signalling, chemistry.chemical_compound, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, trophoblast invasion, Internal medicine, medicine, Humans, EG-VEGF, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, 030304 developmental biology, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Humans, Molecular Target, Growth factor, Decidua, Trophoblast, Placentation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Adult, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, medicine.disease, MESH: Placenta, Vascular endothelial growth factor, prokineticin, medicine.anatomical_structure, Endocrinology, chemistry, MESH: Vascular Endothelial Growth Factor, Endocrine-Gland-Derived, Molecular Medicine, Female, Vascular Endothelial Growth Factor, Endocrine-Gland-Derived, MESH: Female
Abstract

International audience; Pre-eclampsia (PE), the major cause of maternal morbidity and mortality, is thought to be caused by shallow invasion of the maternal decidua by extravillous trophoblasts (EVT). Data suggest that a fine balance between the expressions of pro- and anti-invasive factors might regulate EVT invasiveness. Recently, we showed that the expression of the new growth factor endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is high in early pregnancy but falls after 11 weeks, suggesting an essential role for this factor in early pregnancy. Using human villous explants and HTR-8/SVneo, a first trimester extravillous trophoblast cell line, we showed differential expression of EG-VEGF receptors, PKR1 and PKR2, in the placenta and demonstrated that EG-VEGF inhibits EVT migration, invasion and tube-like organisation. EG-VEGF inhibitory effect on invasion was supported by a decrease in matrix metalloproteinase (MMP)-2 and MMP-9 production. Interference with PKR2 expression, using specific siRNAs, reversed the EG-VEGF-induced inhibitory effects. Furthermore, we determined EG-VEGF circulating levels in normal and PE patients. Our results showed that EG-VEGF levels were highest during the first trimester of pregnancy and decreased thereafter to non-pregnant levels. More important, EG-VEGF levels were significantly elevated in PE patients compared with age-matched controls. These findings identify EG-VEGF as a novel paracrine regulator of trophoblast invasion. We speculate that a failure to correctly down-regulate placental expression of EG-VEGF at the end of the first trimester of pregnancy might lead to PE.

Published
2009
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16. 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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17. 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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18. Combined use of hard X-ray phase contrast imaging and X-ray fluorescence microscopy for sub-cellular metal quantification

Author

Heikki Suhonen, Ewelina Kosior, Sylvain Bohic, Asuncion Carmona, Jean Francois Guillet, Florence Marchi, Peter Cloetens, Richard Ortega, Guillaume Devès, Serduc, Raphael, European Synchrotron Radiation Facility (ESRF), 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), CP, Physics department - UFR PHITEM, Université Joseph Fourier - Grenoble 1 (UJF)-Université Joseph Fourier - Grenoble 1 (UJF)-Surface Science Laboratory, European Synchrotron Radiation Facility (ESRF)-European Synchrotron Radiation Facility (ESRF), Surface Science Laboratory, and 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)

Subjects
Analytical chemistry, X-ray fluorescence, Synchrotron radiation, MESH: Microscopy, Fluorescence, 02 engineering and technology, 01 natural sciences, MESH: Zinc, PC12 Cells, law.invention, Structural Biology, law, Microscopy, Fluorescence microscope, MESH: Animals, Microscopy, Phase-Contrast, MESH: Microscopy, Phase-Contrast, Chemistry, Phase-contrast imaging, Reference Standards, 021001 nanoscience & nanotechnology, Synchrotron, Zinc, X-Ray Phase-Contrast Imaging, Calibration, MESH: Reference Standards, Single-Cell Analysis, 0210 nano-technology, Algorithms, MESH: Cell Nucleus, MESH: Rats, MESH: Algorithms, MESH: Trace Elements, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, MESH: Calibration, MESH: X-Rays, Optics, synchrotron, MESH: PC12 Cells, Animals, MESH: Particle Size, Particle Size, Cell Nucleus, business.industry, X-Rays, 010401 analytical chemistry, 0104 chemical sciences, Rats, Trace Elements, Microscopy, Fluorescence, Light sheet fluorescence microscopy, MESH: Potassium, Potassium, business, phase contrast imaging, MESH: Single-Cell Analysis
Abstract

International audience; Hard X-ray fluorescence microscopy and magnified phase contrast imaging are combined to obtain quantitative maps of the projected metal concentration in whole cells. The experiments were performed on freeze dried cells at the nano-imaging station ID22NI of the European Synchrotron Radiation Facility (ESRF). X-ray fluorescence analysis gives the areal mass of most major, minor and trace elements; it is validated using a biological standard of known composition. Quantitative phase contrast imaging provides maps of the projected mass and is validated using calibration samples and through comparison with Atomic Force Microscopy and Scanning Transmission Ion Microscopy. Up to now, absolute quantification at the sub-cellular level was impossible using X-ray fluorescence microscopy but can be reached with the use of the proposed approach.

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