Objectif BACKGROUND: Inflammatory neurodegeneration occurs in most brain pathology, and may both protect and damage the brain. Inflammation in the brain is largely controlled by brain macrophages called microglia and when ischemia occurs microglia becomes activated in association with neuronal loss. AIMS: The aim of this project is to determine whether hypoxia-ischemia induces neuronal loss mediated by microglia and/or phagocytosis, and to test whether inhibition of phagocytosis blocks neuronal loss, leaving viable neurons. METHODS: We will use neurons co-cultured with astrocytes and/or microglia from neonatal rat or mouse brain. Co-cultures will be incubated in either excitotoxic or oxygen and glucose deprivation conditions of different durations to determine conditions in which maximal neuronal loss occurs without apparent cell death. Once we obtain such conditions, we will incubate cells with and without microglia to unravel whether this neuronal loss is induced by microglia and by or without contact with neurons (using transwells). Immunocytochemistry studies will determine neuron and microglia molecules involved in their interaction after hypoxia-ischemia. Video microscopy will be used to test whether neuronal loss is mediated by phagocytosis. Phagocytosis inhibition will be studied to determine whether it prevents neuronal loss. Neurons and/or microglia from MFG-E8 knockout mice and Mer kinase mutant rats will be used to further test the roles of phagocytosis and phagocytic signalling in ischemic neuronal loss. EXPECTED RESULTS: to unravel a new mode of neuronal death in hypoxia-ischemia conditions and to test for possible drug inhibitors to prevent such death. Champ scientifique natural sciencesbiological sciencesneurobiologynatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicinepathology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Appel à propositions FP7-PEOPLE-2009-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Contribution de l’UE € 172 740,80 Adresse TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Royaume-Uni Voir sur la carte Région East of England East Anglia Cambridgeshire CC Type d’activité Higher or Secondary Education Establishments Contact administratif Keith Cann (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
