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Contenido archivado el 2024-06-18

Role of microglial phagocytosis in ischemic-hypoxic neuronal loss

Objetivo

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.

Ámbito científico (EuroSciVoc)

Programa(s)

Tema(s)

Convocatoria de propuestas

FP7-PEOPLE-2009-IEF
Consulte otros proyectos de esta convocatoria

Régimen de financiación

MC-IEF - Intra-European Fellowships (IEF)

Coordinador

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Aportación de la UE
€ 172 740,80
Dirección
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
Reino Unido
Región
East of England East Anglia Cambridgeshire CC
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
Sin datos