Microglia provide neuroprotection after ischemia

Abstract

ABSTRACT Many neurological insults are accompanied by a marked acute inflammatory reaction, involving the activation of microglia. Using a model of exogenous application of fluorescence‐labeled BV2 microglia in pathophysiologically relevant concentrations onto organotypic hippocampal slice cultures, we investigated the specific effects of microglia on neuronal damage after ischemic injury. Neuronal cell death after oxygen‐glucose deprivation (OGD) was determined by propidium iodide incorporation and Nissl staining. Migration and interaction with neurons were analyzed by time resolved 3‐D two‐photon microscopy. We show that microglia protect against OGD‐induced neuronal damage and engage in close physical cell‐cell contact with neurons in the damaged brain area. Neuroprotection and migration of microglia were not seen with integrin regulator CD11a‐deficient microglia or HL‐60 granulocytes. The induction of migration and neuron‐microglia interaction deep inside the slice was markedly increased under OGD conditions. Lipopolysaccharide‐prestimulated microglia failed to provide neuroprotection after OGD. Pharmacological interference with microglia function resulted in a reduced neuroprotection. Microglia proved to be neuroprotective even when applied up to 4 h after OGD, thus defining a “protective time window.” In acute injury such as trauma or stroke, appropriately activated microglia may primarily have a neuroprotective role. Anti‐inflammatory treatment within the protective time window of microglia would therefore be counterintuitive.

Keywords

Affiliated Institutions

• University Hospital Magdeburg DE
• Helmholtz Centre for Infection Research DE
• Technische Universität Dresden DE
• Leibniz Institute for Neurobiology DE

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