Heterogeneity of the microglial response in photochemically induced focal ischemia of the rat cerebral cortex

This study examined microglial responses after photochemically induced foca l ischemia of the rat cortex. Microglial activation exceeded by far the are a of the ischemic lesion. Based on morphological criteria and expression of immunomolecules three distinct patterns could be distinguished. (1) In the infarct core and the border zone microglia transformed into phagocytes and removed debris with the aid of hematogeneous macrophages. Exclusively in t his area a subpopulation of CD8+ microglia/ macrophages was present. (2) In secondarily degenerating fibre tracts and nuclei with retrograde neuronal loss, microglia were activated with a delay of days and showed increased ex pression of complement receptor 3, major histocompatibility complex class I I and CD4 molecules, but only low phagocytic activity. (3) In remote ipsila teral cortex devoid of neuronal damage, microglia transiently responded by increased complement receptor 3, but not by major histocompatibility comple x class II and CD4 expression. Furthermore, the total number of microglia h ad increased. This remote response could partly be blocked by dizocilpine m aleate, a non-competitive N-methyl-D-aspartate receptor antagonist, implica ting a functional role of spreading depression. Taken together, our findings point to a tight and differential regulation o f microglial responses in the infarct core, degenerating fibre tracts and r emote brain regions without neuronal loss. (C) 1999 IBRO. Published by Else vier Science Ltd.