Phagocytic response in photochemically induced infarction of rat cerebral cortex. The role of resident microglia

Abstract

Background and purpose: In this study we assessed the relative extent to which resident microglia and blood-borne macrophages contribute to the population of phagocytes after focal infarction of the rat cortex.

Methods: Focal cerebral infarction was induced in rats by photothrombosis after hematogenous macrophages were depleted by means of liposomes containing dichloromethylene diphosphonate. The phagocytic activation of microglia and macrophages was monitored by immunocytochemistry with the antibody ED1.

Results: In both macrophage-depleted rats and controls, ED1+ phagocytes bordered the infarct to the same extent at day 3 after photothrombosis. By contrast, at day 6 after photothrombosis ED1+ phagocytes in control rats greatly outnumbered those in macrophage-depleted rats. With the use of the antibody Ox42 directed against the CR3 receptor on the surface of microglia, it was possible to selectively document the transition of resident microglia into stellate and ameboid phagocytic microglia during the first 6 days after photothrombosis in the absence of bloodborne macrophages.

Conclusions: The initial phagocytic response after focal brain ischemia is an intrinsic property of the nervous system mainly performed by resident microglia. The majority of hematogenous macrophages are recruited secondarily to participate in the removal of necrotic tissue.