Dual Role of Fcγ Receptor in Transient Focal Cerebral Ischemia in Mice

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Abstract
Background and Purpose— Cerebral ischemia/reperfusion injury is associated with the development of inflammatory response, including pathological contributions by vascular leukocytes and endogenous microglia. Expression of Fc receptors (FcRs) on macrophages and microglia is thought to be involved in the inflammatory cascade. The present study assessed the role of FcγR in ischemia/reperfusion injury, using FcγR knockout (FcγR −/− ) mice and bone marrow chimera FcγR −/− mice, which express enhanced green fluorescent protein (EGFP). Methods— Mice underwent occlusion of the middle cerebral artery for 60 minutes, followed by reperfusion. Infarct volume and mortality were calculated at several time points after ischemia. To clarify the function and distribution of microglia/macrophages, immunohistochemical staining and immunoblotting of ionized calcium-binding adapter molecule 1 (Iba-1), inducible nitric oxide synthase, and nitrotyrosine were performed. Results— FcγR −/− mice showed significantly reduced mortality (20%) and smaller infarcts (19.7±3.63 versus 33.28±7.98 mm 3 ; P P P −/− mice compared with WT mice. At 7 days after reperfusion, sections double-immunostained for EGFP and Iba-1 showed less activation and migration of EGFP-positive bone marrow–derived macrophages in FcγR −/− chimera mice than in WT mice. Conclusions— Our results demonstrated that the neuroprotective effect of FcγR deficiency in our model may be primarily attributed to the suppression of activation and infiltration of inflammatory cells.