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 FcR in ischemia/reperfusion injury, using FcR knockout (FcR^-/-) mice and bone marrow chimera FcR^-/- 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--FcR^-/- mice showed significantly reduced mortality (20%) and smaller infarcts (19.7±3.63 versus 33.28±7.98 mm³; P<0.001) than wild-type (WT) mice at 72 hours after reperfusion. Western blotting revealed that microglial activation (P<0.002) and induction of inducible nitric oxide synthase (P<0.005) were reduced in FcR^-/- 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 FcR^-/- chimera mice than in WT mice.

Conclusions--Our results demonstrated that the neuroprotective effect of FcR deficiency in our model may be primarily attributed to the suppression of activation and infiltration of inflammatory cells.