Abstract
Background and purpose:
CD200 (cluster of differentiation 200), a highly glycosylated protein primarily expressed on neurons in the central nervous system, binds with its receptor CD200R to form an endogenous inhibitory signal against immune responses. However, little is known about the effect of neuronal CD200 signaling in cerebral ischemia. The aim of this study was to investigate how neuronal CD200 signaling impacts poststroke inflammation and the ischemic injury.
Methods:
CD200 tma1lf/fl:Thy1CreER mice were treated with tamoxifen to induce conditional gene knockout (ICKO) of neuronal CD200. The mice were subjected to a 60-minute transient middle cerebral artery occlusion. Stroke outcomes, apoptotic cell death, immune cell infiltration, microglia activation, and other inflammatory profiles were evaluated at 3 and 7 days after stroke.
Results:
Infarct volumes were significantly larger, and behavioral deficits more severe in ICKO versus control mice at 3 days after middle cerebral artery occlusion. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay also revealed a significant increase in apoptotic neuronal death in CD200 ICKO mice. An enhancement in lymphocytic infiltration and microglial proinflammatory responses were revealed by flow cytometry at 3 and 7 days after stroke in ICKO mice, accompanied by an increased microglial phagocytosis activity. Plasma proinflammatory cytokine (TNFα [tumor necrosis factor alpha] and IL [interleukin]-1β) levels significantly increased at 3 days, and IL-1β/IL-6 levels increased at 7 days in ICKO versus control animals. ICKO led to significantly lower baseline level of CD200 both in brain and plasma.
Conclusions:
Neuronal CD200 inhibits proinflammatory responses and is protective against stroke injury.