The vascular endothelium becomes pro-thrombotic and pro-inflammatory after ischemia/reperfusion, eliciting microcirculatory disturbance and post-ischemic inflammation. First, with mouse model of ischemia/reperfusion, we compared efficacy of cilostazol (n=6), aspirin (n=6) and vehicle (n=6) administered before and after ischemia. Thrombus formation in the injured artery was suppressed in the cilostazol group and aspirin group compared with that in the control group, though all injured arteries were virtually occluded after 150 seconds. Spontaneous recanalization of the thrombosed artery was confirmed at 6 hours. Rolling leukocyte velocity over the microvessels at 24 hours was higher in the cilostazol group than in the aspirin group and control group. The number of adhering leukocytes was lower in the cilostazol group than in the control group, while aspirin did not suppress it significantly. We then confirmed protective effects of cilostazol on human brain microvascular endothelial cells (ECs) against pro-inflammatory changes
in vitro. These results suggest that cilostazol suppresses pro-inflammatory changes of ECs and reduces leukocyte rolling and adhesion onto the cerebral microvessels after reperfusion, contributing to its protective effects against reperfusion injury.
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