Modulation by nitric oxide of cerebral neutrophil accumulation after transient focal ischemia in rats

beneficial role of nitric oxide (NO) after cerebral ischemia has been previ ously attributed to its vascular effects. Recent data indicate a regulatory role for NO in initial leukocyte-endothelial interactions in the cerebral microcirculation under basal and ischemic conditions. In this study, the au thors tested the hypothesis that endogenous NO production during and/or aft er transient focal cerebral ischemia can also be neuroprotective by limitin g the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left mi ddle cerebral artery and the left common carotid artery. The effect of N-G- nitro-L-arginine methyl ester (r-NAME) (10 mg/kg, intra-peritaneally), an N O synthase inhibitor, was examined at 48 hours after ischemia on both infar ct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical i nfarct volume by 34% and increased cortical myeloperoxidase activity by 60% , whereas administration of L-NAME at 1, 7, and 22 hours of reperfusion had no effect. Such exacerbations of infarction and myeloperoxidase activity p roduced when L-NAME was given 5 minutes after the onset of ischemia were no t observed in rats rendered neutropenic by vinblastine These results sugges t that after transient focal ischemia, early NO production exerts a neuropr otective effect by modulating neutrophil infiltration.