Modulation by nitric oxide of cerebral neutrophil accumulation after transient focal ischemia in rats.
A beneficial role of nitric oxide (NO) after cerebral ischemia has been previously 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 authors tested the hypothesis that endogenous NO production during and/or after transient focal cerebral ischemia can also be neuroprotective by limiting the process of neutrophil infiltration and its deleterious consequences. Male Sprague-Dawley rats were subjected to 2 hours occlusion of the left middle cerebral artery and the left common carotid artery. The effect of NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg, intraperitoneally), an NO synthase inhibitor, was examined at 48 hours after ischemia on both infarct size and myeloperoxidase activity, an index of neutrophil infiltration. L-NAME given 5 minutes after the onset of ischemia increased the cortical infarct 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 produced when L-NAME was given 5 minutes after the onset of ischemia were not observed in rats rendered neutropenic by vinblastine. These results suggest that after transient focal ischemia, early NO production exerts a neuroprotective effect by modulating neutrophil infiltration.
Batteur-Parmentier
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S
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
Margaill
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I
Plotkine
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D000818:Animals; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007958:Leukocyte Count; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009503:Neutropenia / Q000473:pathology; D009504:Neutrophils / Q000473:pathology*; D009569:Nitric Oxide / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester