Neutrophils do not contribute to infarction, oxidative stress, and NO synthase activity in severe brain ischemia.
Polymorphonuclear leukocytes (PMNs) were reported to contribute to ischemia-reperfusion-induced brain damage. The present work examined whether PMN infiltration is deleterious in a severe model of transient focal cerebral ischemia and in which part PMNs contribute to oxidative stress and nitric oxide (NO) production. A 20-min occlusion of the left middle cerebral artery and both common carotid arteries was performed in rats. Infarction was maximal 24 h after reperfusion, while accumulation of PMNs in infarcted tissue was not significant before 48 h. Moreover, neutropenia induced by vinblastine (0.5 mg/kg iv) significantly decreased by 60-80% PMN infiltration 48 h after reperfusion but did not reduce the infarct volume. Thus PMNs do not contribute to cerebral injury in our model. Furthermore, decreased PMN infiltration modified neither oxidative stress evaluated by glutathione concentrations nor NO synthase activities 48 h after reperfusion. In conclusion, our results suggest that PMNs are not involved in severe cerebral ischemia and that anti-PMN strategies may be inefficient in some pathological conditions.
Beray-Berthat
Virginie
V
Laboratoire de Pharmacologie, UPRES EA2510, Université René Descartes, F-75006, Paris, France.
Palmier
Bruno
B
Plotkine
Michel
M
Margaill
Isabelle
I
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005978:Glutathione / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014747:Vinblastine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D009569:Nitric Oxide; D014747:Vinblastine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D002118:Calcium