title: Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat.
abstract: Free radicals have been suggested to be largely involved in the genesis of ischemic brain damage, as shown in the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, against ischemic cerebral injury. In the present study, the effects of PBN as well as MCI-186, a newly-developed free radical scavenger, and oxypurinol, an inhibitor of xanthine oxidase, were evaluated in a rat transient middle cerebral aretery (MCA) occlusion model to clarify the possible role of free radicals in the reperfusion injury of brain. The volume of cerebral infarction, induced by 2-h occlusion and subsequent 2-h reperfusion of MCA in Fisher-344 rats, was evaluated. The administration of PBN (100 mg/kg) and MCI-186 (100 mg/kg) just before reperfusion of MCA significantly reduced the infarction volume. In contrast, oxypurinol (100 mg/kg) failed to show any preventive effect on the infarction. These results suggest that free radical formation is involved in the cerebral damage induced by ischemia-reperfusion of MCA, and that hydroxyl radical is responsible for the reperfusion injury after transient focal brain ischemia. It is also suggested that xanthine oxidase is not a major source of free radicals.
authors.affiliation: Department of Pharmacology, Gifu University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Niwa
authors.forename: T
authors.initials: T
authors.lastname: Iwai
authors.forename: T
authors.initials: T
authors.lastname: Uematsu
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019335:Nitroarginine / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D013113:Spin Labels; D013477:Superior Colliculi / Q000187:drug effects / Q000473:pathology
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D009589:Nitrogen Oxides; D013113:Spin Labels; D019335:Nitroarginine; C029217:phenyl-N-tert-butylnitrone; D000077553:Edaravone; D000983:Antipyrine