title: Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion.
abstract: Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood-brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique ("OxyBlot") was used to assess levels of protein carbonyl formation as a marker of oxidative stress-induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia-reperfusion is neuroprotective, and does not increase oxidative stress.
authors.affiliation: Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA. asinghal@partners.org
authors.forename: Aneesh B
authors.initials: AB
authors.lastname: Singhal
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Sumii
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mori
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D000818:Animals; D001158:Arteries; D001812:Blood-Brain Barrier; D002544:Cerebral Infarction / Q000473:pathology; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D018496:Hyperoxia; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D007700:Kinetics; D008297:Male; D020768:Middle Cerebral Artery / Q000601:surgery; D009419:Nerve Tissue Proteins / Q000737:chemistry; D018384:Oxidative Stress; D010100:Oxygen / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D011489:Protein Denaturation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
chemical_list: D009419:Nerve Tissue Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010100:Oxygen