title: Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats.
abstract: BACKGROUND
  Our prior study showed that resveratrol could suppress infarct volume and exert neuroprotective effect on rats subjected to focal cerebral ischemia (FCI) injury. Recently, it has been reported in some literature that resveratrol protects the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Therefore, this study was designed to investigate the role of nitric oxide on the neuroprotective mechanisms of resveratrol on rats after FCI injury.
  
  
  METHODS
  The FCI injury was induced by the middle cerebral artery (MCA) occlusion for 1 hour and then a 24-hour reperfusion followed in the anesthetized Long-Evans rats. Resveratrol was intravenously injected after 1 hour MCA occlusion.
  
  
  RESULTS
  Treatment of resveratrol (0.1 and 1 microg/kg) decreased the lactate dehydrogenase (LDH) in plasma and malondialdehyde (MDA) in FCI injury brain tissue, whereas the level of NO in plasma was increased. In addition, resveratrol downregulated protein and mRNA expression of inducible nitric oxide synthase (iNOS), and upregulated protein and mRNA expression of endothelial nitric oxide synthase (eNOS), while the expression of protein and mRNA of neuronal nitric oxide synthase (nNOS) was unchanged. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, the nonselective NOS inhibitor) or L-N(5)-(1-iminoethyl)-ornithine (L-NIO, the eNOS selective inhibitor) completely blocked the effect of resveratrol in decreasing infarction volumes.
  
  
  CONCLUSIONS
  This study demonstrated the important role of NO in the neuroprotective effect of resveratrol in FCI injury.
authors.affiliation: Department of Anesthesiology, College of Medicine, Buddhist Tzu-Chi University and Hospital, Taipei, Taiwan.
authors.forename: Shen-Kou
authors.initials: SK
authors.lastname: Tsai
authors.forename: Li-Man
authors.initials: LM
authors.lastname: Hung
authors.forename: Yuan-Tsung
authors.initials: YT
authors.lastname: Fu
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
authors.forename: Mao-Wei
authors.initials: MW
authors.lastname: Nien
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Liu
authors.forename: Friedrich Bo-Yuan
authors.initials: FB
authors.lastname: Zhang
authors.forename: Shiang-Suo
authors.initials: SS
authors.lastname: Huang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008026:Ligation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020768:Middle Cerebral Artery / Q000601:surgery; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D013267:Stilbenes; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D008315:Malondialdehyde; D009952:Ornithine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D000077185:Resveratrol; D019331:NG-Nitroarginine Methyl Ester