Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats.
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.
Tsai
Shen-Kou
SK
Department of Anesthesiology, College of Medicine, Buddhist Tzu-Chi University and Hospital, Taipei, Taiwan.
Hung
Li-Man
LM
Fu
Yuan-Tsung
YT
Cheng
Henrich
H
Nien
Mao-Wei
MW
Liu
Hsin-Yi
HY
Zhang
Friedrich Bo-Yuan
FB
Huang
Shiang-Suo
SS
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
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