The effects of resveratrol on vasospasm after experimental subarachnoidal hemorrhage in rats.
BACKGROUND
Cerebral vasospasm remains a major cause of morbidity and mortality in patients with SAH. Although many pharmacologic agents and chemicals have been used to prevent and treat CV, the pathogenesis of that condition has not been established. We investigated the efficacy of resveratrol, a stilbene polyphenol and tyrosine kinase inhibitor that occurs naturally in grapes and red wine, in a murine basilar artery vasospasm model.


METHODS
Forty-two Wistar albino rats were used in this study. The rats were divided into 3 groups of 14 animals each: the sham-operated control group (group 1), the vasospasm group (group 2), and the treatment group (group 3). In groups 2 and 3, autologous blood (0.3 mL) was injected into the cisterna magna. After that injection, the rats in group 3 received an intravenous injection of resveratrol (10 mg/kg) for 72 hours. The evaluation of the response to both the injection of autologous blood and treatment was based on biochemical markers in tissue and serum and on light microscopic findings from the basilar artery, which were collected at different intervals after experimental SAH.


RESULTS
Endothelin-1 levels in brain tissue and serum were higher in the vasospasm group than in the control group (P < .05). In group 3 rats, the administration of resveratrol resulted in significantly lower ET-1 values than those in group 2. Brain and serum lipid peroxidation levels were markedly elevated in group 2 rats but decreased significantly after resveratrol treatment in group 3 rats (P < .05). Superoxide dismutase expression in brain tissue and serum was lower in group 2 rats than in sham-operated controls, and a significant increase in the SOD level was associated with resveratrol treatment. On examination via light microscopy 72 hours after SAH, the mean perimeters of the arterial lumen in groups 1, 2, and 3 were 719 +/- 16, 411.6 +/- 9, and 590.1 +/- 5.6 microm, respectively. The mean thickness of the arterial wall was as follows: in group 1, 11.1 +/- 0.8 microm; in group 2, 16.1 +/- 1.2 microm; and (after resveratrol treatment) in group 3, 13.4 +/- 0.6 microm.


CONCLUSIONS
The results of our study showed that resveratrol induced the relaxation of smooth muscle in the wall of the basilar artery and may be provided with neuroprotection against cerebral ischemia in a rat model. These effects may be associated with the antioxidant and vasodilatory effects of resveratrol, which could prove to be an agent prophylactic against CV and to be therapeutic for individuals who experience that event.
Karaoglan
Alper
A
Department of Neurosurgery, Taksim Education and Research Hospital, Istanbul, Turkey.
Akdemir
Osman
O
Barut
Seref
S
Kokturk
Sibel
S
Uzun
Hafize
H
Tasyurekli
Mustafa
M
Colak
Ahmet
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D019332:Endothelin-1 / Q000097:blood; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014715:Vertebrobasilar Insufficiency / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000975:Antioxidants; D019332:Endothelin-1; D013267:Stilbenes; D013482:Superoxide Dismutase; D000077185:Resveratrol