Melatonin ameliorates cerebral vasospasm after experimental subarachnoidal haemorrhage correcting imbalance of nitric oxide levels in rats.
In the present study, we investigated the in vivo effects of melatonin on SAH-induced cerebral vasospasm and oxidative stress, resulting from SAH in an experimental rat model. Twenty-eight rats (225-250 g) were divided into four groups equally: group 1; control, group 2; SAH, group 3; SAH plus placebo, and group 4; SAH plus melatonin. We used double haemorrhage method for SAH groups. Beginning 6 h after SAH, 20 mg/kg melatonin or equal volume of 0.9% saline was administered intraperitoneally twice daily for 5 days to groups 3 and 4, respectively. Melatonin or 0.9% saline injections were continued up to fifth day after SAH and rats were sacrificed at the end of this period. Brain sections at the level of the pons were examined by light microscopy. The lumen diameter and the vessel wall thickness of basilar artery were measured using a micrometer. The serum levels of cerebral vasodilator nitric oxide (NO), the brain levels of an intrinsic antioxidant superoxide dismutase (SOD) and a NO regulator arginase activities were measured. The brain levels of inducible nitric oxide (iNOS) and nitrotyrosine, a nitrosative stress parameter immunohistochemiacally determined. In conclusion, melatonin administration ameliorated cerebral vasospasm by increasing serum NO level and decreasing the brain the levels of arginase and oxidative stress. It is therefore possible that increased brain arginase activity after SAH may also have a significant role in the pathogenesis of vasospasm by limiting the availability of arginine for NO production.
Aladag
M A
MA
Department of Neurosurgery, Inonu University School of Medicine, Malatya, Turkey. marifaladag@hotmail.com
Turkoz
Y
Y
Parlakpinar
H
H
Ozen
H
H
Egri
M
M
Unal
S C
SC
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001119:Arginase / Q000502:physiology; D001488:Basilar Artery / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D003251:Constriction, Pathologic / Q000209:etiology / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D000975:Antioxidants; D005609:Free Radicals; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D001119:Arginase; D008550:Melatonin