Protective effect of melatonin in a model of traumatic brain injury in mice.
The pineal hormone melatonin has recently been shown to exert neuroprotective activity in a variety of experimental neuropathologies in which free radicals are involved. This neuroprotective effect has been attributed to the antioxidant properties of melatonin. Considering that free radicals also play a deleterious role in traumatic brain injury (TBI), the purpose of the present study was to determine whether melatonin would have a beneficial effect in this pathology. Head injury was induced in mice and the neurological deficit was evaluated at 24 hr by a grip test. In this model, the free radical scavenger, alpha-phenyl-tert-butyl-nitrone (2 x 100 mg/kg, i.p.) given 5 min and repeated at 4 hr after TBI was neuroprotective. Melatonin (1.25 mg/kg, i.p.) given 5 min and repeated at 1, 2, and 3 hr after head trauma also significantly reduced the neurological deficit. This beneficial effect was not due to melatonin-induced hypothermia since repeated treatment with melatonin did not modify the colonic temperature of mice. This study shows that melatonin exerts a beneficial effect on the neurological deficit induced by traumatic brain injury in mice. The mechanisms of this neuroprotection remains to be established, and more particularly, the contribution of the antioxidant activity of melatonin.
Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001831:Body Temperature; D001930:Brain Injuries / Q000517:prevention & control*; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009589:Nitrogen Oxides / Q000494:pharmacology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D008550:Melatonin