Protective effects of melatonin in ischemic brain injury

Recent studies have demonstrated that melatonin is a scavenger of oxyradica ls and peroxynitrite and an inhibitor of nitric oxide (NO) production. NO, peroxynitrite (formed from NO and superoxide anion), and poly (ADP-Ribose) synthetase (PARS) have been implicated as mediators of neuronal damage foll owing focal ischemia. In the present study, we have investigated the effect s of melatonin treatment in Mongolian gerbils subjected to cerebral ischemi a. Treatment of gerbils with melatonin (10 mg kg(-1), 30 min before reperfu sion and 1, 2, and 6 hr after reperfusion) reduced the formation of post-is chemic brain edema, evaluated by water content. Melatonin also attenuated t he increase in the brain levels malondialdehyde (MDA) and the increase in t he hippocampus of myeloperoxidase (MPO) caused by cerebral ischemia. Positi ve staining for nitrotyrosine was found in the hippocampus of Mongolian ger bils subjected to cerebral ischemia. Hippocampus tissue sections, from Mong olian gerbils subjected to cerebral ischemia, also showed positive staining for PARS. The degrees of staining for nitrotyrosine and for PARS were mark edly reduced in tissue sections obtained from animals that received melaton in. Melatonin treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histolo gical observations of the pyramidal layer of CA-1 showed a reduction of neu ronal loss in animals that received melatonin. These results show that mela tonin improves brain injury induced by transient cerebral ischemia.