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Protective effects of melatonin in ischemic brain injury
Author(s) -
Cuzzocrea Salvatore,
Costantino Giuseppina,
Gitto Eloisa,
Mazzon Emanuela,
Fulia Francesco,
Serraino Ivana,
Cordaro Santina,
Barberi Ignazio,
De Sarro Angela,
Caputi Achille P.
Publication year - 2000
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-0633.2002.290404.x
Subject(s) - melatonin , peroxynitrite , ischemia , nitrotyrosine , gerbil , nitric oxide , endocrinology , hippocampus , medicine , free radical scavenger , cerebral edema , nitric oxide synthase , anesthesia , oxidative stress , chemistry , superoxide , biochemistry , enzyme
Recent studies have demonstrated that melatonin is a scavenger of oxyradicals 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 following focal ischemia. In the present study, we have investigated the effects of melatonin treatment in Mongolian gerbils subjected to cerebral ischemia. Treatment of gerbils with melatonin (10 mg kg−1, 30 min before reperfusion and 1, 2, and 6 hr after reperfusion) reduced the formation of post‐ischemic brain edema, evaluated by water content. Melatonin also attenuated the increase in the brain levels malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischemia. Positive staining for nitrotyrosine was found in the hippocampus of Mongolian gerbils subjected to cerebral ischemia. Hippocampus tissue sections, from Mongolian gerbils subjected to cerebral ischemia, also showed positive staining for PARS. The degrees of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received melatonin. Melatonin treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CA‐1 showed a reduction of neuronal loss in animals that received melatonin. These results show that melatonin improves brain injury induced by transient cerebral ischemia.