Protective effects of melatonin in ischemic brain injury

Salvatore Cuzzocrea, Giuseppina Costantino, Eloisa Gitto, Emanuela Mazzon, Francesco Fulia, Ivana Serraino, Santina Cordaro, Ignazio Barberi, Angela De Sarro, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)217-227
Number of pages11
JournalJournal of Pineal Research
Issue number4
Publication statusPublished - 2000


  • Brain edema
  • Brain injury
  • Cerebral ischemia
  • Gerbil
  • Lipid peroxidation
  • Melatonin
  • Neuronal death

ASJC Scopus subject areas

  • Endocrinology


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