OBJECTIVES: This study was designed to examine whether melatonin has a neuroprotective effect against hippocampal neuronal damage following transient global ischemia in a gerbil. Polyamine is known to play a role in the pathophysiology of ischemic neuronal damage, we evaluated the influences of melatonin on the polyamine level as well as histology. MATERIAL AND METHODS: Male Mongolian gerbils (60-80 g) were used in this study. Transient global ischemia was induced by occlusion of the bilateral common carotid arteries for 3 min with microclips. Melatonin was administered immediately after occlusion. The animals were decapitated 24 h after the occlusion for polyamine measurement by a high performance liquid chromatography (HPLC) and 4 days after the occlusion for histological evaluation (hematoxylin and eosin staining). A histological examination was performed by a blinded investigator. RESULTS: The hippocampal putrescine level increased compared to sham-operated animals and the increase of putrescine was attenuated by 20 mg/kg melatonin administration. Spermidine and spermine levels didn't show significant changes after ischemia. Hippocampal neuronal damage in the CA1 region was markedly observed in vehicle-treated animals compared to sham-operated animals. Melatonin administration (10 or 20 mg/kg) significantly inhibited hippocampal CA1 neuronal damage after ischemia compared to corresponding vehicle-treated animals (p<0.05 and p<0.01, respectively). CONCLUSION: Melatonin attenuates the putrescine level after transient global ischemia and may have putative neuroprotective effects against global ischemia induced neuronal damage.