© 2014, Springer Science+Business Media New York.In our study, we investigated transient global cerebral ischemia (TGCI)-induced changes in spatial memory and motor activity together with apoptotic, oxidant, and NO/NOS signaling parameters in rats and the effects of treatment of animals with ghrelin. The TGCI-induced deficiencies of spatial memory and motor activity in the Y-maze and open field tests were attenuated by ghrelin treatment. Furthermore, ghrelin administration lowered the levels of caspase-3 and iNOS elevated by TGCI in the hippocampus. Thus, we conclude that ghrelin exerts a neuroprotective action against hippocampal TGCI injury via influencing apoptotic, oxidant, and/or NO/NOS pathways. If the underlying mechanisms of action of this agent are fully clarified, ghrelin might be a candidate drug for treatment of TGCI-induced memory impairments.