Background/Aims: To investigate the protective effect of SGK1 (serum- and glucocorticoidinducible protein kinase 1) in rat hippocampal neurons in vitro and in vivo following ischemia reperfusion (I/R). Methods: Isolated rat hippocampal neurons were subjected to 2 h of oxygen and glucose deprivation (OGD) then returned to normoxic conditions for 10, 30 or 60 min. Cell apoptosis and protein expression of SGK1 were analyzed. To examine SGK1 function, we overexpressed SGK1 in rat hippocampal neurons. Finally we examined the involvement of PI3K/Akt/GSK3 beta signaling by treating the cells (untransfected or transfected with expression vector encoding SGK1) with the PI3K inhibitor LY294002. Findings were confirmed in vivo in a rat model of middle cerebral artery occlusion. Resuits:I/R caused a time-dependent increase in apoptosis, both in vitro and in vivo. SGK1 protein levels decreased significantly under the same conditions. Overexpression of SGK1 reduced apoptosis following OGD or I/R compared to cells transfected with empty vector and subjected to the same treatment, or sham-operated animals. Addition of LY294002 revealed that the action of SGK1 in suppressing apoptosis was mediated by the PI3K/Akt/GSK3 beta pathway. Conclusion: SGK1 plays a protective role in ischemia reperfusion in rat hippocampal neurons, exerting its effects via the PI3K/Akt/GSK313 pathway. Copyright (C) 2014 S Karger AG, Basel