Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice

Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5 min occlusion and 5 min reperfusion of unilateral renal artery) 24 h before global brain ischemia (20 min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5 mg/kg, i.p.) was injected 30 min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24 h after global ischemia. Apoptosis and neuronal cell density were assessed 72 h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC-FIR) suggesting a role for mTOR in RIPC induced hippocampal protection. (C) 2013 Elsevier B.V. All rights reserved.