The neuroprotection of leptin is mediated by leptin receptor. (a) Both the short and long isoforms of the leptin receptor (Ob-R) were expressed in rat hippocampal CA1 neurons. Sham: sham-operated group; 1 h and 4 h, one and four hours after global ischemia, respectively. (b) Leptin antagonist, LY294002 and PD98059 abolished the pro-survival role of leptin. Viable CA1 neurons were counted, and the mean numbers were plotted for each group. Sham: sham-operated; Veh.: vehicle-treated ischemia; Lep.: 6 μg leptin was injected into ICV at 20 min after global ischemia; Ant.: Leptin antagonist was injected into ICV 10 min before global ischemia; LY: LY294002 was injected into ICV 10 min before global ischemia; PD: PD98059 was injected into ICV 10 min before global ischemia. Data are mean ± SEM, assessed by anova and post hoc Scheffe's tests. **p < 0.01 vs. vehicle-treated ischemia group. #p < 0.05 vs. leptin-treated group and p > 0.05 vs. vehicle-treated ischemia group. (c) Leptin antagonist, LY294002 and PD98059 abolished the anti-apoptotic role of leptin. Dead (PANT positive) CA1 neurons were counted, and the mean number was plotted for each group. Sham: Sham-operated; Veh.: Vehicle-treated ischemia; Lep.: 6 μg leptin was injected into ICV at 20 min after global ischemia; Ant.: Leptin antagonist was injected into ICV 10 min before global ischemia; LY: LY294002 was injected into ICV 10 min before global ischemia; PD: PD98059 was injected into ICV 10 min before global ischemia. Data are mean ± SEM, assessed by anova and post hoc Scheffe's tests. **p < 0.01 vs. ischemia group. #p < 0.05 vs. leptin-treated group and p > 0.05 vs. vehicle-treated ischemia group.