Limb ischemic preconditioning attenuates neuronal apoptosis in CA1 hippocampus and brain edema evoked by brain ischemia via activating mitogen-activated protein kinase p38 in rats / 中国药理学与毒理学杂志

ABSTRACT

AIM To observe whether limb ischemic preconditioning (LIP) could attenuate pyramidal neuronal apoptosis of the CA1 hippocampus and brain edema evoked by brain ischemia in rats. METHODSSeventy-two rats whose bilateral vertebral arteries occluded permanently were randomly assigned into 6 groups: sham, LIP(bilateral femoral arteries were clamped for 10 min, 3 times, in a 10-min interval), brain ischemic insult, LIP+brain ischemic insult, DMSO+LIP+brain ischemic insult and SB 203580+LIP+brain ischemic insult groups. Assays for neuronal apoptosis were performed using TUNEL staining. The percentage of wet over dry tissue weight of the brain was measured by weighing method. RESULTS There were almost no TUNEL-positive cells in the CA1 hippocampus in either sham or LIP group. Clear TUNEL-positive pyramidal neurons of the CA1 hippocampus and increase in brain water content were detected in rats subjected to brain ischemic insult. But the number of TUNEL-positive cells and the increase in brain water content were significantly decreased in LIP+brain ischemic insult group compared with that in brain ischemic insult group, indicated that LIP prevented the occurrence of apoptosis of pyramidal neurons of the CA1 hippocampus and brain edema induced by brain ischemic insult. Pretreatment with SB 203580, an inhibitor of mitogen activated protein kinase p38(p38 MAPK), significantly increased the number of TUNEL-positive cells and brain water in SB 203580+LIP+brain ischemic insult group compared with that in DMSO+LIP+brain ischemic insult group, indicated that SB 203580 blocked the protection of LIP against neuronal apoptosis in the CA1 hippocampus and brain edema. CONCLUSION LIP could attenuate pyramidal neurons apoptosis of the CA1 hippocampus and brain edema evoked by brain ischemia, which maybe related to the activation of p38 MAPK.