Effects Of Different Duration Of Global Cerebral Ischemia And Reperfusion On JNK Pathway And Neuronal Injury In Rat Hippocampus

Objective To explore the expression change of the c-Jun N-terminal kinase(JNK)and p-JNK in hippocampus after prolonged global cerebral ischemia or reperfusion in rats, and ischemia/reperfusion induced hippocampal neuronal death.Methods Transient global cerebral ischemia was induced by four-vessel occlusion method.The SD rats weighing 250-320g were randomly divided into 3 groups:the sham group,the ischemia group and the ischemia/reperfusion group.The rats were sacrificed at 5 min,10 min,15 min,20 min,30 min of global ischemia and at 10 min, 30 min,1 h,2 h,4 h,6 h,8 h,12 h,24 h,48 h,72 h of reperfusion after 20-min global ischemia.The expression of JNK and p-JNK was examined by Western blot.The surviving neurons in hippocampal CA1 area were counted by HE staining after 10-min ischemia or 20 min of ischemia and 7 days of reperfusion.Results 10-min ischemia and 7 days of reperfusion or 20-min ischemia and 7 days of reperfusion destroyed 82%and 99%of CA1 hippocampal neurons,respectively.The expression of JNK increased after 10 min of ischemia,and the peak appeared at 20 min of ischemia;the expression of JNK in the ischemia/reperfusion group appeared two peaks,with an initial peak at 6 h of reperfusion,and a second,larger peak at 12 h of reperfusion.The peak for the expression of p-JNK in the ischemia/reperfusion group appeared at 1 h of reperfusion,then decreased a little,and peaked again at 12 h of reperfusion.Conclusions 20-min global ischemia destroyed more neurons than 10-min global ischemia.The high expression of JNK lasted longer and JNK activation occurred earlier and more severe after 20-min global cerebral ischemia.These results suggested JNK pathway played more harmful role in neuron death after long time ischemia.