Effects of Hypothermia on apoptosis and the expression of APE/Ref-1 following transient forebrain ischemia in rat

[Objective] To explore the neuroprotective mechanism of mild hypothermia by studying the effects of mild hypothermia on the expression of APE/Ref-1 and neuronal apoptosis in the hippocampal CA1 subregion after transient global cerebral ischemia in rats.[Methods] A model of transient global cerebral ischemia was made by 10min of bilateral common carotid artery occlusion and hypotension in rat.Expression of the APE/Ref-1 protein was detected by immunohistochemical analysis.Apoptosis after global ischemia was observed with TUNEL.[Results] Immunohisto-chemistry showed the nuclear expression of APE/Ref-1 in the control brains.Nuclear decreasing immunoreactivity of APE/Ref-1 started at 1st day and became significantly at 2nd day and the TUNEL positive neurons were observed at 2nd day and became significant at 3rd day in the hippocampal CA1 subregion after transient global ischemia in normothermic group.Mild hypothermic ischemic group was less decreased in nuclear immunoreactivity of APE/Ref-1(P0.01) and less quantity of apoptotic neurons(P0.01) than those of normothermic group.Double staining with APE/Ref-1 and TUNEL clearly showed that the neurons which lost APE/Ref-1 immunoreactivity became TUNEL positive.[Conclusions] The mild hypothermia had remarkable neuroprotection action.The inhibition of APE/Ref-1 reduction and ischemic neuronal apoptosis were assumed to be a neuroprotective mechanism of mild hypothermia.