Effects of combination of mild head hypothermia and inhibition of PTEN activity preconditioning on global cerebral ischemia - reperfusion injury in rats
Objective To investigate the effects of mild head hypothermia and combination of inhibition of PTEN activity preconditioning on global cerebral ischemia - reperfusion injury in rats. Methods Sixty healthy male Wistar rats weighing 250 ~ 280 g were randomly divided into five groups (n = 12 each): group I sham operation (S); group Ⅱ global cerebral ischemia -reperfusion injury (IR); group Ⅲ inhibition of PTEN activity preconditioning (B); group Ⅳ mild hypothermia preconditioning (MH) and group V combination of inhibition of PTEN activity and mild hypothermia preconditioning (MB). Global cerebral ischemia - reperfusion was produced by modified Pulsinelli' s four - vessel occlusion for 15 min followed by 8 h reperfusion in groups Ⅱ ~ V. Global cerebral ischemia was confirmed by isoelectric EEG,dilated pupil and pale conjunctiva. In group III and V BPV (pic) was given intraperitoneally before global cerebral ischemia while in group Ⅱ and Ⅳ rats were given an equal volume normal saline. In group IV and V nasopharyngeal cooling was applied to reduce head temperature before global cerebral ischemia. In group I alar foramina and common carotid arteries were exposed but no cerebral ischemia was performed. At the end of 8 h reperfusion,six rats were killed in each group for determination of expression of P - PTEN, Bax and Bcl - 2,MDA content and SOD activity. Results Inhibition of PTEN activity, mild hypothermia and their combination increased the expression of P - PTEN and Bcl - 2/Bax ratio and decreased MDA content. Expression of P - PTEN and Bcl -2/Bax ratio were significantly higher while MDA content was significantly lower and SOD activity was significantly higher in group MB than that in group B or group MH. Conclusion Inhibition of PTEN activity preconditioning, mild hypothermia preconditioning and their combination all can alleviate global ischemia - reperfusion injury in rats and all have neuroprotective effect. Combination of inhibition of PTEN activity and mild head hypothermia has more enhanced neuroprotective effect than either used alone. Inhibition of apoptosis and clearing of reactive oxygen species play a vital role in the protective effects.