The effect of local mild hypothermia on neuronal apoptosis following focal cerebral ischemia in rats

Objective To study the effect of local mild hypothermia on Bax、Bcl-2、Cyt C and caspase-3 protein expression after focal cerebral ischemia in rats,and to disclose the mechanism of neuroprotection by mild hypothermia. Methods Permanent middle cerebral artery occlusion (MCAO) was induced in Wistar rats. Intraischemic local mild hypothermia was applied for 2 hours (33℃) in the hypothermia group (HT). Normal body temperature was maintained (37℃) in the normothermia group (NT). After survival period of 2h,6h,12h,24h,3d,1w and 2w,the rats were anesthetized and the brains were removed. Hematoxylin eosin staining was used to identify cerebral infarcts. Immunohistochemical analysis was used to detect expression of Bax、Bcl-2、Cyt C and caspase-3. Results The immunoreactivity of Bcl-2,Bax,Cyt C and caspase-3 was detectable after 2-hour ischemia in the penumbra region,and was significantly increased after 24 hours,then decreased gradually. There was a few immunoreactivity positive neurons after 2 weeks. Immunoreactivity positive neurons of Bax,Cyt C and caspase-3were in ischemic core and penumbra. Bcl-2 was mainly expressed in the neuronal cytoplasm in the penumbra. Compared with HT group,Bcl-2 was significantly increased in HT group,and Bax,Cyt C and caspase-3 were significantly lower. The proportion of Bax to Bcl-2 was the lowest after 24h-ischemia in HT group. Conclusion Mild hypothermia increases expression of Bcl-2,and decrease expression of Bax,Cyt C and caspase-3.Mild hypothermia may interfere with protein synthesis. Mild hypothermia decreases the ratio of Bax/Bcl-2,then attenuates neuronal apoptosis.