Effect Of Mild Hypothermia On Hippocampal Expression Of Nestin And Caspase-3After Cerebral Ischemia Reperfusion In Rats

Objective:In this study, SD rats are subjected to middle cerebral artery occlusion (MCAO) according to method of Longa. Then we practice hypothermia on cerebral ischemic rats and observe neurological deficit score, volume of cerebral infarction, the expression of nestin and caspase-3in brain tissue, in order to explore neuroprotective mechanism of hypothermia.Methods:144adult SD rats weighing250to300g were subjected to2-hour transient middle cerebra artery occlusion (MCAO) and divided randomly into three groups, there were sham group, ischemia/reperfusion model+normal body temperature group and ischemia/reperfusion model+hypothermia group. Every group was objected at four time points after ischemia/reperfusion:1d,3d,7d and14d. Animals of sham group and ischemia/reperfusion model+normal body temperature group were not carried out cooling therapy and the rectum temperature of rats was maintained at36.8-37.2℃. Animals of ischemia/reperfusion model+hypothermia group were carried out cooling therapy for4hours and the rectum temperature of rats was maintained at33～35℃.Then neurological deficit score, volume of cerebral infarct, the expression of nestin and caspase-3were detected at each time point.Results:1. The results of neurological deficit scores show:We did not observe the phenomenon of neurological deficit in sham animals. The neurological deficit scores in normothermic group and hypothermia group were observed, and there were significant differences among two groups (P<0.05), except1d group (P>0.05)2. Volume of cerebral infarct:No infarcts were observed in sham animals. Normothermic animals had larger size of infarct than therapy of hypothermia. For four time points, there were significant differences among two groups (P<0.05).3. Expression of nestin:The expression of nestin in sham group was low. In normothermic group and hypothermia group, amount of nestin positive cells were high and increased at1d, peaked at3d, and decreased at7d and14d. There were significant differences among two groups at1d and3d (P<0.05)4. Result of caspase-3:there was a small amount of caspase-3positive cells in sham group. In normothermic group and hypothermia group, we can observe that the expression of caspase-3increased at Id, and decreased at3d,7d and14d. There were significant differences among two groups (P<0.05), except at14d after ischemic reperfusion (P>0.05). Conclusions:1. Neurological deficit score and volume of cerebral infarction were reduced after therapy of mild hypothermia (33～35℃). And mild hypothermia treatment can promote the expression of nestin and decrease the expression of caspase-3.2. Neuroprotection of mild hypothermia (33～35℃) may contribute to increase of the expression of nestin and decrease the expression of caspase-3after cerebral ischemia reperfusion.