癫痫发作对幼鼠及成鼠远期认知功能和海马神经发生的影响

Effects of epileptic seizure on the long- term cognitive function and hippocampal neurogenesis in juvenile and matured rats

目的观察癫痫发作对幼鼠及成鼠远期认知功能及海马神经发生的影响。方法将3周龄和成年雄性SD大鼠,以氯化锂-匹罗卡品药物造模,根据取脑组织时间分为幼鼠及成鼠2周实验组、4周实验组,并设相应的对照组。利用Morris水迷宫观察4周组的认知功能;BrdU标记后,免疫荧光染色和激光共聚焦显微技术比较幼鼠及成鼠2周组海马齿状回颗粒细胞层神经细胞的增殖、4周组新生细胞的分化。结果水迷宫实验显示幼鼠及成鼠4周实验组的潜伏期均较对照组延长(P<0.05),成鼠较幼鼠延长更为明显。幼鼠2、4周实验组海马齿状回颗粒细胞层BrdU阳性细胞增殖数均高于对照组(P<0.05);成鼠2、4周实验组均低于相应对照组(P<0.05)。结论癫痫发作可导致认知功能下降,成鼠比幼鼠下降明显;癫痫发作使幼鼠海马齿状回颗粒细胞层神经细胞的增殖增加,使成鼠的增殖降低。

Objective To observe the effects of epileptic seizure on the long- term cognitive function and hippocampal neurogenesis in juvenile and matured rats. Methods Lithium- pilocarpine（ LI- PILO） was administered to three- week- old and matured male Sprague-Dawley rats to induce epileptic seizure. After successfully induced epileptic seizure,the rats were randomly divided into eight groups according to the time points of bromodeoxyuridine（ BrdU） injection： 2 weeks group,4 weeks group and control groups. Morris water maze was used to compare the cognitive function of 4 weeks group of juvenile and matured rats. By using immunohistochemistry method,the expressions of the BrdU in the granular layer of DG in 2 weeks group and the differentiation of new nerve cells in 4 weeks group of juvenile and matured rats were observed under a laser confocal microscope. Results The incubation period in 4 weeks group of juvenile and matured rats were significantly longer than those in control groups（ P 0. 05）,and the incubation period in matured rats was much more obvious longer than those in juvenile rats in Morris water maze. The BrdU positive cells in 2 weeks group and 4 weeks group of juvenile rats were more than those in their control groups（ P 0. 05）. The BrdU positive cells in 2 weeks group and 4 weeks group of matured rats were lower than those in their control groups（ P 0. 05）. Conclusion Epileptic seizure can decrease the cognitive function and those of the matured rats decreased obviously than the juvenile rats. Epileptic seizure can increase the proliferation of neurons in the granular layer of hippocampal DG in the juvenile rats,while decrease the proliferation of neurons in matured rats.