惊厥性和非惊厥性癫痫持续状态对大鼠学习记忆功能的影响

目的 探讨惊厥性和非惊厥性癫痫持续状态发作对大鼠学习记忆功能的影响及其海马磷酸化的环磷腺苷反应元件结合蛋白(pCREB)的表达变化.方法 戊四氮点燃大鼠惊厥性癫痫持续状态(SE)和非惊厥性癫痫持续状态(GNCSE)两种动物模型,采用水迷宫和交替电刺激Y迷宫试验观察致痫后大鼠学习记忆功能改变.免疫组化染色观察大鼠海马pCREB蛋白水平表达变化.结果 SE大鼠致痫后近期出现水迷宫逃避潜伏期延长(P＜0.05),平台象限游泳时间及其百分比降低(P＜0.05),穿越平台次数减少(P＜0.05);电Y迷宫错误次数增多(P＜0.05),而远期均恢复正常.GNCSE组大鼠在致痫后近期水迷宫部分时段逃避潜伏期延长(P＜0.05),而平台象限游泳时间及其百分比和穿越平台次数与对照组相比均无明显差别(P＞0.05);电Y迷宫错误次数近期有所增加(P＜0.05).远期与对照组相比无明显差别.学习记忆功能下降的同时伴有海马组织pCREB蛋白水平表达的下降.结论 SE较GNCSE更易导致实验动物学习和记忆能力下降.无论哪种癫痫发作对学习记忆的影响均有一定的时限性.海马组织pCREB的表达变化可能参与了癫痫大鼠学习记忆功能改变的病理生理过程.

Changes in learning and memory functions in rats with status epilepticus and generalized nonconvulsive status epilepticus

OBJECTIVE: To observe the changes in the learning and memory functions and the hippocampal expression of phosphorylated cAMP response element-binding protein (pCREB) in rats with status epilepticus and generalized nonconvulsive status epilepticus. METHODS: Status epilepticus (SE) and generalized nonconvulsive status epilepticus (GNCSE) was induced by pentylenetetrazol kindling in SD rats, and the learning and memory function changes of the kindled rats were assessed by means of Morris water-maze test and Y-maze test with alternative electric stimulation. Immunocytochemistry was used for analysis pCREB protein expression in the hippocampus of the rats. RESULTS: In Morris water-maze test, the rats with SE showed prolonged mean escape latency (P<0.05), shortened swimming time in the platform quadrant (P<0.05), and reduced number of times of platform crossing (P<0.05) in the short term after kindling. But these changes were reversed and became normal a month after the kindling (P>0.05). In the Y-maze test with alternative electric stimulation, the total error (TE) of SE rats increased significantly in the short term after epilepsy (P<0.05), but recovered the normal level a month after kindling (P>0.05). The GNCSE rats showed prolonged mean escape latency at only certain time periods (P<0.05) in the short term, but with swimming time in the platform quadrant and number of platform crossings similar to the control group (P>0.05). The short-term TE of GNCSE rats increased significantly (P<0.05), but in the long term, TE was similar to that in the control group (P>0.05). The expression of pCREB decreased significantly in SE group in comparison with the control group in the short term. CONCLUSION: Epileptic seizures can lead to learning and memory function impairment in rats, and SE seems to cause greater impact than GNCSE on the learning and memory functions. pCREB might be involved in the pathophysiology of learning and memory deficit in epileptic rats.