Wu Peng, Hong Siqi, Zhong Min, Guo Yi, Chen Hengsheng, Jiang Li
Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China (mainland).
Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China (mainland).
Med Sci Monit. 2016 Dec 29;22:5197-5205. doi: 10.12659/msm.898859.
BACKGROUND The aim of this study was to explore the effect and possible mechanism of sodium valproate (VPA) on the cognitive function and the hippocampus of rats after convulsive status epilepticus (CES). MATERIAL AND METHODS A rat model of CES was established and the Morris water maze was used to observe changes in the cognitive function of the rats after the administration of VPA. Acute hippocampal slices were made to detect field excitatory postsynaptic potential. Western blot analysis was used to test for the expression of CaMKII and p-CaMKII. RESULTS (1) CSE caused no spatial reference memory (SFM) or spatial working memory (SWM) damage to 15-day-old (P15) rats, but caused significant SRM and SWM damage to 35-day-old (P35) rats. VPA damaged the SRM and SWM of P15 rats in both the CSE and control groups. However, VPA improved the memory damage caused by CSE in P35 rats. (2) VPA treatment in vivo increased the induced success rate and the sustainable time of long-term potentiation (LTP) in P35 rats, and also inhibited the expression of CaMKII and p-CaMKII in both P15 and P35 rats. CONCLUSIONS VPA significantly improved spatial cognitive dysfunction in a CSE model of P35 rats, and damaged the spatial memory of normal P15 and P35 rats. Improvements after administration of VPA were closely related to the increase of induced success rate and the prolongation of the sustainable time of LTP. VPA treatment in vivo, which inhibited expression and phosphorylation of CaMKII, showed no obvious inhibition on LTP, which may be related to the elution effect of VPA.
背景 本研究旨在探讨丙戊酸钠（VPA）对惊厥性癫痫持续状态（CES）后大鼠认知功能及海马的影响及其可能机制。
材料与方法 建立CES大鼠模型，采用莫里斯水迷宫观察VPA给药后大鼠认知功能的变化。制作急性海马脑片检测场兴奋性突触后电位。采用蛋白质免疫印迹分析检测CaMKII和p-CaMKII的表达。
结果 （1）CSE对15日龄（P15）大鼠的空间参考记忆（SFM）和空间工作记忆（SWM）无损害，但对35日龄（P35）大鼠的SFM和SWM有显著损害。VPA对CSE组和对照组的P15大鼠的SFM和SWM均有损害。然而，VPA改善了P35大鼠CSE所致的记忆损害。（2）VPA体内治疗增加了P35大鼠长时程增强（LTP）的诱导成功率和持续时间，并且抑制了P15和P35大鼠CaMKII和p-CaMKII的表达。
结论 VPA显著改善了P35大鼠CSE模型中的空间认知功能障碍，损害了正常P15和P35大鼠的空间记忆。VPA给药后的改善与LTP诱导成功率的增加和持续时间的延长密切相关。VPA体内治疗抑制了CaMKII的表达和磷酸化，但对LTP无明显抑制作用，这可能与VPA的洗脱效应有关。
