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29 December 2016 : Animal Research

Effect of Sodium Valproate on Cognitive Function and Hippocampus of Rats After Convulsive Status Epilepticus

Peng Wu1ABCE, Siqi Hong1BD, Min Zhong1BD, Yi Guo1AEF, Hengsheng Chen2AEF, Li Jiang1234ABCDE*

DOI: 10.12659/MSM.898859

Med Sci Monit 2016; 22:5197-5205

Abstract

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.

Keywords: Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism, Animals, Cognition - drug effects, Excitatory Postsynaptic Potentials - drug effects, Hippocampus - physiopathology, Learning - drug effects, Long-Term Potentiation - drug effects, Memory, Short-Term - drug effects, Phosphorylation - drug effects, Rats, Wistar, Seizures - physiopathology, Spatial Memory - drug effects, Valproic Acid - therapeutic use

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750