Effects of Valproate on Cognitive Function Recovery and Neuron Regeneration of Hippocampus in Mice After Global Cerebral Ischemia

OBJECTIVE To study the effect of valproate(VPA) on cognitive function recovery and hippocampal neuron regeneration after global cerebral ischemia (GCI) in mice and its mechanism. METHODS Forty eight mice were randomly divided into 4 groups:sham group, VPA group, GCI group, GCI+VPA group, 12 mice in each group. GCI group and GCI+VPA group were drew blood and bilateral common carotid artery occlusion of 20 min. The sham group and VPA group were only treated with incision and suture. After operation, VPA group and GCI+VPA group were intraperitoneal injection 30 mg·kg^-1·d^-1 for 7 d, sham group and VPA group were given the same dose of saline. The changes in cognitive functions such as spatial learning and memory were tested by the selective T maze test. Nissl staining was used to observe the morphological changes in the hippocampal neurons of CA1 in mice; the number of DCX⁺ cells in the dentate gyrus(DG) region of the hippocampus in mice was observed by immunofluorescence; the expression of nNOS and GAP-43 in hippocampus of the hippocampus were detected by Western blot. RESULTS The correct selection rate of VPA treated mice in the selective T maze after GCI was higher than that in the saline treatment group, and the density of neurons in hippocampal CA1 area in VPA treated mice was higher than that of the saline treatment group, and VPA treated mice DG region DCX positive cells were increased. Compared with the Saline treatment group, the difference was statistically significant (P<0.05). At the same time, the expression level of nNOS in the hippocampus of GCI mice was down regulated by VPA treatment, and the expression of GAP-43 was up. The difference was statistically significant (P<0.05). CONCLUSION VPA can promote the neuroprotective effect and promote the regeneration of neurons after GCI in mice, which can improve the cognitive function of GCI. The mechanism may be related to the inhibition of nNOS related signaling pathway and the promotion of GAP-43 expression.