Sodium valproate suppresses abnormal neurogenesis induced by convulsive status epilepticus

作     者：Peng Wu Yue Hu Xiu-Juan Li Min Cheng Li Jiang 

作者机构：Department of Neurology Children's Hospital of Chongqing Medical University Chongqing International Science and Technology Cooperation Center for Child Development and Disorders Ministry of Education Key Laboratory of Child Development and Disorders Key Laboratory of Pediatrics in Chongqing 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2019年第14卷第3期

页      面：480-484页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 100215[医学-康复医学与理疗学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China for Youth Science Project No.81201507(to PW) 

主　　题：nerve regeneration status epilepticus sodium valproate long-term potentiation neural stem cells neurogenesis migration subgranular zone subventricular zone neural regeneration 

摘      要：Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.