Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Eur Rev Med Pharmacol Sci. 2018 Jan;22(1):250-261. doi: 10.26355/eurrev_201801_14126.
Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats.
Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression.
OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (p<0.05). OXC administration causes histological changes of neurocytes. OXC 281.25 mg/kg or more concentration significantly decreased neurocytes counts and increased TUNEL-staining positive neurocytes compared to Control group (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased caspase 3 activity compared to Control group in P5 rats (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased Bax, Bax/Bcl-2 ratio and cytochrome C release in frontal lobes compared to Control group in P5 rats (p<0.05).
Oxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.
抗癫痫药物（AEDs）是治疗新生儿癫痫的主要方法；然而，一些 AEDs 可能会导致新生儿大脑发育受损。本研究旨在探讨奥卡西平（OXC）对新生大鼠大脑发育损伤的影响。
新生和成年大鼠均分为 6 组，包括对照组、OXC187.5mg/kg 组、OXC281.25mg/kg 组、OXC375mg/kg 组、LEV 组和 PHT 组。评估体重和脑重。使用苏木精和伊红（HE）和尼氏染色分别观察神经细胞形态和尼氏小体。使用 TUNEL 检测法检测细胞凋亡，使用分光光度计法评估半胱氨酸天冬氨酸蛋白酶 8（caspase 8）活性。使用流式细胞术评估细胞色素 C 释放。使用 Western blot 检测 Bax 和 Bcl-2 表达。
与对照组相比，OXC375mg/kg 治疗组新生大鼠（P5 大鼠）的脑重显著降低（P<0.05）。OXC 给药导致神经细胞的组织学变化。与对照组相比，OXC281.25mg/kg 或更高浓度显著减少神经细胞计数并增加 TUNEL 染色阳性神经细胞（P<0.05）。与对照组相比，OXC281.25mg/kg 和 OXC375mg/kg 使 P5 大鼠的 caspase 3 活性显著增加（P<0.05）。与对照组相比，OXC281.25mg/kg 和 OXC375mg/kg 使 P5 大鼠额叶的 Bax、Bax/Bcl-2 比值和细胞色素 C 释放显著增加（P<0.05）。
奥卡西平在 281.25mg/kg 或更高浓度下通过触发 Bax/Bcl-2 信号通路介导 caspase 3 激活，导致新生大鼠神经细胞凋亡和大脑发育损伤。
