Si Jianping, Wang Shaohui, Liu Ning, Yang Xiaofei, Wang Ying, Li Ling, Wang Jiwen, Lv Xin
Department of Neurology, Children's Medical Center, Qilu Hospital of Shandong University, Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Pediatrics, The People's Hospital of Guangrao, Dongying, Shandong 257300, P.R. China.
Exp Ther Med. 2017 Jul;14(1):765-770. doi: 10.3892/etm.2017.4552. Epub 2017 Jun 7.
The present study aimed to investigate the anticonvulsant effects of β-hydroxybutyrate (BHB) in a kainic acid (KA)-induced rat seizure model. The concentrations of BHB and glucose were detected in the blood prior to exogenous BHB administration. Three different doses of BHB (2, 4 and 8 mmol/kg) were then injected into male Wistar rats intraperitoneally, and the concentrations of BHB and glucose in the blood were detected. Rats received 0.9% normal saline intraperitoneally at a dose of 4 ml/kg as a control. Subsequently, a KA-induced rat seizure model was established and the anticonvulsant effects of BHB were investigated. The onset time of seizure and the degree of seizure behavior were recorded. Nissl and Timm staining were used to evaluate neuronal loss and mossy fiber sprouting, respectively. The present study demonstrated that exogenous BHB administration could significantly increase BHB concentration in the blood and this concentration was maintained for 90 min without affecting blood glucose levels. Furthermore, it was determined that a dose of 4 mmol/kg BHB is optimal for exogenous administration. The onset time of seizure was significantly prolonged in BHB-pretreated rats (63.31±4.050 min) compared with the control group (37.08±1.958 min; P=0.039). In addition, neuronal loss and mossy fiber sprouting were both alleviated in the BHB-pretreated model group. Exogenous BHB administration at a dose of 4 mmol/kg may be an alternative to a ketogenic diet to exert a protective effect in the epileptic model induced by KA. The results of the present study may allow novel therapeutic strategies to be developed to treat epilepsy.
本研究旨在探讨β-羟基丁酸（BHB）在 kainic 酸（KA）诱导的大鼠癫痫模型中的抗惊厥作用。在给予外源性 BHB 之前，检测血液中 BHB 和葡萄糖的浓度。然后将三种不同剂量的 BHB（2、4 和 8 mmol/kg）腹腔注射到雄性 Wistar 大鼠体内，并检测血液中 BHB 和葡萄糖的浓度。大鼠腹腔注射 4 ml/kg 的 0.9%生理盐水作为对照。随后，建立 KA 诱导的大鼠癫痫模型，并研究 BHB 的抗惊厥作用。记录癫痫发作的起始时间和癫痫行为的程度。分别使用 Nissl 染色和 Timm 染色来评估神经元丢失和苔藓纤维发芽。本研究表明，外源性给予 BHB 可显著提高血液中 BHB 的浓度，且该浓度可维持 90 分钟，而不影响血糖水平。此外，确定 4 mmol/kg 的 BHB 剂量最适合外源性给药。与对照组（37.08±1.958 分钟；P = 0.039）相比，BHB 预处理的大鼠癫痫发作起始时间显著延长（63.31±4.050 分钟）。此外，BHB 预处理的模型组中神经元丢失和苔藓纤维发芽均得到缓解。以 4 mmol/kg 的剂量外源性给予 BHB 可能是生酮饮食的一种替代方法，可在 KA 诱导的癫痫模型中发挥保护作用。本研究结果可能有助于开发治疗癫痫的新治疗策略。
