Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

Si,Jianping; Wang,Shaohui; Liu,Ning; Yang,Xiaofei; Wang,Ying; Li,Ling; Wang,Jiwen; Lv,Xin

doi:10.3892/etm.2017.4552

Anticonvulsant effect of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy

Authors:
- Jianping Si
- Shaohui Wang
- Ning Liu
- Xiaofei Yang
- Ying Wang
- Ling Li
- Jiwen Wang
- Xin Lv
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Affiliations: 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 Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33606, USA, Institute of Pediatric Research, Qilu Children's Hospital of Shandong University, Jinan, Shandong 250022, P.R. China, Department of Pediatrics, Yidu Central Hospital, Weifang, Shandong 262500, P.R. China, Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China
Published online on: June 7, 2017 https://doi.org/10.3892/etm.2017.4552
Pages: 765-770

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Abstract

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.

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