Yum Mi-Sun, Ko Tae-Sung, Kim Dong Wook
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul;
Department of Pediatrics, Clinical Research Center, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
J Epilepsy Res. 2012 Dec 30;2(2):29-32. doi: 10.14581/jer.12008. eCollection 2012 Dec.
The ketogenic diet was formulated to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies. Recent research data suggest that the anticonvulsant efficacy of the KD may be due in part to the direct actions of ketone bodies. This study was designed to investigate the anticonvulsant effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in mature mice.
Eighty-two male ICR mice at postnatal day 49 were used. All mice were pretreated with scopolamine methylbromide prior to pilocarpine injection. Experimental mice (n=42) were injected intraperitoneally with BHB (20 mmol/kg) 15 min prior to pilocarpine administration, while control animals (n=40) with normal saline. Pilocarpine (300 mg/kg) was administered intraperitoneally and mice were monitored for 2 h after pilocarpine injection.
All mice developed typical seizure behaviors. The mean (±SD) latency to the onset of seizures was significantly prolonged in the BHB-treated mice compared with controls (4.83±1.95 min vs. 3.67±1.90 min, p<0.01).
This study demonstrates that treatment with BHB prolongs the latency to the onset of seizures induced by pilocarpine in mature mice and suggests that BHB, one of the ketone bodies, may have direct anticonvulsant effects.
生酮饮食旨在模拟禁食时出现的生化变化，特别是酮体的形成。近期研究数据表明，生酮饮食的抗惊厥疗效可能部分归因于酮体的直接作用。本研究旨在探讨β-羟基丁酸（BHB）对成熟小鼠毛果芸香碱诱导的癫痫发作的抗惊厥作用。
使用82只出生后第49天的雄性ICR小鼠。所有小鼠在注射毛果芸香碱前均用甲基溴化东莨菪碱预处理。实验小鼠（n = 42）在给予毛果芸香碱前15分钟腹腔注射BHB（20 mmol/kg），而对照动物（n = 40）注射生理盐水。腹腔注射毛果芸香碱（300 mg/kg），并在注射后对小鼠进行2小时监测。
所有小鼠均出现典型的癫痫发作行为。与对照组相比，BHB处理的小鼠癫痫发作开始的平均（±标准差）潜伏期显著延长（4.83±1.95分钟对3.67±1.90分钟，p<0.01）。
本研究表明，BHB治疗可延长成熟小鼠毛果芸香碱诱导的癫痫发作潜伏期，并提示酮体之一BHB可能具有直接抗惊厥作用。
