The ketogenic diet inhibits epileptogenesis in EL mice: A genetic model for idiopathic epilepsy
The ketogenic diet inhibits epileptogenesis in EL mice: A genetic model for idiopathic epilepsy
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DOI：
10.1111/j.1528-1157.2000.tb00275.x
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发表时间：
2000-08-01
期刊：
影响因子：
5.6
通讯作者：
Seyfried, TN
中科院分区：
文献类型：
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作者：
Todorova, MT;Tandon, P;Seyfried, TN
目的：生酮饮食（KD）是一种高脂肪、低碳水化合物和低蛋白质的饮食，已被用于治疗儿童难治性癫痫发作超过75年。然而，关于KD如何抑制癫痫发作或其对癫痫发生的影响知之甚少。几种癫痫动物模型对KD治疗反应良好，但尚未在具有癫痫发作遗传易感性的动物中研究KD。在这里，我们研究了在EL小鼠，人类特发性epilepsy.Methods的动物模型KD的抗癫痫作用：年轻的雄性EL小鼠（出生后30天）随机分为两组，自由进食KD（治疗，n = 21）或Agway的食物（对照，n = 19）。每周一次对小鼠称重并测试癫痫发作，共10周。在整个研究期间的几个时间点分析KD对血浆酮体和葡萄糖水平的影响。关联学习之间进行了比较治疗和对照动物使用水迷宫.Results：KD治疗延迟癫痫发作的年轻男性EL小鼠1个月，然而，癫痫发作的保护是短暂的，因为治疗和对照小鼠经历了类似的数量和强度的癫痫发作后6周的饮食。治疗组和对照组的血糖水平和联想学习相似，但KD小鼠的血浆β-羟基丁酸水平显著较高。然而，酮病的水平，在EL mice.Conclusion：KD延迟癫痫发作在EL小鼠，这表明对癫痫发生短暂的保护癫痫发作的保护。KD不影响血糖水平或联想学习。因此，EL小鼠可作为研究KD抗癫痫机制的良好模型。
Purpose: The ketogenic diet (KD) is a high-fat, low-carbohydrate and -protein diet that has been used to treat refractory seizures in children for more than 75 years. However, little is known about how the KD inhibits seizures or its effects on epileptogenesis. Several animal models of epilepsy have responded favorably to KD treatment, but the KD has not been studied in animals with a genetic predisposition to seizures. Here we studied the antiepileptogenic effect of the KD in EL mice, an animal model for human idiopathic epilepsy.Methods: Young male EL mice (postnatal day 30) were randomly separated into two groups fed ad libitum with either the KD (treated, n = 21) or Agway chow (control, n = 19). The mice were weighed and tested for seizures once per week for a total of 10 weeks. The effects of the KD on plasma levels of ketone bodies and glucose were analyzed at several time points throughout the study. Associative learning was compared between treated and control animals using a water maze.Results: KD treatment delayed seizure onset in young male EL mice by 1 month; however, seizure protection was transient, inasmuch as the treated and control mice experienced a similar number and intensity of seizures after 6 weeks on the diet. Plasma glucose levels and associative learning were similar in the treated and control groups, but the plasma beta-hydroxybutyrate levels were significantly higher in mice on the KD. The level of ketosis, however, was not predictive of seizure protection in EL mice.Conclusion: The KD delayed seizure onset in EL mice, suggesting a transient protection against epileptogenesis. The KD did not influence plasma glucose levels or associative learning. Therefore, the EL mouse may serve as a good model to study the antiepileptogenic mechanisms of the KD.