Different ketogenesis strategies lead to disparate seizure outcomes
Different ketogenesis strategies lead to disparate seizure outcomes
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DOI：
10.1016/j.eplepsyres.2018.04.011
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发表时间：
2018-07-01
影响因子：
2.2
通讯作者：
Hartman, Adam L.
中科院分区：
文献类型：
--
作者：
Dolce, Alison;Santos, Polan;Hartman, Adam L.
背景：尽管在过去 50 年里推出了治疗癫痫的新药，但癫痫发作控制不佳的患者数量仍然没有变化。对于这一人群来说，基于代谢的疗法是一种未得到充分利用的治疗选择。我们假设两种不同的系统酮症方法，即生酮饮食和间歇性禁食，其急性癫痫发作测试曲线和线粒体呼吸会有所不同。方法：使用四种饮食方案之一喂养雄性 NIH 瑞士小鼠（3-4 周龄）12-13 天：生酮饮食 (KD)、与 KD 蛋白质含量和微量营养素 (CD) 相匹配的对照饮食或 CD 间歇性禁食（24 小时喂养/24 小时禁食） (CD-IF)，经过喂食后或禁食后测试。小鼠接受 6 HZ 阈值测试，或者在单独的队列中，根据其体重注射红藻氨酸（队列 I）或无论体重如何均一剂量（队列 II）。在同样喂养的癫痫幼稚小鼠的脑组织中测试线粒体呼吸。结果：KD 小鼠可以免受 6 Hz 诱导的癫痫发作，但在红藻氨酸测试（队列 I 和 II）中具有更严重的癫痫评分，这与 CD-IF 小鼠相反。饮食方案之间的线粒体呼吸没有差异。解释：KD 和 CD-IF 不具有相同的抗癫痫机制。这些差异不能用线粒体呼吸的差异来解释。尽管如此，KD 和 CD-IF 方案均可预防不同类型的癫痫发作，这表明应进一步探索 CD-IF 癫痫发作保护的机制。
Background: Despite the introduction of new medicines to treat epilepsy over the last 50 years, the number of patients with poorly-controlled seizures remains unchanged. Metabolism-based therapies are an underutilized treatment option for this population. We hypothesized that two different means of systemic ketosis, the ketogenic diet and intermittent fasting, would differ in their acute seizure test profiles and mitochondrial respiration.Methods: Male NIH Swiss mice (aged 3-4 weeks) were fed for 12-13 days using one of four diet regimens: ketogenic diet (KD), control diet matched to KD for protein content and micronutrients (CD), or CD with intermittent fasting (24 h feed/24 h fast) (CD-IF), tested post-feed or post-fast. Mice were subject to the 6 HZ threshold test or, in separate cohorts, after injection of kainic acid in doses based on their weight (Cohort I) or a uniform dose regardless of weight (Cohort II). Mitochondria] respiration was tested in brain tissue isolated front similarly-fed seizure-naive mice.Results: KD mice were protected against 6 Hz-induced seizures but had more severe seizure scores in the kainic acid test (Cohorts I & II), the opposite of CD-IF mice. No differences were noted in mitochondria] respiratiori between diet regimens.Interpretation: KD and CD-IF do not share identical antiseizure mechanisms. These differences were not ex,plained by differences in mitochondrial respiration. Nevertheless, both KD and CD-IF regimens protected against different types of seizures, suggesting that mechanisms underlying CD-IF seizure protection should be explored further.