Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies.
Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies.
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DOI：
10.1186/1743-7075-1-11
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发表时间：
2004-10-19
影响因子：
4.5
通讯作者：
Seyfried TN
中科院分区：
文献类型：
--
作者：
Mantis JG;Centeno NA;Todorova MT;McGowan R;Seyfried TN
高脂肪、低碳水化合物的生酮饮食(KD)被开发为一种替代禁食的癫痫治疗方法。虽然禁食和KD抑制癫痫发作的机制仍然是推测的，但可能与大脑能量代谢的变化有关。我们先前证明，限制热量(CR)通过降低癫痫EL小鼠的血糖来抑制癫痫敏感性，EL小鼠是人类多因素特发性癫痫的自然模型。在这项研究中，我们比较了KD和CR在成年EL小鼠活动期癫痫中的抗癫痫和抗惊厥作用。对反复发作至少15次复杂部分性发作的EL小鼠，分别给予标准饮食不限食(SD-UR)或限食(SD-R)，以及KD不限食(KD-UR)或限食(KD-R)。所有小鼠在开始饮食前禁食14小时。使用了一种新的实验设计，其中限制饮食的组中的每只小鼠作为自己的对照，以实现体重减轻20%-23%。在为期9周的治疗期间，每周测量一次癫痫敏感度、体重以及血糖和β-羟丁酸水平。在试验期间，SD-UR组和KD-UR组的体重和血糖水平保持在较高水平，但SD-R组和KD-R组的体重和血糖水平显著降低(p<；0.001)。SD-R组和KD-R组的血浆β-羟丁酸水平显著高于各自的UR组(p<；0.001)。在整个研究过程中，两个UR喂养组的癫痫敏感度都很高，但两个R喂养组的癫痫敏感度在三周后显著降低。结果表明，EL小鼠的癫痫敏感性依赖于血糖水平，癫痫的控制更多地与血糖水平有关，而不是与饮食卡路里的来源有关。此外，CR也是KD抗癫痫和抗惊厥作用的基础。从葡萄糖到酮体的能量转换被预测为通过抑制和兴奋神经系统的多个综合变化来管理癫痫发作。
The high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups. The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.