Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Pathology Department, Faculty of Medicine, Helwan University, Cairo, Egypt.
J Food Biochem. 2022 Sep;46(9):e14217. doi: 10.1111/jfbc.14217. Epub 2022 May 11.
This study aimed to evaluate the potential neuroprotective effects of ketogenic diet (KD) against the neuronal disruptions induced by SE in lithium-pilocarpine rat model of status epilepticus (SE). Four groups of female rats include; groups I and III received standard diet and groups II and IV received KD for 3 weeks. Groups I and II were left untreated, while groups III and IV were injected with LiCl (127 mg/kg, i.p.) followed by pilocarpine HCl (10 mg/kg, i.p.) 18-24 h later, repeatedly, till induction of SE. 72 h post-SE, KD effectively ameliorated the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters and the oxidative stress indices, increased adenine nucleotides and decreased immunoreactivity of iNOS, TNFα, glial fibrillary acidic protein, and synaptophysin. Thiswas in association with improvement in inflammatory response and neuronal tissue characteristics in hippocampus of SE rats. Histological changes showed preservation of neuronal integrity. These findings highlight the protective effects of KD in the acute phase post-SE via ameliorating biochemical and histological changes involved. PRACTICAL APPLICATIONS: Epilepsy is the fourth most common neurological disorder that requires lifelong treatment. It stigmatizes patients and their families. The use of the ketogenic diet (KD) as a therapy for epilepsy developed from observations that fasting could reduce seizures. From 1920s, the KD was a common epilepsy treatment until it was gradually superseded by anticonvulsant drugs so that by the 1980s it was rarely used. However, there has been a resurgence of interest and usage of the KD for epilepsy since the turn of the century. Despite its long history, the mechanisms by which KD exhibits its anti-seizure action are not fully understood. Our study aims to identify the mechanism of KD which may help further studies to achieve the same benefits with a drug or supplement to overcome its unpalatability and gastrointestinal side effects.
这项研究旨在评估生酮饮食（KD）对锂-匹罗卡品癫痫持续状态（SE）大鼠模型中神经元紊乱的潜在神经保护作用。四组雌性大鼠包括：I 组和 III 组接受标准饮食，II 组和 IV 组接受 KD 饮食 3 周。I 组和 II 组未进行治疗，而 III 组和 IV 组在 18-24 小时后分别接受腹腔注射氯化锂（127mg/kg）和匹罗卡品盐酸盐（10mg/kg），直到 SE 发作。SE 后 72 小时，KD 有效改善了兴奋性（谷氨酸）和抑制性（GABA）神经递质之间的平衡，以及氧化应激指标，增加了腺嘌呤核苷酸，降低了 iNOS、TNFα、胶质纤维酸性蛋白和突触小体蛋白的免疫反应性。这与 SE 大鼠海马区炎症反应和神经元组织特征的改善有关。组织学变化显示神经元完整性得到了保存。这些发现强调了 KD 在 SE 后急性期通过改善涉及的生化和组织学变化来发挥保护作用。实际应用：癫痫是第四种最常见的神经系统疾病，需要终身治疗。它给患者及其家庭带来耻辱。生酮饮食（KD）作为癫痫治疗方法的使用源于观察到禁食可以减少癫痫发作。从 20 世纪 20 年代开始，KD 是一种常见的癫痫治疗方法，直到它逐渐被抗惊厥药物取代，以至于到 20 世纪 80 年代，它很少使用。然而，自本世纪初以来，KD 对癫痫的兴趣和使用再次兴起。尽管 KD 有很长的历史，但它发挥抗惊厥作用的机制尚未完全了解。我们的研究旨在确定 KD 的作用机制，这可能有助于进一步的研究，通过药物或补充剂来达到同样的效果，以克服其口感不佳和胃肠道副作用。
