Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, United States.
Department of Neurosurgery, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, United States; Department of Neurosurgery, New Jersey Medical School, Rutgers University, Newark, NJ 07102, United States; Rutgers Neurosurgery H.O.P.E. Center, Department of Neurosurgery, Rutgers University, New Brunswick, NJ 08901, United States.
Epilepsy Res. 2020 Nov;167:106444. doi: 10.1016/j.eplepsyres.2020.106444. Epub 2020 Aug 19.
High fat, low carbohydrate ketogenic diets (KD) have been in use for the treatment of epilepsy for almost a hundred years. Remarkably, seizures that are resistant to conventional anti-seizure drugs can in many cases be controlled by the KD therapy, and it has been shown that many patients with epilepsy become seizure free even after discontinuation of the diet. These findings suggest that KD combine anti-seizure effects with disease modifying effects. In addition to the treatment of epilepsy, KDs are now widely used for the treatment of a wide range of conditions including weight reduction, diabetes, and cancer. The reason for the success of metabolic therapies is based on the synergism of at least a dozen different mechanisms through which KDs provide beneficial activities. Among the newest findings are epigenetic mechanisms (DNA methylation and histone acetylation) through which KD exerts long-lasting disease modifying effects. Here we review mechanisms through which KD can affect neuroprotection in the brain, and how a combination of those mechanisms with epigenetic alterations can attenuate and possibly reverse the development of epilepsy.
高脂肪、低碳水化合物生酮饮食（KD）已用于治疗癫痫近一百年。值得注意的是，KD 疗法可控制对传统抗癫痫药物耐药的癫痫发作，并且已经表明许多癫痫患者即使在停止饮食后也可停止发作。这些发现表明 KD 将抗癫痫作用与疾病修饰作用相结合。除了治疗癫痫，KD 现在还广泛用于治疗各种疾病，包括减肥、糖尿病和癌症。代谢疗法成功的原因基于至少十几种不同机制的协同作用，KD 通过这些机制提供有益的活动。最新发现之一是通过 KD 发挥持久疾病修饰作用的表观遗传机制（DNA 甲基化和组蛋白乙酰化）。在这里，我们综述 KD 影响大脑神经保护的机制，以及这些机制与表观遗传改变的结合如何减轻和可能逆转癫痫的发展。
