Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, CA, Canada.
Department of Cell Biology and Anatomy, Hotchkiss Brain Institute, and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, CA, Canada.
Neurobiol Dis. 2021 Jul;154:105335. doi: 10.1016/j.nbd.2021.105335. Epub 2021 Mar 17.
A prolonged vasoconstriction/hypoperfusion/hypoxic event follows self-terminating focal seizures. The ketogenic diet (KD) has demonstrated efficacy as a metabolic treatment for intractable epilepsy and other disorders but its effect on local brain oxygen levels is completely unknown. This study investigated the effects of the KD on tissue oxygenation in the hippocampus before and after electrically elicited (kindled) seizures and whether it could protect against a seizure-induced learning impairment. We also examined the effects of the ketone β-hydroxybutyrate (BHB) as a potential underlying mechanism.
Male and female rats were given access to one of three diet protocols 2 weeks prior to the initiation of seizures: KD, caloric restricted standard chow, and ad libitum standard chow. Dorsal hippocampal oxygen levels were measured prior to initiation of diets as well as before and after a 10-day kindling paradigm. Male rats were then tested on a novel object recognition task to assess postictal learning impairments. In a separate cohort, BHB was administered 30 min prior to seizure elicitation to determine whether it influenced oxygen dynamics.
The KD increased dorsal hippocampal oxygen levels, ameliorated postictal hypoxia, and prevented postictal learning impairments. Acute BHB administration did not alter oxygen levels before or after seizures.
The ketogenic diet raised brain oxygen levels and attenuated severe postictal hypoxia likely through a mechanism independent of ketosis and shows promise as a non-pharmacological treatment to prevent the postictal state.
自限性局灶性癫痫发作后会出现血管收缩/灌注不足/缺氧事件。生酮饮食（KD）已被证明是治疗难治性癫痫和其他疾病的有效代谢疗法，但它对局部脑氧水平的影响尚完全未知。本研究旨在探讨 KD 在电诱发（点燃）癫痫发作前后对海马组织氧合的影响，以及它是否可以预防癫痫发作引起的学习障碍。我们还研究了酮体β-羟丁酸（BHB）作为一种潜在的潜在机制的作用。
雄性和雌性大鼠在癫痫发作开始前 2 周接受三种饮食方案之一：KD、热量限制的标准饲料和自由摄取的标准饲料。在开始饮食之前以及在 10 天的点燃范式之前和之后测量背侧海马氧水平。然后，雄性大鼠接受新物体识别任务测试，以评估癫痫后学习障碍。在另一队列中，在诱发癫痫前 30 分钟给予 BHB，以确定它是否影响氧动力学。
KD 增加了背侧海马的氧水平，改善了癫痫后缺氧，并预防了癫痫后学习障碍。急性 BHB 给药不会改变癫痫发作前后的氧水平。
生酮饮食提高了大脑的氧水平，并减轻了严重的癫痫后缺氧，这可能是通过一种与酮症无关的机制实现的，并有望成为预防癫痫后状态的非药物治疗方法。
