腺苷和生酮治疗。,Journal of Caffeine and Adenosine Research

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腺苷和生酮治疗。
Journal of Caffeine and Adenosine Research Pub Date : 2020-09-16 , DOI: 10.1089/caff.2020.0011
David N Ruskin ₁ , Masahito Kawamura ₂ , Susan A Masino ₁

Affiliation

众所周知，神经调节剂腺苷通过腺苷 A1 受体亚型起作用，可以限制或阻止癫痫发作。2008 年，腺苷被提议作为生酮饮食 (KD) 抗惊厥机制的关键成分，KD 是一种非常低碳水化合物的饮食，对药物难治性癫痫非常有效。在这项研究中，我们回顾了有关腺苷、酮症和抗惊厥/抗癫痫作用之间交叉点的累积数据。在癫痫和癫痫发作的几种啮齿动物模型中，通过使用腺苷 A1 受体拮抗剂可以逆转生酮治疗（KD 本身、外源性酮体、中链甘油三酯或脂肪酸）的抗癫痫作用。此外，KD 治疗会提高大脑中的细胞外腺苷和组织腺苷含量。在脑切片中维持或模拟生酮环境的努力揭示了由基于突触前和突触后腺苷 A1 受体的效应产生的兴奋性降低的状态。长期癫痫发作减少可能是由于基于腺苷的表观遗传效应。总之，有越来越多的证据表明在生酮状态下腺苷能抗惊厥作用。在某些情况下，主要触发因素是大脑中的葡萄糖轻度但持续降低。需要更多的研究来调查腺苷在这些治疗的抗癫痫和神经保护作用中的重要性。未来的研究可能会开始研究替代的腺苷促进策略，以增强 KD 或自行寻找治疗用途。

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Adenosine and Ketogenic Treatments.

It is well known that the neuromodulator adenosine, acting through the adenosine A1 receptor subtype, can limit or stop seizures. In 2008, adenosine was proposed as a key component of the anticonvulsant mechanism of the ketogenic diet (KD), a very low carbohydrate diet that can be highly effective in drug-refractory epilepsy. In this study, we review the accumulated data on the intersection among adenosine, ketosis, and anticonvulsant/antiepileptogenic effects. In several rodent models of epilepsy and seizures, antiseizure effects of ketogenic treatments (the KD itself, exogenous ketone bodies, medium-chain triglycerides or fatty acids) are reversed by administration of an adenosine A1 receptor antagonist. In addition, KD treatment elevates extracellular adenosine and tissue adenosine content in brain. Efforts to maintain or mimic a ketogenic milieu in brain slices reveal a state of reduced excitability produced by pre- and postsynaptic adenosine A1 receptor-based effects. Long-lasting seizure reduction may be due to adenosine-based epigenetic effects. In conclusion, there is accumulating evidence for an adenosinergic anticonvulsant action in the ketogenic state. In some cases, the main trigger is mildly but consistently lowered glucose in the brain. More research is needed to investigate the importance of adenosine in the antiepileptogenic and neuroprotective effects of these treatments. Future research may begin to investigate alternative adenosine-promoting strategies to enhance the KD or to find use as treatments themselves.

更新日期：2020-09-16

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