Hori A, Tandon P, Holmes G L, Stafstrom C E
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Epilepsia. 1997 Jul;38(7):750-8. doi: 10.1111/j.1528-1157.1997.tb01461.x.
Despite use of the ketogenic diet (KD) for >75 years its effectiveness or mechanism of action has been examined in few animal studies. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in adult rats.
Rats fully kindled from the amygdala were divided into KD-fed or standard rat diet-fed groups; diet treatment continued for 5 weeks. The KD approximated at 4:1 ("classic") ketogenic diet and consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was contributed by fat and 8% was contributed by protein. Afterdischarge threshold and duration (ADT, ADD) and stage 5 seizure threshold and duration (ST, SD) were assessed weekly for 5 weeks. During week 3, learning and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test.
Rats receiving the KD became ketonemic and had weight gains similar to those of control rats. As compared with rats receiving a standard diet, those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard to ADD or SD at any time during the study, and both groups performed similarly in the water maze and open field test.
In the kindling model, the KD afforded transient protection against the focal generation of kindled seizures but not seizure spread. Rats that received the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promising model for study of the anticonvulsant mechanisms of ketosis.
尽管生酮饮食（KD）已使用超过75年，但在少数动物研究中对其有效性或作用机制进行了研究。我们使用癫痫点燃模型，测试了成年大鼠实验性生酮饮食的抗惊厥有效性和行为后果。
从杏仁核完全点燃的大鼠分为生酮饮食喂养组或标准大鼠饮食喂养组；饮食治疗持续5周。生酮饮食近似于4:1（“经典”）生酮饮食，由（按重量计）70%脂肪、14%蛋白质、无碳水化合物以及适量维生素、矿物质和纤维组成；提供的能量92%由脂肪贡献，8%由蛋白质贡献。每周评估5周的后放电阈值和持续时间（ADT，ADD）以及5期癫痫发作阈值和持续时间（ST，SD）。在第3周，通过水迷宫测试学习和记忆，并通过旷场试验评估对新环境的行为反应。
接受生酮饮食的大鼠出现酮血症，体重增加与对照大鼠相似。与接受标准饮食的大鼠相比，接受生酮饮食的大鼠在治疗的前2周ADT和ST升高。在研究期间的任何时候，对照组和生酮饮食喂养组在ADD或SD方面没有差异，并且两组在水迷宫和旷场试验中的表现相似。
在点燃模型中，生酮饮食提供了针对点燃性癫痫发作灶性产生的短暂保护，但对癫痫发作传播无效。接受生酮饮食的大鼠在空间学习或探索行为任务上与对照喂养的大鼠表现没有差异。我们的结果为研究酮症的抗惊厥机制提供了一个有前景的模型。
