Norepinephrine is required for the anticonvulsant effect of the ketogenic diet
Norepinephrine is required for the anticonvulsant effect of the ketogenic diet
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DOI：
10.1016/s0165-3806(01)00213-9
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发表时间：
2001-08-23
期刊：
影响因子：
--
通讯作者：
Schwartzkroin, PA
中科院分区：
文献类型：
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作者：
Szot, P;Weinshenker, D;Schwartzkroin, PA
生酮饮食(KD)是一种高脂肪、低碳水化合物的饮食，用于治疗常规抗癫痫药物(AEDs)无效的癫痫儿童。KD的抗惊厥机制尚不清楚。为了确定去甲肾上腺素系统是否在KD的抗惊厥作用中起中介作用，给缺乏去甲肾上腺素(NE)和去甲肾上腺素(NE)含量正常的DBH+/-的多巴胺β-羟化酶基因敲除(DBH-/-)小鼠喂食标准的啮齿动物饲料或KD。与饲喂正常饲料的DBH+/-小鼠相比，给予KD的DBH+/-小鼠暴露于惊厥剂氟乙醚后，出现肌阵挛(MJ)和全身性阵挛-强直(CT)发作的潜伏期显著延长。相比之下，喂食KD的DBH小鼠对MJ和CT的惊厥潜伏期与喂食正常食物的DBH-/-小鼠相当。这些结果表明，KD需要一个完整的、功能正常的去甲肾上腺素能神经系统才能发挥抗惊厥作用。爱思唯尔科学公司出版。
Ketogenic diet (KD) is a high fat, low carbohydrate diet used to treat children with epilepsy that are refractory to conventional antiepileptic drugs (AEDs). The anticonvulsant mechanism of the KD is unknown. To determine if the noradrenergic system has a role in mediating the anticonvulsant action of the KD, dopamine beta -hydroxylase knockout (Dbh -/-) mice that lack norepinephrine (NE) and Dbh +/- littermates that have normal NE content were fed either a standard rodent chow or the KD. When exposed to the convulsant flurothyl, Dbh +/- mice fed the KD had significantly longer latencies to myoclonic jerk (MJ) and generalized clonic-tonic (CT) seizures than Dbh +/- mice fed normal chow. In contrast, Dbh mice fed the KD had seizure latencies to both MJ and CT comparable to Dbh -/- mice fed normal chow. These results suggest that an intact, functional noradrenergic nervous system is required for the KD to exert an anticonvulsant effect. Published by Elsevier Science B.V.