An anticonvulsant profile of the ketogenic diet in the rat
An anticonvulsant profile of the ketogenic diet in the rat
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DOI：
10.1016/s0920-1211(02)00086-4
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发表时间：
2002-08-01
影响因子：
2.2
通讯作者：
Eagles, DA
中科院分区：
文献类型：
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作者：
Bough, KJ;Gudi, K;Eagles, DA
本研究旨在评价高脂生酮饮食(KD)对大鼠的抗惊厥作用。动物饲喂四种实验饲料：(1)卡路里限制酮(KCR)，(2)卡路里限制正常(NCR)：(3)临时性生酮(KAL)或(4)临时性正常(NAL)。限制卡路里的饮食是按卡路里相等的数量喂食的。所有动物在P37岁时开始饮食治疗，每只动物都接受五种化学诱导癫痫试验中的一种：荷包牡丹碱(BIC：S.C.)。印防己毒素(PICA，S.C.)。Kainate(Ka，I.P.或S.C.)和γ-丁内酯(GBL，I.P.)。士的宁(S.C.)。在氯胺酮/赛拉津麻醉下植入双极硬膜外电极，记录失神发作时脑电的棘波放电(SWD)特征。在每次实验中，在致痫前，用分光光度法测定血中β-羟丁酸盐(BHB)的水平，以测定酮血症。与对照组相比，饲喂生酮饮食(即限制卡路里或随意进食)的动物血液中的BHb水平更高。癫痫发作结果显示，KD治疗：(1)减少荷包牡丹碱诱导的惊厥发生率，(2)减少印防己毒素诱导的癫痫发作次数(仅限KCR组)；(3)延长GBL诱导的SWD的潜伏期，缩短SWD的次数和持续时间，但(4)对士的宁诱导的癫痫发作没有保护作用；(5)使KA诱导的癫痫发作更加严重。综上所述，这些结果表明KD对大鼠具有抗惊厥作用，包括由GABA受体(BIC、PIC、GBL)诱导的阈值惊厥，而不是由甘氨酸(士的宁)或Ka亚类谷氨酸受体诱导的惊厥。独一无二的是，KD是唯一一种既能预防大鼠惊厥发作，又能预防非惊厥(失神)发作的治疗方法。(C)2002 Elsevier Science B.V.保留所有权利。
The present study was designed to evaluate the anticonvulsant effects of a high-fat ketogenic diet (KD) in rats. Animals were maintained on one of four experimental diets: (1) calorie-restricted ketogenic (KCR), (2) calorie-restricted normal (NCR): (3) ad libitum ketogenic (KAL) or (4) ad libitum normal (NAL). The calorie-restricted diets were fed in quantities such that they were calorically equivalent. All animals began diet treatment at age P37 and each was subjected to one of five chemically-induced seizure tests: bicuculline (BIC: s.c.). picrotoxin (PICA, s.c.). kainate (KA, i.p. or s.c.) and gamma-butyrolactone (GBL, i.p.). strychnine (s.c.). Bipolar epidural electrodes were implanted under ketamine/xylazine anesthesia to permit recording the spike and wave discharges (SWD) characteristic of electroencephalograms during absence seizures. Ketonemia was assayed by measuring blood levels of beta-hydroxybutyrate (BHB) spectrophotometrically prior to induction of seizures in each experiment. Animals fed ketogenic diets (i.e. either calorie restricted or ad libitum) exhibited greater blood levels of BHB compared to control groups. Seizure results show that treatment with a KD: (1) reduced the incidence of bicuculline-induced convulsions, (2) diminished the number of picrotoxin-induced seizures (KCR group only); (3) increased latency to GBL-induced SWD and reduced both the number and duration of SWD but (4) conferred no protection from strychnine-induced seizures, and (5) made KA-induced seizures more severe. Together these results indicate a spectrum of anticonvulsant action for the KD in rats that includes threshold seizures induced via GABA receptors (BIC, PIC, GBL) but not those induced at glycine (strychnine) or the KA-subclass of glutamate receptors. Uniquely, the KD is the only treatment described that protects against both convulsive and non-convulsive (absence) seizures in rats. (C) 2002 Elsevier Science B.V. All rights reserved.