Stafstrom C E, Wang C, Jensen F E
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Dev Neurosci. 1999 Nov;21(3-5):393-9. doi: 10.1159/000017389.
The electrophysiological effects of the high-fat, low-carbohydrate ketogenic diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, normal rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampal slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmission and responses to evoked stimulation, and hippocampal excitability was tested in Mg(2+)-free medium. There were no differences in EPSP slope, input/output relationship, responses to evoked stimulation or Mg(2+)-free burst frequency between slices from control and KD-fed rats. In another set of experiments, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days after KA-induced status, rats were divided into a control-fed group and a KD-fed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes than from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological parameters in normal rats. In rats made chronically epileptic by administration of KA, KD treatment was associated with fewer spontaneous seizures and reduced CA1 excitability in vitro. Therefore, at least part of the KD mechanism of action may involve long-term changes in network excitability.
使用海马切片评估高脂低碳水化合物生酮饮食（KD）对正常和癫痫（经 kainic 酸（KA）处理）成年大鼠的电生理影响。在第一组实验中，正常大鼠从出生后第 56 天（P56）开始喂食 KD 或标准对照饮食 6 - 8 周，之后处死获取海马切片。所有喂食 KD 的大鼠都出现了酮症。通过比较突触传递的细胞外测量值和对诱发刺激的反应来确定 KD 的基线效应，并在无镁培养基中测试海马兴奋性。对照大鼠和喂食 KD 的大鼠的切片在兴奋性突触后电位（EPSP）斜率、输入/输出关系、对诱发刺激的反应或无镁爆发频率方面没有差异。在另一组实验中，于 P54 通过腹腔注射 kainic 酸（KA）使大鼠癫痫发作，这导致癫痫持续状态，随后在接下来的几周内出现自发性复发性癫痫发作（SRS）。KA 诱导癫痫持续状态两天后，将大鼠分为对照喂食组和 KD 喂食组。在随后的 8 周内，喂食 KD 的动物的 SRS 明显减少。在经 KA 处理且喂食 KD 的大鼠的海马切片中，诱发的 CA1 群体峰电位比对照喂食大鼠的切片少。这些结果表明，KD 不会改变正常大鼠的基线电生理参数。在通过给予 KA 使其慢性癫痫发作的大鼠中，KD 治疗与较少的自发性癫痫发作以及体外 CA1 兴奋性降低有关。因此，KD 的作用机制至少部分可能涉及网络兴奋性的长期变化。
