Xu Xiang-ping, Sun Ruo-peng, Jin Rui-feng
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China.
Zhonghua Er Ke Za Zhi. 2006 Feb;44(2):100-4.
Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus.
Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus.
KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same.
Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.
生酮饮食（KD）是一种高脂肪、低蛋白、低碳水化合物的饮食。其抗癫痫作用是肯定的，但潜在机制尚不清楚。本研究旨在从海马突触重组和GluR(5)表达的角度揭示可能的机制。
在出生后第28天用 kainic 酸诱导 Sprague-Dawley 大鼠癫痫发作，所有对照动物喂食正常啮齿动物饲料，而实验大鼠喂食生酮饲料8周。记录自发复发性癫痫发作。通过 Timm 染色和 Nissl 染色研究海马中的苔藓纤维发芽和神经元损伤。应用 Western blot 和 RT-PCR 方法检测海马中 GluR(5)和 GluR(5) mRNA 的表达。
喂食 KD 的大鼠（1.40±1.03）自发复发性癫痫发作明显少于喂食对照饮食的大鼠（7.36±3.75）。在 KA 诱导的动物中，齿状回内分子层苔藓纤维发芽的平均 A 值明显高于生理盐水对照动物，但在不同饮食喂养组中相似。在 CA(3)区的 Timm 染色平均 A 值以及海马回、CA(3)和 CA(1)区神经元的 Nissl 染色中未发现显著差异。KA 点燃后，喂食 KD 的动物海马中 GluR(5)表达[(189.38±40.03)/mg pro]明显高于喂食对照饮食的动物[(128.79±46.51)/mg pro]，尽管它们的 GluR(5) mRNA 相同。
苔藓纤维发芽可能是 KA 诱导模型中癫痫发生的原因，KD 可以抑制这些动物的癫痫发作。KD 可能上调幼鼠 CA(1)抑制性中间神经元中的 GluR(5)，从而导致抑制作用增强以防止癫痫发作的传播。
