Pilocarpine으로 유발된 간질중첩증에서 케톤생성 식이요법의 해마세포 손상 방어에 관한 연구

Protective Effect of Ketogenic Diet on the Hippocmpal Damage Produced by Pilocarpine-induced Status Epilepticus in Rats

1) KD는 pilocarpine에 의하여 유발되는 간질중첩증의 발현, 경련의 정도, 자발적인 완화에 영향을 미치지 않았다. 2) 3주간의 KD 식이는 충분한 정도의 케톤증을 유발하였다. 3) 3주간의 KD 식이는 흰쥐의 간질중첩증 2주 후에 시행된 병리학적 검사에서 H-E 염색 및 C-V 염색에서 RD를 식이한 흰쥐에 비하여 세포사가 현저히 적었으며 이러한 차이는 CA3, 치상회, CA1의 순서로 뚜렷하였다. 4) KD 식이는 Timm 과립의 형성을 억제하였으며 이는 특히 간질중첩증 유발 이전에 시행된 KD 식이에 의하여만 억제되었다. 즉, 3주간의 KD 식이 후 간질중첩증을 유발한 이후에 RD 식이로 변환한 경우나 간질중첩증 전후 모두 KD를 시행한 경우는 Timm 과립의 형성이 뚜렷이 억제되었으나, 3주간의 RD 식이 후 간질중첩증을 유발한 다음 KD로 식이를 변환하거나 RD를 유지한 경우는 Timm 과립의 형성이 뚜렷하였다. 이상의 결과로 KD는 간질중첩증으로 인한 세포사를 억제할 뿐만 아니라 그 이후에 나타나는 간질형성기전을 억제하는 효과가 있는 것으로 판단되었다.

Purpose : Although ketogenic diet(KD) is an old method of treating epilepsies, its outstanding antiepileptic effect in some epileptic patients need re-evaluation. This study was performed to evaluate the anti-epiletogenic effect of KD. Methods : In the preliminary experiment, to select a proper animal model of status epilepticus(SE), an evaluation of EEG and behavioral characteristics of pilocarpine-induced SE model was done in 12 Sprague-Dawley rats. As the aim of the first experiment was to evaluate neuronal death in the hippocampus of similarly convulsed rats, the 10-20 mg/kg of diazepam ip. injection was given to cease SE in each stage of SE in KD and regular diet(RD) rats. Previous diet was maintained for two weeks until the evaluation of pathological changes with H-E and C-V stainings(64 rats, second experiments). In order to investigate whether the differences in the neuronal damage cause different mossy fiber sprouting or not, 40 rats were fed with KD and RD(20 rats each) 4 hours before pilocarpine-induced SE. After the treatment of SE with diazepam, half of previous KD rats maintained with KD and remaining 10 rats were fed with RD. Also previous RD rats were fed with RD and KD in the same way. Mossy fiber sprouting and synaptic reorganization was determined by Timm's staining 4 weeks after SE. Results : Pilocarpine-induced SE showed reliable EEG and behavioral patterns in all rats. Also, KD did not have any influence on SE induced by pilocarpine in terms of SE induction time and severity. Neuronal damages in CA1, CA3, and dentate gyrus were less prominent in the KD rats in every SE stage. Rats with RD before their SE showed significant Timm's(+) bands, whereas rats with KD after the SE did not show any differences. Conclusion : KD consistently protect neuronal damage caused by seizures in the hipocampus. this neuroprotection causes less mossy fiber synaptic reorganization.