Flurothyl-유발 발작 감수성에 대한 케톤생성 식이요법의 효과

Abstract

Purpose：Despite decades of clinical experience with the ketogenic diet (KD), its efficacy and mechanisms of action have been examined in few animal studies. The present study was designed to investigate the effect of a KD on flurothyl-induced seizure susceptibility in rats. Methods：Twenty male Sprague-Dawley rats were divided into two equal groups. Dietary treatment was initiated at P39. The experimental group was fasted for a day and then fed a KD consisting of [fat]：[protein + carbohydrate] ratio of 4.3：1, while the control group was fed a standard rodent chow. On treatment day 21, blood β-hydroxybutyrate (BHB) levels were assayed and seizures were chemically induced by flurothyl (40 μl/min). Seizure susceptibility was defined as the latency from the start of flurothyl infusion to the onset of a generalized seizure (loss of posture with bilateral hindlimb tonic extension). Shorter latencies reflect greater seizure susceptibility. Results：Blood BHB levels in the KDtreated group were significantly higher than those of the control group (4.75±0.38 [n=10] vs. 0.19±0.02 [n=10] mM, respectively；p<0.01). The latencies to the onset of a generalized seizure were 673.2±32.95 [n=10] and 523.0±31.11 [n=10] seconds for the KD-treated and control groups, respectively (p<0.01). Conclusion：This study demonstrates the significant decrease in the susceptibility of flurothyl-induced seizure in the KD-treated rats. Furthermore, we have established a working animal model from which future mechanistic studies can be based.