Abstracts

The ketogenic diet (KD) remains a therapy in search of explanation although it is an established treatment for patients with intractable seizures. It was designed to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies: acetoacetate (ACA), [beta]-hydroxybutyrate (BHB), and to a lesser extent, acetone. Investigators have observed that ketosis is necessary but not always sufficient for seizure control with the KD. In addition, Rho et al. (Epilepsia 2002;43:358-361.) recently reported that ACA and acetone exhibited anticonvulsant in Frings audiogenic seizure-susceptible mice. The data suggest that the anticonvulsant efficacy of the KD may be due in part to the direct actions of ACA and acetone. The present study was designed to investigate the protective effect of BHB on flurothyl-induced seizures in rats. Thirty-four male Sprague-Dawley rats were divided into two equal groups. Experimental rats (n=17) were injected intraperitoneally with BHB (20 mmol/kg), while control animals (n=17) with normal saline. Fifteen minutes later, seizures were chemically induced by flurothyl infusion (40 [mu]l/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. The mean ([plusmn] SEM) latency to the onset of a generalized seizure in the experimental animals treated with BHB was 476.5 [plusmn] 13.9 seconds, which was significantly (p [lt] 0.05) longer than the control (438.0 [plusmn] 10.5 seconds). This study demonstrates the significant decrease in flurothyl-induced seizure susceptibility in rats treated with BHB. Our results suggest that BHB may be directly anticonvulsant. (Supported by a grant of the Korea Health 21 R[amp]D Project, Ministry of Health [amp] Welfare, Republic of Korea. (02-PJ1-PG10-21301-0001))