Effect of beta-Hydroxybutyrate on Flurothyl-Induced Seizure Susceptibility

Shin, Chang Guyn; Kim, Dong Wook

Abstract

PURPOSE
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. The present study was designed to investigate the protective effect of BHB on flurothyl-induced seizures in rats.
METHODS
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 mL/min). Seizure susceptibility was defined as the latency from the start of flurothyl infusion to the onset of a generalized seizure. Shorter latencies reflected greater seizure susceptibility.
RESULTS
The mean (+/- SEM) latency to the onset of a generalized seizure in the experimental animals treated with BHB was 476.5 +/- 13.9 seconds, which was significantly longer (P < 0.05) than the control (438.0 +/- 10.5 seconds).
CONCLUSION
This study demonstrated the significant decrease in flurothyl-induced seizure susceptibility in rats treated with BHB. Our results suggest that BHB may be directly anticonvulsant.