Abstracts

Rationale: The ketogenic diet (KD) was designed to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies: acetoacetate (ACA), beta-hydroxybutyrate (BHB), and acetone. Recent research data suggest that the anticonvulsant efficacy of the KD may be due in part to the direct actions of ketone bodies. This study was designed to investigate the effects of BHB on pilocarpine-induced seizures in mice. Methods: Eighty-two male ICR mice at postnatal day 49 were used. All mice were pretreated with scopolamine methylbromide (1mg/kg) 30 min prior to pilocarpine injection. Experimental mice (n = 42) were injected intraperitoneally with BHB (20 mmol/kg) 15 min prior to pilocarpine administration, while control animals (n = 40) with normal saline. And then pilocarpine (300 mg/kg) was administered intraperioneally. Mice were monitored for 2 h after pilocarpine injection, and seizure behavior grades were evaluated by Racine’s scale. Results: All mice developed typical seizure behaviors. The mean (± SD) seizure onset time was significantly prolonged in the BHB-treated mice compared with the controls (4.8 ± 1.9 min vs. 3.7 ± 1.9 min, p<0.01). Conclusions: This study demonstrates that BHB increases pilocarpine-induced seizure threshold in mice. This finding suggests that BHB may be directly anticonvulsant.