Anticonvulsant Effects of β-Hydroxybutyrate in Mice

BACKGROUND AND PURPOSE The ketogenic diet was formulated to mimic the biochemical changes seen upon fasting, specifically the formation of ketone bodies. 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 anticonvulsant effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in mature mice. METHODS Eighty-two male ICR mice at postnatal day 49 were used. All mice were pretreated with scopolamine methylbromide 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. Pilocarpine (300 mg/kg) was administered intraperitoneally and mice were monitored for 2 h after pilocarpine injection. RESULTS All mice developed typical seizure behaviors. The mean (±SD) latency to the onset of seizures was significantly prolonged in the BHB-treated mice compared with controls (4.83±1.95 min vs. 3.67±1.90 min, p<0.01). CONCLUSIONS This study demonstrates that treatment with BHB prolongs the latency to the onset of seizures induced by pilocarpine in mature mice and suggests that BHB, one of the ketone bodies, may have direct anticonvulsant effects.