β-Hydroxybutyrate increases the pilocarpine-induced seizure threshold in young mice

This study was designed to investigate the effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in young mice. Eighty-five male, postnatal day 21, ICR mice were used. All mice were pretreated with scopolamine methylbromide (1 mg/kg) 30 min prior to pilocarpine administration. Experimental mice (n = 46) were injected intraperitoneally with BHB (20 mmol/kg), 15 min prior to pilocarpine administration; control animals (n = 39) were administered normal saline. Pilocarpine (300 mg/kg) was then administered intraperitoneally to induce seizures. Mice were monitored for 2 h after pilocarpine injection, and seizure behavior grades were evaluated according to Racine’s scale. All mice developed typical seizure behaviors of grade 3 or higher. Although the severity in terms of seizure behavior grade was not significantly different between groups, the mean (± SD) latency to the onset of seizure was significantly prolonged in BHB-treated mice (5.15 ± 2.19 min) compared with controls (2.95 ± 1.06 min; p < 0.001). This study demonstrates that treatment with BHB significantly prolongs the latency to the onset of seizures induced by pilocarpine in mice and suggests that BHB, one of the ketone bodies, may be direct anticonvulsant.