Abstracts

Rationale: Neonatal seizures are most commonly due to hypoxic encephalopathy, and are refractory to conventional anticonvulsant drugs. To date, there are no clinically available agents that are specifically designed for parenteral use in neonatal seizures. Recently, levetiracetam (LEV) became available as a parenteral formulation. However, there is little data regarding its efficacy in preclinical neonatal seizure models.Methods: We used our previously published model of neonatal hypoxia-induced seizure to examine the efficacy of intraperitoneal LEV administration prior to exposure to hypoxia. Postnatal day 10 rat pups (n=12/group) were pretreated with vehicle (PBS), LEV 10 mg/kg, or LEV 25 mg/kg 30 min prior to global hypoxia (scaled exposure from 7-4% O₂ over 15 min). Seizure episodes were recorded by a blinded investigator, and total seizure duration during hypoxia was compared between groups using a 1 way ANOVA.Results: As previously described, vehicle treated pups experienced episodes of tonic-clonic trunk and head movements, with an average total duration of 225.7±34.8 sec. LEV treatment resulted in a significant decrease in seizure duration at 10 mg/kg (113.8±24.8 sec) and at 25 mg/kg (140.3±31.2 sec) (p<0.04).Conclusions: LEV pretreatment appears to attenuate seizure severity in the rodent model of perinatal hypoxia-induced seizures. The lower 10 mg/kg dose was slightly more effective than the 25 mg/kg, justifying evaluation of LEV doses at < 10 mg/kg in the immature rat model. The mechanism of action is unclear, including potential effects on K