Abstracts

Status epilepticus (SE) is a neurological emergency and a common problem in neonates. To date, effective treatments to stop ongoing status epilepticus in this age group have not been identified. To assess efficacy and morbidity from the treatment of prolonged seizures in the immature brain, it is necessary to develop screening assays., SE was induced in postnatal day 15(P15) and 21(P21) rats by systemic administration of kainic acid (KA) 3.5mg/kg (P15) and 10mg/kg (P21) or lithium-pilocarpine (PI) 60mg/kg (P15) and 30mg/kg (P30). Rats were monitored by EEG with an electrode in the CA1 region of the hippocampus. In both models behavioral seizures continue for several hours and electrographic seizures continue for more than 24 hours if left untreated. After one hour of electroclinical SE, rats were treated with pentobarbital (PB), diazepam (DZ), or saline. Rats were then intermittently monitored for cessation of behavioral and electrographic seizures, and for mortality for 3 days following treatment to confirm that the seizures stopped and did not recur., Both drugs can stop the ongoing seizures both behaviorally and electrographically. PB (50mg/kg) was XX% effective in stopping KA and PI induced SE in both P15 and P21 rats. DZ (20mg/kg) was effective in stopping SE in 50-64% of rats in 3 of the 4 groups. In the KA P21 group, it was not effective. Higher doses of diazepam did not improve the outcome in P15 pups in KA-SE. When effective, DZ stopped SE much quicker than PB (p[lt].0001). In most groups, mortality from SE did not change irrespective of whether SE was stopped or not. In the P15 PI group, treatment with either drug had increased mortality compared to untreated SE., This study shows that it is possible to abort seizures in the developing rat even after 1 hour of SE using drugs at appropriate doses. The drugs, when effective, stop both the behavioral and the EEG seizures. The action of DZ is rapid, suggesting that subsequent treatments can be quickly initiated if SE does not stop within 1-2 minutes. On the other hand, PB takes significantly longer to work, and more time is needed to determine if the therapy will stop the seizures. Age and cause of SE may contribute to drug-induced morbidity. Our protocol can be used to assess the efficacy and morbidity of new agents., (Supported by NIH NINDS grants K12-NS048856 (NSADA) (HH) and R01-NS20253 (SLM).)