Abstracts

Studies in adult rats have shown neuronal injury following status epilepticus (SE) for periods as brief as 20 min. High dose pilocarpine or Li-Pilocarpine (LiPC) results in SE that lasts several hours. We have previously demonstrated that LiPC-SE that is allowed to endure uninterrupted causes widespread neuronal injury in the developing rat brain and subsequent epilepsy that is a function of the age. Here, we examine the role that the duration of SE has in the immature rat brain. P14 Wistar rats were pretreated with 3mEq/kg LiCl (i.p.) 16-24 hr prior to induction of SE with pilocarpine (s.c.).The following day, rats were implanted with cortical electrodes and monitored for the onset and termination of SE. After 30 or 90 min, electrographic SE was terminated with i.p injections of diazepam (10 mg/kg) and phenobarbital (25 mg/kg). Rats were monitored overnight and perfused with 4% paraformaldehyde 24 hr after cessation of SE. Control, non-seizure animals were given AEDs following the same durations after saline injections. Brains were processed for routine histological examination for acute neuronal injury using hematoxylin/eosin or Fluoro-Jade B. Pilocarpine resulted in a rapid onset of behavioral alterations followed by cortical electrographic SE in the 2 week old rats (13.5 +/- 1.2 min). High dose diazepam/phenobarbital was effective in terminating SE (13.0 +/- 5.3 min after administration). Only scattered damage was seen after 30 min of SE. While 90 min of SE resulted in more injury to the principal cells of the hippocampus, the most extensive labeling was seen in extra-hippocampal structures, primarily the amygdala and dorsal thalamus. Previous studies in 2 week old rats revealed widespread neuronal injury when LiPC-SE was allowed to proceed without disruption. In particular, the presence of CA1 injury and the absence of hilar damage was especially prominent in these animals with 25% of the population going on to demonstrate spontaneous seizures. Here, we show that terminating SE after even 30 min greatly attenuates the subsequent injury at this developmental stage. Additionally, as SE continues for longer periods, exta-hippocampal structures suffer more extensive damage prior to that seen in the hippocampus. Whether this duration of SE and the resulting pattern of injury are sufficient to induce epilepsy is under investigation. (Supported by NS046516 (RS) and the DAPA Foundation)