Abstracts

Lithium pilocarpine status epilepticus (LiPC-SE) causes prolonged seizures and subsequent widespread neuronal injury. In the developing rat brain, untreated LiPC-SE results in age dependent hippocampal injury as well as widespread extrahippocampal neuronal damage. We examined whether brief durations of SE are sufficient to induce injury in the immature brain., EEG data was collected using acquisition software obtained from wireless transponders implanted s.c. in two week old wistar pups. Rats were pretreated with LiCl (3 mEq) on the day of surgery and then subjected to SE 16-20 hr later with pilocarpine (60 mg/kg) at P14. Diazepam(5 mg/kg) and phenobarbital (25 mg/kg) were given after varying durations of SE using EEG recordings to determine both the delay of onset after PC injection, as well as the total duration of SE. 24 hr after the onset, rats were given pentobarbital (100 mg/kg) followed by perfusion/fixation with 4% paraformaldehyde. Brains were embedded in paraffin and cut at 8 [mu] intervals. Sections were stained with Fluoro-Jade B (F-J B) as a marker of neuronal injury, and analyzed using a semiquantative scale ( 0 = no injury, 1 = trace, 2 = [lt] 10%, 3 = 10-25%, 4 = 26-50%, 5 = [gt] 50% F-J B labeled neurons) bilaterally in three sections containing the dorsal hippocampus., SE was established in over 90% of the P14 rats. Behavioral manifestations of seizures appeared almost immediately after PC injection, but synchronized video monitoring revealed a delay of 9.8 [plusmn] 1.6 min before the appearance of continuous, rhythmic, high frequency electrographic activity used to mark the onset of SE. Prolonged recordings showed that the combination of diazepam/phenobarbital was sufficient to prevent the return of seizures over the following 24 hr period. While 30 min of SE was not sufficient to induce hippocampal injury with the exception of trace dentate granule cells, injury was seen in the amygdala (2.3 [plusmn] 0.1) and cortex (1.8 [plusmn] 0.1). No brightly labeled neurons were seen in the thalamus, but some lightly stained, irregularly shaped neurons were detected., Previous studies have shown that P14 rats subjected to LiPC experience several hours of SE resulting in extensive neuronal injury, particularly in the CA1 hippocampal subfield. While early pharmacological intervention was sufficient to protect those neurons from injury, extrahippocampal structures remain vulnerable after only 30 min of SE. Studies in adult rats suggest protection of the Ammon[apos]s horn alone is not sufficient to prevent epilepsy. 25% of untreated P14 rats undergoing LiPC-SE go on to demonstrate spontaneous seizures. Whether the neuronal injury that results after only 30 min is sufficient to induce epilepsy is under investigation., (Supported by NS046516 [amp] DAPA Foundation (RS), AEAC Association (SA).)