Abstracts

Prolonged febrile seizures and status epilepticus (SE) have been implicated as predisposing factors for temporal lobe epilepsy and/or hippocampal sclerosis. Inflammatory responses have been shown to have long term consequences on the developing brain following kainic acid. We have previously shown an age specific pattern of neuronal injury following lithium-pilocarpine (LiPC) induced SE. Here, we assess the contribution of varying degrees of inflammation in the immature rat brain. Rats were pretreated 16-20hr with 3mEq LiCl (i.p.), followed by 60mg/kg PC (s.c.) to induce SE at postnatal day 14 (P14). In order to induce an inflammatory response, lipopolysaccharide (LPS) was injected i.p. at 10[mu]g/kg or 50[mu]g/kg, two hours prior to the induction of seizures. Rats were monitored for behavioural onset of SE and only those that reached at least stage 3 (modified Racine scale) were included. Four doses of LPS were studied: SE with saline injection (SE), SE+LPS 10[mu]g/kg (SE+LPS10), SE+LPS 50[mu]g/kg (SE+LPS50), and SE+LPS 250[mu]g/kg (SE+LPS250). Rats were killed 24hr after the start of SE, and their brains cut at 8 microns for cell counts using H[amp]E as a marker of neuronal injury in the hippocampus. There was zero mortality in all groups except in SE+LPS250 (2/5). The number of eosinophilic neurons in CA1 was related to the dose of LPS. SE resulted in 55.7[plusmn]12.9 vs 82.3[plusmn]11.7 in SE+LPS10, and was significantly increased in SE+LPS50 (122.4[plusmn]19.6; p [lt] 0.05). No differences in counts were observed among the groups in CA3, hilus and dentate granule cells. We have previously demonstrated that prolonged LiPC SE in P14 rat pups does not result in substantial hippocampal neuronal injury beyond area CA1 and that a small population of these animals go on to exhibit spontaneous seizures. Inducing an inflammatory response does not seem to exacerbate injury in those resistant regions at this age, but does worsen the neuronal population, CA1, that is vulnerable in the lithium-pilocarpine model of SE. Furthermore, the level of inflammation can contribute to the amount of neuropathological sequelae. Whether the exacerbation of this injury has long term consequences is under investigation. (Supported by AEAC Association (SA), NS046516 [amp] the DAPA Foundation (RS).)