Abstracts

Rationale: We recently showed that pre-existing inflammation induced by systemic administration of lipopolysaccharide (LPS) augments hippocampal neuronal injury under conditions of the lithium-pilocarpine (LiPC) model of status epilepticus (SE) in the immature rat. In the present study, we examined whether inflammation modifies the course of post-SE epileptogenesis Methods: Wistar rat pups were subjected to LiPC SE (administration of 3mEq/kg LiCl at postnatal day (P) 13 followed by the injection of pilocarpine, 60 mg/kg at P14. The study included three groups of animals: LiPC SE with saline injection 2 hr prior to, 24 and 48 hr after pilocarpine; LiPC with LPS (0.05 mg/kg) injection 2 hr prior to pilocarpine, and saline administration 24 and 48 hr after pilocarpine; LiPC with LPS injection 2 hr prior to, 24 and 48 hr after pilocarpine. Three months after the SE, the incidence of spontaneous seizures was examined using continuous one week-long video and EEG monitoring. Afterwards, animals were euthanized, and brains processed for histological evaluation using hematoxylin - eosin and flluorojade B staining, glial fibrillary acidic protein (GFAP) immunohistochemistry, and for Timm staining to reveal mossy fiber sprouting. An additional group of naïve animals was used as control for histological studies Results: After status epilepticus, spontaneous seizures were recorded in 3 out of 11 animals in SE-only group, 5 out of 8 animals in SE plus single LPS injection group, and in 4 out 8 rats in the SE plus repeated LPS injections group (p>0.05). Both the extent of neuronal cell loss in the CA1 area of the hippocampus, and the extent of mossy fiber sprouting were similar among the three groups. Furthermore, while no differences in GFAP expression were found between post-SE animals with and without spontaneous seizures, enhanced GFAP expression was observed in the animals that had received LPS injections. In 4 of 9 LPS-treated rats that developed spontaneous seizures, microglial reaction in CA1 was co-localized with fluorojade B- positive cells Conclusions: There was a trend towards enhanced epileptogenesis after SE in immature rats challenged with inflammatory provocation. Animals that were subject to SE in the presence of LPS demonstrated enhanced gliosis in the CA1