Abstracts

Rationale: Cell-mediated inflammation contributes to status epilepticus (SE)-induced neuronal injury in the adult brain, but its role in the immature brain has not been fully characterized. The goal of this study was to determine the time course of leukocyte infiltration and microglial activation in our lithium-pilocarpine model of SE in fourteen-days-old (P14) rat pups. Methods: Rat pups were given 3 mEq/kg lithium chloride i.p. on the day before the induction of SE, which was carried out at P14 by subcutaneous injection of 60 mg/kg pilocarpine hydrochloride. Control animals were given an equal volume of saline subcutaneously. Presence of macrophages/activated microglial cells, T cells and granulocytes in the brain was determined semi-quantitatively by immunohistochemical methods 6 h to 1 week following SE and correlated to the appearance of neuronal injury detected by fluoro-jade B staining. Results: Neuronal injury was observed in the CA1 pyramidal layer, the dentate gyrus inner granule cell layer and the mediodorsal thalamic nucleus 24 h to 7 days after SE onset. Microglial activation and/or macrophage accumulation was detected in the whole hippocampal formation (mainly CA1 pyramidal cell layer, stratum radiatum and lacunosum-moleculare and dentate gyrus), and in the mediodorsal thalamus 24 h, 72 h and 1 week following SE. In the retrosplenial cortex, devoid of fluoro-jade B staining, macrophages/microglial cells were observed only 24 h following SE. SE induced a massive T cell infiltration at 24 h after SE onset in the whole hippocampal formation (mainly CA1 pyramidal cell layer, stratum radiatum and lacunosum-moleculare and dentate gyrus) and the mediodorsal thalamus. Infiltration in the hippocampal formation was still visible 72 h following SE and disappeared by 1 week. Infiltration of T cells into the retrosplenial cortex was mild and only visible 24 h following SE. SE induced a mild and transitory granulocytic infiltration limited to the hippocampal formation 24 h after SE onset. The results are summarized in table 1. Conclusions: These data demonstrate that SE in the immature brain can induce a massive cellular inflammatory response associated with neuronal injury.