Neocortical and hippocampal changes after multiple pilocarpine-induced status epilepticus in rats.

Abstract

PURPOSE: Multiple episodes of pilocarpine-induced status epilepticus (SE) in developing rats (P7-P9) lead to progressive epileptiform activity and severe cognitive impairment in adulthood. The present work studied possible underlying abnormalities in the neocortex and hippocampus of pilocarpine-treated animals. METHODS: Wistar rats were submitted to pilocarpine-induced SE at P7, P8, and P9, and were killed at P35. Immunocytochemistry was performed on 50-microm vibratome sections, by using antibodies against nonphosphorylated neurofilament (SMI-311), parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase (GAD-65). Ten-micron cryostat sections were processed for immunohistoblot by using antibodies against GluR1, GluR2/3, and GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits and NR2ab N-methyl-D-aspartate (NMDA) receptor subunit. RESULTS: Adult rats submitted to SE at P7-9 showed: (a) altered distribution of neocortical interneurons; (b) increased cortical and reduced hippocampal GAD-65 expression; and (c) altered expression of hippocampal AMPA and NMDA receptors. CONCLUSIONS: We conclude that multiple SE episodes during P7-9 generate long-lasting disturbances that underlie behavioral and electrographic abnormalities later in life.