Neocortical and Hippocampal Changes after Multiple Pilocarpine-induced Status Epilepticus in Rats


Address correspondence and reprint requests to Dr. A.V. da Silva at Lab Neurologia Experimental UNIFESP-EPM, Rua Botucatú, 862, CEP04023-900 São Paulo, SP, Brazil. E-mail:


Summary: 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-μm 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 α-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.