Neocortical and hippocampal changes after multiple pilocarpine-induced status epilepticus in rats.
OBJECTIVE
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.
Silva
Alexandre Valotta da
AV
Universidade Federal de São Paulo, Brazil.
Regondi
Maria Cristina
MC
Cipelletti
Barbara
B
Frassoni
Carolina
C
Cavalheiro
Esper Abrão
EA
Spreafico
Roberto
R
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced* / Q000378:metabolism*
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine