Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats.
OBJECTIVE
The aim of the present study was to observe possible cortical abnormalities after repetitive pilocarpine-induced status epilepticus (SE) in rats during development.


METHODS
Wistar rats received intraperitoneal injection of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35, and immunocytochemistry procedures were 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). Selected sections were used for the TUNEL method and double-labeling experiments, with different mixtures of the same markers.


RESULTS
The major findings of the present work were (a) altered intracortical circuitry development; (b) anticipation of PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic process.


CONCLUSIONS
From these results, we suggest that previously healthy brain, without genetic abnormalities, might develop an "acquired" disruption of cortical development whose evolution reproduces some characteristics of the childhood epilepsies associated with cognitive impairment.
da Silva
Alexandre Valotta
AV
Universidade Federal de São Paulo, São Paulo, Brazil. valotta.nexp@epm.br
Regondi
Maria Cristina
MC
Cavalheiro
Esper Abrão
EA
Spreafico
Roberto
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000187:drug effects* / Q000254:growth & development; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009421:Nervous System Malformations / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D010862:Pilocarpine / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
D010862:Pilocarpine; D005968:Glutamate Decarboxylase