Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats

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Silva, Alexandre Valotta da [UNIFESP]
Regondi, T. C.
Cavalheiro, Esper Abrão [UNIFESP]
Spreafico, Roberto
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Purpose: 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-mu m vibratome sections, by using antibodies against nonphosphorylated neurofilament(SMI-311), parvalburnin (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. Key Words: Immature brain-Early insult-Apoptosis-Neocortex-Interneurons.
Epilepsia. Oxford: Blackwell Publishing, v. 46, p. 22-30, 2005.