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

Epilepsia. 2005:46 Suppl 5:22-30. doi: 10.1111/j.1528-1167.2005.01003.x.

Abstract

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cerebral Cortex / abnormalities*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / growth & development
  • Glutamate Decarboxylase / metabolism
  • Immunohistochemistry
  • In Situ Nick-End Labeling / methods
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Male
  • Nervous System Malformations / chemically induced
  • Nervous System Malformations / metabolism
  • Nervous System Malformations / physiopathology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Pilocarpine / adverse effects*
  • Pilocarpine / pharmacology
  • Rats
  • Rats, Wistar
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / metabolism
  • Status Epilepticus / physiopathology

Substances

  • Pilocarpine
  • Glutamate Decarboxylase