Dissociation between in vitro and in vivo epileptogenicity in a rat model of cortical dysplasia

Christoph Kellinghaus, Gabriel Möddel, Hiroshi Shigeto, Zhong Ying, Berit Jacobsson, Jorge Gonzalez-Martinez, Candice Burrier, Damir Janigro, Imad M. Najm

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Objective. Malformations of cortical development are frequent causes of human refractory epilepsy. The freeze-lesion model in rats shows histopathological features similar to those found in human polymicrogyria. Previous studies reported in vitro hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. Methods. Neocortical freeze lesions were induced in Sprague-Dawley rat pups (n = 10) on postnatal day 0 or 1 (P0/P1). Sham-operated animals served as controls (n = 10). On P60, animals were implanted with epidural electrodes for long-term video-EEG monitoring (4 weeks). The threshold for pentylenetetrazol-induced seizures was determined. Animals were sacrificed and brain sections processed for histological staining and in vitro electrophysiological recordings. Epileptiform field potential repetition rate, amplitude and integral were compared between slices containing a cortical freeze lesion, and slices from sham-operated rats. Results. No interictal spikes and no electrographic or clinical seizures occurred in either group. The median threshold for pentylenetetrazol-induced seizures was 60 mg/kg for lesioned, and 45 mg/kg for control animals (difference not significant). No spontaneous epileptiform field potentials were recorded from either freeze-lesion or control slices bathed in normal, artificial cerebrospinal fluid (ACSF). Upon omission of Mg2+ from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices. Conclusion. Neocortical freeze lesions induced in newborn rat pups show histological characteristics reminiscent of human cortical dysplasia. Brain slices containing neocortical freeze lesions display hyperexcitability in vitro, but the same lesion does not appear to show spontaneous epileptogenicity in vivo.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalEpileptic Disorders
Issue number1
Publication statusPublished - Mar 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


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