Dissociation between in vitro and in vivo epileptogenicity in a rat model of cortical dysplasia.
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 Mg(2+) from the bath, epileptiform field potentials were elicited that showed a significantly higher burst integral in the freeze lesion slices compared to control slices.


CONCLUSIONS
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.
Kellinghaus
Christoph
C
Department of Neurology, The Cleveland Clinic Foundation, Ohio, USA. kelling@uni-muenster.de
Möddel
Gabriel
G
Shigeto
Hiroshi
H
Ying
Zhong
Z
Jacobsson
Berit
B
Gonzalez-Martinez
Jorge
J
Burrier
Candice
C
Janigro
Damir
D
Najm
Imad M
IM
D000818:Animals; D004195:Disease Models, Animal; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004827:Epilepsy / Q000503:physiopathology*; D005615:Freezing; D019579:Neocortex / Q000473:pathology*; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D014741:Video Recording
D010433:Pentylenetetrazole