IN-VITRO-HYPEREXCITABILITY IN THE RAT FREEZE LESION MODEL OF CORTICAL DYSPLASIA DOES NOT TRANSLATE INTO CLINICAL EPILEPTOGENICITY
Abstract number :
2.053
Submission category :
Year :
2004
Submission ID :
4576
Source :
www.aesnet.org
Presentation date :
12/2/2004 12:00:00 AM
Published date :
Dec 1, 2004, 06:00 AM
Authors :
1,3Christoph Kellinghaus, 1,3Gabriel Moeddel, 1Hiroshi Shigeto, 1Zhong Ying, 1Berit Jacobsson, 1Candice Burrier, 2Damir Janigro, and 1Imad M. Najm
Malformations of cortical development (MCD) in humans are a frequent cause of refractory epilepsy in humans. The freeze-lesion model in rats has histopathological features similar to human polymicrogyria. Previous studies reported in-vitro hyperexcitability in this model, but in-vivo epileptogenicity has never been confirmed. A deep-freeze metal probe was applied unilaterally to Sprague-Dawley rat pups (n = 10) on P0/P1 to induce a cortical lesion. Sham-operated animals (where the probe was kept at room temperature) were used as the control group (n = 10). On P60, animals of both groups were implanted bilaterally with epidural electrodes in the frontal and parietal cortex and subsequently underwent 4 weeks of long-term video-EEG monitoring. The threshold for pentylenetetrazol (PTZ) induced seizures was determined. Afterwards, the animals were sacrificed and coronal brain sections were cresylecht violet stained for histology. In addition, epileptiform field potentials (EFP) was studied in brain slices prepared from freeze-lesioned (FL slices) and sham-operated rats (CTRL slices) in-vitro. EFP repetition rate, maximum amplitude, duration, and burst integral were compared between both groups. No interictal spikes and no electrographic or clinical seizures were found in both groups during 4 weeks of continuous EEG monitoring. The median threshold for PTZ-induced seizures was 60 mg for the lesioned group, and 45 mg for the control group. This difference was not statistically significant. No spontaneous EFP were recorded from either FL slices or CTRL slices bathed in normal artificial cerebrospinal fluid (ACSF). Upon omission of Mg2+ from the bath solution, EFP were elicited that showed a significantly higher burst integral in FL slices, compared to CTRL slices. 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 be epileptogenic in-vivo. (Supported by Innovative Medical Resarch (IMF) grants of the University of Münster/Germany to CK (KE 620201) and GM (MO 620202), National Institutes of Health (NIH) grant K08 NS02046 and 1R21 NS42354 to IN.)