Abstracts

RATIONALE: Neuronal migration disorders (NMDs) such as cortical dysplasia and microdysgenesis constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes in an experimentally induced NMD in rats.
METHODS: NMD lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic, and immunohistochemical findings for glutamate receptor subunit proteins (NR1, NR2A/B, GluR2, GluR3) on NMD cortex were correlated with development of behavioral seizures and EEG abnormality, which induced by kainic acid provocation. Spontaneous seizure was uncommonly occurred in NMD rats (5%), however, most of the rats developed seizures after an administration of kainic acid (90%). Prevalence, duration, and clinical stage of seizures were significantly increased in NMD rats comparing with controls.
RESULTS: Brains taken from irradiated NMD rats show microcephaly, thinning of cortex, blurring of the gray and white matter junction, and hypoplasia or agenesis of corpus callosum. Loss of lamination, neuronal heterotopia in the subpial gray and white matter, and disoriented cytomegalic neurons were noted histopathologically. Focal cortical dysplasia was identified by immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1, NR2A/B immunoreactivities on cytomegalic and heterotopic neurons in NMD rats were demonstrated.
CONCLUSIONS: The results of the present study indicate that epleptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs.
[Supported by: Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital]