| Kinetics of GABAA Receptors in An Animal Model of Irradiation-induced Neuronal Migration Disorders |
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Chan Jong Kim1, Young Jong Woo1, Min Cheol Lee2 |
1Departments of Pediatrics, Chonnam National University M edical School, Kwangju, Korea
2Departments of Pathology, Chonnam National University M edical School, Kwangju, Korea |
| 방사선 조사에 의한 신경세포 이주장애 질환 동물모델에서의 GABAA 수용체 변화 |
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김찬종1, 우영종1, 이민철2 |
1전남대학교 의과대학 소아과학교실
2전남대학교 의과대학 병리학교실 |
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| Abstract |
Purpose
: A majority of patients with neuronal migration disorders(NMDs) in cortical structures
suffer from medically intractable epilepsy. The role of NMDs on seizure susceptibility or epileptogenecity
has not been well documented. In the present study, we established an experimental
model of NMDs in Sprague-Dawley rats by exposing fetal rats to external irradiation in order to
demonstrate epileptogenic effect of NMDs lesions.
Methods
: Pregnant rats were exposed to 240cGy of external X-irradiation delivered by a linear
accelerator source on gestational day 16 and 17 to produce NMDs lesions in rat brain.
Results
: Microcephaly was evident on gross examination of the affected brains. Seizure susceptibility
was tested by a small dose of kainate(0.1mg/kg) injected intraperitoneally, and the
irradiated animals showed increased susceptibility to kainate. Histopathologic examination revealed
cortical dysplasia consisting of dyslamination of cerebral cortex and appearance of cytomegalic
neurons, neuronal heterotopia in periventricular white matter, dispersion of pyramidal layer and
hippocampal dentate gyrus, and agenesis of corpus callosum. Histopathologic change of the
cerebral cortex and hippocampus was closely correlated with seizure activity. Quantitative
autoradiography of [3H]muscimol binding to GABAA receptors was significantly reduced in NMDs
lesions(P =0.02).
Conclusion
: In utero irradiation of fetal rats resulted in histopathologic abnormalities that mimiced
several characteristic features of human neuronal migration disorders, and hyperexcitability
appears to be associated with reduction in density of GABAA receptors in the brain, particularly
in hippocampus and neocortex. |
| Key Words:
Neuronal migration disorders, GABAA receptor, Irradiation model |
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