Both AMPA and GABAA Receptor Changes Increase Seizure Susceptibilty in the Radiation-Induced Disorder of Cortical Development
Abstract number :
1.047
Submission category :
Year :
2000
Submission ID :
1419
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Jae-Hyoo Kim, Jung-Kil Lee, Min-Cheol Lee, Woong-Ki Chung, Myung-Kyu Kim, Young-Jong Woo, Hyung-Ihl Kim, Ha-Young Choi, Chonnam National Univ Medical Sch and Hosp, Kwangju, South Korea; Honam Medical Ctr, Kwangju, South Korea; Chonbuk National Univ, Chonj
RATIONALE: Disorders of cortical development(DCD) are the major underlying pathology of patients with medically intractable epilepsy. But, the role of NMDs on seizure susceptibility or epileptogenecity has not been documented. METHODS: We established a radiation-induced NMD in fetal Wistar rats and the lesion consistent with the human epileptogenic cortex (Neuropathol Appl Neurobiol 25(suppl 1): 70, 1999). In this study, alterations in binding to AMPA and GABAA receptors were demonstrated with quantitative in vitro receptor autoradiography by using the ligands [3H] AMPA and [3H] muscimol. Immunocytochemistry for GluR2/3 in NMD was also studied. Seizure susceptibility was tested by kainate treatment (1mg/kg, ip) and hypertermia (core body temperature > 42oC). RESULTS: Epileptic seizures, behavioral or EEG, were significantly higher in rats with NMD than in controls by the provocation of kainate or hyperthermia. In the NMD cortex, the binding to AMPA receptor was significantly increased, where as the binding to GABAA receptor was reduced. Stronger immunoreactivity to GluR2/3 was observed in dysplastic neurons than non-dysplastic neurons. CONCLUSIONS: The imbalance between excitatory and inhibitory receptors may cause the seizure susceptibility, and further develop medically intractable epilepsy.