Susceptibility to Kindling in the Rat Model of In Utero Radiation-Induced Cortical Dysplasia and Epilepsy
Abstract number :
3.007
Submission category :
Year :
2001
Submission ID :
634
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
T. Kunieda, M.D., Neurology, Cleveland Clinic Foundation, Cleveland, OH; I.M. Najm, M.D., Neurology, Cleveland Clinic Foundation, Cleveland, OH; S. Kondo, M.D., Neurosurgery, Tottori University, Yonago, Tottori, Japan; A. Boongird, M.D., Neurology, Clevel
RATIONALE: In utero radiation-induced epilepsy model in rats mimics the histological features of cortical dysplasia seen in humans. We previously reported on the occurrence of spontaneous seizures in the same animal model. In this study, we compared the susceptibility to the development of kindling in control rats (non-treated) and rats treated in utero with various doses of radiation.
METHODS: The litters of time-pregnant Sprague-Dawley rats, which were exposed to whole body radiation on embryonic day 17, were included in this study. Pregnant rats were subjected to 3 radiation doses (100, 145, and 175 cGy). Moreover, the offspring of non-radiated pregnant rats were used as age-matched controls. At postnatal day 60, stereotaxic electrode implantations were carried out. For the purpose of EEG recording, screw electrodes were placed in the skull over bilateral frontal cortex and a twisted-pair monopolar electrode was inserted into the left hippocampus. A bipolar depth electrode was inserted symmetrically into the right hippocampus for stimulation. The electrical stimulations with minimal intensity, which evoked afterdischarge (AD), were delivered twice a day. Convulsive responses were scored according to Racine's five-stage paradigm for limbic seizures. We analyzed AD duration and the number of stimulations necessary for 5 consecutive stage-V seizures (fully kindled state) in each group. At the end of the kindling procedure, the rats were sacrificed and their brains were stained with Cresyl-Violet for histological examinations.
RESULTS: While the mean of AD duration evoked by the last 5 stimulations showed no difference among the 4 treatment groups, the total number of stimulations for fully kindled state was significantly smaller in 145 and 175cGy group, as compared to normal rats. Histological studies showed neuronal dispersion especially in CA1-CA3 sub-fields only in the radiated group. The severity of the pathological changes in the cortex and hippocampus were radiation-dependent. Moreover, in 175cGy group, the absence of corpus callosum was constantly identified.
CONCLUSIONS: This study shows that in utero radiation-induced cortical dysplasia is associated with a susceptibility to epileptogenicity. This susceptibility is correlated with the severity of neocortical and hippocampal histological abnormalities.
Support: 2000 Research Grant Recipients by National Epifellow Foundation