The Effect of Topiramate on Status Epilepticus-Induced Neurotoxicity in Immature Mouse Brain.
- Author:
Sang Soo PARK
1
;
Hae Rahn BAE
;
Kyu Geun HWANG
Author Information
1. Department of Pediatrics, Dong-A University Medical School, Busan, Korea. kghyang@dau.ac.kr
- Publication Type:Original Article
- Keywords:
Topiramate;
Status epilepticus;
Neurotoxicity;
AMPA glutamate receptor;
GABA receptor
- MeSH:
Animals;
Brain*;
Butyric Acid;
Glutamic Acid;
Hippocampus;
Mice*;
Microscopy, Confocal;
Neurons;
Receptors, GABA;
Status Epilepticus;
Up-Regulation
- From:
Journal of the Korean Child Neurology Society
2006;14(2):193-206
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE:This study was performed to elucidate that status epilepticus (SE) induces long- term neuronal damages in an immature brain and to evaluate that topiramate (TPM) has a protective effect. METHODS:We investigated the changes in a subtype expression of glutamate and gamma- amino butyric acid (GABA) receptors, and the structural integrity due to cell losses in the mouse pup hippocampus after SE using an immunoblot and confocal microscopy. RESULTS:SE induced significant cell losses with structural changes in the hippocampus 1 month later. SE up-regulated the glutamate receptor1 (GluR1) expression with an increased ratio of GluR1 to glutamate recptor2 (GluR2), leading to the formation of Ca2+ permeable alpha- amino-3-hydroxy-5-methyl-4-isoxazoleepropionic acid (AMPA) receptors for the enhanced neurotoxicity. TPM prevented the SE-induced GluR1 expression. The expression of GABAA receptors was highly increased 1 month after SE, whereas that of GABAB receptors was not changed. The TPM treatment attenuated SE-induced upregulation of GABAA receptors. SE induced significant cell losses and disruption of structural integrity in the hippocampus CA1 and CA3 regions, but the TPM treatment for 1 month in developing brains reduced the SE- induced hippocampal damage. CONCLUSION:TPM has a neuroprotective action, which might be mediated by the modulation of GluR1 and GABAA receptors.
