| The Effect of Topiramate on Status Epilepticus-Induced Neurotoxicity in Immature Mouse Brain. |
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Sang Soo Park, Hae Rahn Bae, Kyu Geun Hwang |
1Department of Pediatrics, Dong-A University Medical School, Busan, Korea. kghyang@dau.ac.kr
2Department of Physiology, Dong-A University Medical School, Busan, Korea. |
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| 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. |
| Key Words:
Topiramate, Status epilepticus, Neurotoxicity, AMPA glutamate receptor, GABA receptor |
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