J Korean Child Neurol Soc.  2006 Nov;14(2):193-206.

The Effect of Topiramate on Status Epilepticus-Induced Neurotoxicity in Immature Mouse Brain

• Park SS
• Bae HR
• Hwang KG

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.

Keyword

Topiramate; Status epilepticus; Neurotoxicity; AMPA glutamate receptor; GABA receptor

MeSH Terms

Animals
Brain*
Butyric Acid
Glutamic Acid
Hippocampus
Mice*
Microscopy, Confocal
Neurons
Receptors, GABA
Status Epilepticus
Up-Regulation
Butyric Acid
Glutamic Acid
Receptors, GABA