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Trends in Developmental Biology   Volumes    Volume 1 
Intracellular mechanism of seizure discharge –Tentative proposal for a new paradigm of preventive therapy against epilepsy
Eiichi Sugaya, Aiko Sugaya
Pages: 1 - 25
Number of pages: 25
Trends in Developmental Biology
Volume 1 

Copyright © 2005 Research Trends. All rights reserved


To elucidate the fundamental mechanism of seizure discharge, intracellular events including gene expression changes during PTZ-induced seizure discharge were investigated. Finally, based on these experimental findings, we prepared a proposal for tentative preventive therapy against epilepsy.

During bursting activity, intracellular calcium is released and move towards the inner surface of cell membrane, and binds to a substance that does not exist in the normal state. Consequently, the ion channel state is changed and evokes bursting activity. 

Using a differential hybridization method between pentylentetrazol-treated and normal neurons, we found seizure-related genes, the SEZ gene group, which probably play roles in evoking seizure discharge.  Among them, the SEZ-17 (PTZ-17) gene plays the role of regulating intracellular calcium and calcium current.  The grade of calcium entry is regulated by 3’-UTR of SEZ-17. 

Herbal mixture prescription, SK (mixture prescription of Bupleuri Radix, Cinamomi Cortex, Paeoniae Radix, Zingiberis Rhizoma, Glycyrrhzae Radix, Ginseng Radix, Scutellariae Radix, Pinelliae Tuber and Zizyphi Fructus) showed a complete protective effect against severe neuron damage due to the cobalt focus epilepsy model. Developmental defects of the EL mouse cultured neuron were markedly improved by SK application. SK and its component, peony root extract, showed clear normalization of adverse expression of the SEZ-17 gene. 

In  the  future,   considering  these  results,  it  is necessary to create the “third medicine” based on actual western medicine and oriental medicine but is a completely different paradigm than these two medicines, since only with western medicine, we cannot realize adequate neuron protection, improvement of developmental defect and regulation of adverse expression of genes without any side effects.

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