Cellular mechanism of seizure discharge and its normalization by a herbal mixture prescription "Saikokeishito-ka-Shakuyaku" (SK)

Abstract

Epilepsy is one of the most frequently occurring nervous diseases. However, the fundamental cause of epilepsy is still unclear. We tried to elucidate the cellular mechanism of seizure discharge. During this research we unexpectedly found that a herbal mixture prescription shows very good effects on epileptics. Therefore, we also performed experiments on the anticonvulsant mechanism of this herbal mixture prescription, "Saikokeishito-ka-Shakuyaku" (SK). SK showed normalizing effects on intracellular calcium-related and protein-related pathological changes induced by pentylenetetrazol (PTZ) application in snail neurons and cultured neurons from the cerebral cortex of mice. In addition, SK showed marked protective effects against neuron damage induced by the cobalt focus epilepsy model, cytochalasin B and severe stress. SK also showed normalizing effects on developmental defects of cultured neurons from the cerebral cortex of an epilepsy animal model, EL mice. Moreover, SK showed complete preventive effects on the abnormal expression of one of the seizure-related (SEZ) genes, PTZ-17, induced by PTZ in Xenopus oocytes injected with PTZ-17 RNA. We also determined mouse chromosomal loci of the SEZ gene group and PTZ sensitive trait loci by linkage analysis for comparison with human synteny of epileptic families. The above-mentioned findings suggest that some herbal prescriptions will become promising drugs for the therapy against intractable nervous diseases which can not be ameliorated by pure chemical drugs in the future.