The epsilon theory: A novel synthesis of the underlying molecular and electrophysiological mechanisms of primary generalized epilepsy and the possible mechanism of action of valproate

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Abstract

Primary generalized epilepsy may be the result of maldevelopment of central nervous system and each seizure may be the consequence of a neuronal maladaptation to an unknown stimulus using the paleospinothalamical tract due to an overexpression of brain-derived neurotrophic factor and neurotrophin-3. The subsequent protein kinase C ε (PKC-ε) activation and intracellular Ca 2+ release causes a nociceptive hypersensitization and an increased cortical hyperexcitability because of increased frequency of synchronous Ca 2+ oscillations, cortical maldevelopment at the level of synapses and an attenuation of GABA A receptor mediated responses in reticular thalamic nucleus. Valproate may exert its antiepileptic effect as a PKC-ε inhibitor, and using with a PKC-ε activator that cannot pass blood brain barrier, its side effects may become avoidable.

Original languageEnglish
Pages (from-to)267-272
Number of pages6
JournalMedical hypotheses
Volume64
Issue number2
DOIs
Publication statusPublished - Jan 7 2005

ASJC Scopus subject areas

  • Medicine(all)

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