[Neuromechanisms for intractable epilepsy: a review of the studies on the kindling model of epilepsy].

Recent advances in kindling studies were reviewed to search a neurobiological mechanism of the epileptogenesis in intractable epilepsy. Consistent findings that indicate the following three issues were available. First, a long-lasting epileptogenesis can develop acquisitively by the repetition of self-sustained epileptic discharges, which may be produced by recurrent changes in the excitatory amino acid system (EAA) via NMDA receptors. Another brief seizure-induced cascading change that occurs in the third and fourth messenger systems through the metabolic EAA receptor may be critical for the persistence of acquired epileptogenesis. Secondly, an unstable balance between the altered EAAergic facilitatory system and insufficient GABAergic inhibitory system may exist in interictal epileptic disorder. The GABAergic inhibition failure as well as excessive EAA transmission may cause the emergence of epileptic seizures. Thirdly, neuronal sprouting in the mossy fiber of the dentate gyrus and a decrease in the neuronal density in the hilar region seem not to be an essential change for induction of the kindling effect. The clinical validity of these histological changes should be further examined in an over-kindling model sufficient to produce spontaneous seizures.