Some aspects of the mechanisms of epilepsy

Another important milestone was marked by the characterization of the molecular structure of ionic channels that made it clear the tremendous potential of a strategy based on combined neurophysiological and biomolecular techniques for investigating the pathogenesis of human epilepsies. For many years, the ionic currents responsible for membrane excitability have been systematically characterized in intact animals and different animal models of epilepsy, as well as in tissue slices and isolated cell preparations. Neurons and neural circuits undergo extensive structural and functional remodeling in response to seizures. Sprouting of axons in the mossy fiber pathway of the hippocampus is a prominent example of a seizure-induced structural alteration. Several key steps have been identified in the cascade leading from transient hyperactivity episodes to long-lasting, quasi-permanent modification of the neuronal circuit organization (activation of immediate-early genes, activation of growth factor genes within hours, alterations in glutamate receptors, glial hypertrophy, cytoskeletal protein changes, etc). The cascade is activated by the increase in intracellular calcium and leads to axonal growth and neosynapse formation, which in turn participates in the etiology of the syndrome by reducing the threshold for further seizures. Aberrant neuron plasticity is a contributing factor to neurological and developmental disorders. Indeed, aberrant sprouting following neuronal injury may be the cause of epilepsy and may underlie the neuronal changes in other neurological diseases, thus forming a common ground for different pathologies in neurology. Investigation of mechanisms of epilepsy progression, with current theories and perspectives from neuroplasticity in adulthood and development are providing new insights into systematic neurobiological processes that are likely to influence the progressive features of epileptic syndromes and patterns of progression in individual patients