The role of mitochondria and oxidative stress in neuronal damage after brief and prolonged seizures

Abstract

Studies in vitro and in other disease states where excitotoxicity is believed to be important have demonstrated that mitochondrial function is a critical determinant of cell death, reflecting key roles in intracellular calcium homeostasis, energy production and oxidative stress. Central to this is the process of mitochondrial permeability transition, for which there are numerous influencing factors, although many, if not all, may specifically act though effects on the redox state of the cell and oxidative stress. Mitochondrial function in relation to seizure-induced cell death has been little studied until recently, but there is now accumulating evidence that similar mechanisms operate, certainly in cell death, following prolonged seizures. To what extent these same mechanisms might contribute to non-fatal but pathologically significant functional cellular changes in epilepsy, and the significance of reported free radical production after brief seizures is as yet uncertain. However, with the wide range of established techniques available to study mitochondrial function and oxidative stress, and those currently under development, these questions are undoubtedly answerable in the near future. Increased understanding of the mechanisms involved in seizure-induced cellular damage is an essential basis for the development of rational neuroprotective strategies.