Implication of oxidative stress and "labile iron" in the molecular mechanisms of ischemic stroke

Abstract

Strong experimental data support the notion that excessive generation of reactive free radicals takes place in the ischemic area following a stroke episode and that these radicals are responsible for a substantial part of brain injury. However, the exact biochemical mechanisms underlying brain cell damage remain elusive, thus hindering the attempts for development of effective therapeutic strategies. In this presentation, the molecular mechanisms of tissue damage in relation to temporal and spatial generation of "reactive oxygen species" are considered. The mechanisms of oxidant-mediated brain damage are discussed and the role of "labile iron" in this process is evaluated. Although oxygen based oxidants are generated during all phases, their sources and intensities as well as their temporal and spatial generation differ considerably among different phases in stroke. Based on the above considerations, it is proposed that administration of appropriate "labile iron" chelating agents, preferentially prior to reperfusion, might improve the efficacy of any therapeutic strategy.