Neuronal oxidative stress in acute ischemic stroke: Sources and contribution to cell injury

Abstract

Oxidative stress has emerged as a key deleterious factor in brain ischemia and reperfusion. Malfunction of the oxidative respiratory chain in mitochondria combines with the activation of cytoplasmic oxidases to generate a burst of reactive oxygen species that cannot be neutralised by the cell’s antioxidant mechanisms. As a result, oxidative stress contributes directly to necrosis and apoptosis through a number of pathways in ischemic tissue. Pharmacological intervention with antioxidants or enhancers of endogenous antioxidant molecules is proving to be difficult due to the speed and scope of the oxidative impact. Additionally, the knowledge that neuronal fate in ischemic stroke is tightly linked to other brain cells like endothelial cells and astrocytes has shifted the focus of study from isolated neurons to the neurovascular unit. For this reason, recent efforts have been directed towards understanding the sources of oxidative stress in ischemic stroke and attempting to block the generation of oxygen radicals.