Free radicals as triggers of brain edema formation after stroke

Brain edema is a leading cause of death after stroke. Cytotoxic edema, which is most severe in astrocytes, begins within a few minutes of adenosine triphosphate depletion and reflects the ultimate infarct size. Vasogenic edema is caused by uncontrolled fluid leakage from the blood to the brain parenchyma through a weakened blood-brain barrier (BBB) and contributes to an actual net volume increase of the brain, which often leads to death. Recent research on ischemia-induced injury mechanisms of the microvasculature has led to the disclosure of the mechanisms and cellular pathways leading to BBB breakdown. In addition, the introduction of magnetic resonance imaging to clinical practice has enabled the evaluation of edema severity in stroke patients and differentiation between cytotoxic and vasogenic edema. Free radicals exert their deleterious actions during both cytotoxic and vasogenic edema. They can contribute to BBB disruption directly and can also trigger molecular pathways related to the dysfunction of ion transporters in the cell membrane and those related to increased vascular permeability. The development of effective therapeutic strategies aimed at reducing brain edema based on targeting specific molecular pathways involved may reduce death and disability from stroke. (c) 2005 Elsevier Inc. All rights reserved.