title: The role of free radical generation in increasing cerebrovascular permeability.
abstract: The brain endothelium constitutes a barrier to the passive movement of substances from the blood into the cerebral microenvironment, and disruption of this barrier after a stroke or trauma has potentially fatal consequences. Reactive oxygen species (ROS), which are formed during these cerebrovascular accidents, have a key role in this disruption. ROS are formed constitutively by mitochondria and also by the activation of cell receptors that transduce signals from inflammatory mediators, e.g., activated phospholipase A₂ forms arachidonic acid that interacts with cyclooxygenase and lipoxygenase to generate ROS. Endothelial NADPH oxidase, activated by cytokines, also contributes to ROS. There is a surge in ROS following reperfusion after cerebral ischemia and the interaction of the signaling pathways plays a role in this. This review critically evaluates the literature and concludes that the ischemic penumbra is a consequence of the initial edema resulting from the ROS surge after reperfusion.
authors.affiliation: BHF Centre of Research Excellence, Cardiovascular Division, King's College London, London SE19NH, UK. paul.fraser@kcl.ac.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fraser
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D016207:Cytokines; D005609:Free Radicals; D018836:Inflammation Mediators