title: Oxidative Stress and the Use of Antioxidants in Stroke.
abstract: Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA). The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS) over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease.
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. Rachel.Shirley@glasgow.ac.uk.
authors.forename: Rachel
authors.initials: R
authors.lastname: Shirley
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. Emily.Ord@glasgow.ac.uk.
authors.forename: Emily N J
authors.initials: EN
authors.lastname: Ord
authors.affiliation: Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. Lorraine.Work@glasgow.ac.uk.
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Work
keywords: anti-oxidant; oxidative stress; stroke