Oxidative stress and its role in the pathogenesis of ischaemic stroke.
Stroke is one of the leading causes of mortality and morbidity, with astronomical financial repercussions on health systems worldwide. Ischaemic stroke accounts for approximately 80-85% of all cases and is characterised by the disruption of cerebral blood flow and lack of oxygen to the affected area. Oxidative stress culminates due to an imbalance between pro-oxidants and antioxidants and consequent excessive production of reactive oxygen species. Reactive oxygen species are biphasic, playing a role in normal physiological processes and are also implicated in a number of disease processes, whereby they mediate damage to cell structures, including lipids, membranes, proteins, and DNA. The cerebral vasculature is a major target of oxidative stress playing a critical role in the pathogenesis of ischaemic brain injury following a cerebrovascular attack. Superoxide, the primary reactive oxygen species, and its derivatives have been shown to cause vasodilatation via the opening of potassium channels and altered vascular reactivity, breakdown of the blood-brain barrier and focal destructive lesions in animal models of ischaemic stroke. However, reactive oxygen species are involved in normal physiological processes including cell signalling, induction of mitogenesis, and immune defence. Primarily, this review will focus on the cellular and vascular aspects of reactive oxygen and nitrogen species generation and their role in the pathogenesis of ischaemia-reperfusion phenomena. Secondly, the proposed mechanisms of oxidative stress-related neuronal death will be reflected upon and in summation specific targeted neuroprotective therapies targetting oxidative stress and their role in the pathogenesis of stroke will be discussed.
Allen
C L
CL
Division of Stroke Medicine, University of Nottingham, Nottingham, UK. claire.allen@nottingham.ac.uk
Bayraktutan
U
U
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers; D001921:Brain / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D002986:Clinical Trials as Topic; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020521:Stroke / Q000209:etiology* / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control
D000975:Antioxidants; D015415:Biomarkers; D017382:Reactive Oxygen Species