Oxidative Stress and Its Role in the Pathogenesis of Ischaemic Stroke

Abstract

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.

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

“…Reduced cystathionine‐transsulfuration may impair glutathione production and thereby lead to oxidative stress 7. Oxidative stress can, in turn, further impair endothelial morphology by inactivating nitric oxide,9 in addition to mediating several other biological processes such as lipid peroxidation and induction of vascular lesions 1. Notably, a previous study from a subsample of the current cohort showed that higher plasma cystathionine concentration are related to low levels of reduced glutathione,33 indicating impaired antioxidant defence 7…”

“…Stroke is a leading cause of mortality and long‐term disability in the world and remains a massive public health burden 1. This highlights a pressing need to identify novel risk associations for stroke and improve our current understanding of its underlying pathophysiology.…”

“…Notably, elevated circulating cystathionine concentrations were observed in patients with cardiovascular disease (CVD),6 and increased levels were associated with oxidative damage7 and endothelial dysfunction 4, 8. Both these processes play a critical role in the pathogenesis of atherosclerotic disease9 and hence to clinical manifestations such as ischemic stroke 1, 10. Moreover, increased expression of cystathionine metabolizing enzymes have recently been found in human atherosclerotic lesions and are shown to exacerbate angiogenesis, thereby increasing the risk of plaque instability,11 often associated with atherothrombotic events 12.…”

Short‐Term Exposure to Air Pollution and Biomarkers of Oxidative Stress: The Framingham Heart Study

“…Oxidative stress, an imbalance between the production of the reactive oxygen species and the human body's antioxidant defense mechanism,4 has been proposed as an important underlying biological mechanism mediating this association 3, 5, 6, 7. Increased oxidative stress may induce endothelial dysfunction, which is characterized by increased endothelial permeability, altered vascular tone, platelet adhesion and aggregation, and enhanced thrombogenicity 8, 9…”

Left atrial size and risk of recurrent ischemic stroke in a Chinese population

“…It is characterized by high morbidity, high mortality, and a high recurrence rate therefore posing a significant burden on health resources. Ischemic stroke is the most common type of stroke that accounts for almost 80–85% of all stroke cases and is brought about by cutting off cerebral blood flow and thereby oxygen to the brain (Allen & Bayraktutan, 2009). Although a variety of risk factors have been established for ischemic stroke, about 25% of stroke cases are considered cryptogenic (Fonseca & Ferro, 2015).…”