Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

INTRODUCTION: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins-pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. AIM: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. MATERIAL AND METHODS: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: 'stroke and lipoxin' and 'stroke and atherosclerosis', resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. RESULTS: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood-brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1ß, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog-BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood-brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. CONCLUSIONS: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

The Role of Resolvins: EPA and DHA Derivatives Can Be Useful in the Prevention and Treatment of Ischemic Stroke.

INTRODUCTION: Most ischemic strokes develop as a result of atherosclerosis, in which inflammation plays a key role. The synthesis cascade of proinflammatory mediators participates in the process induced in the vascular endothelium and platelets. Resolvins are anti-inflammatory mediators originating from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may improve the prognosis related to atherosclerosis by inhibiting the production of proinflammatory cytokines, limiting neutrophil migration, or positively influencing phagocytosis. Although clinical trials with resolvin in humans after stroke have not been realized, they may soon find application. AIM: The aim of the study was to review the available literature on the scope of the possibilities of the prevention and treatment of stroke with the use of resolvins, EPA and DHA derivatives. MATERIALS AND METHODS: The review features articles published until 31 January 2020. The search for adequate literature was conducted using the keywords: stroke and resolvins. Over 150 articles were found. Studies not written in English, letters to the editor, conference abstracts, and duplicate information were excluded. RESULTS: In several studies using the animal model, the supplementation of resolvin D2 decreased brain damage caused by myocardial infarction, and it reversed the neurological dysfunction of the brain. A decrease in the concentration of proinflammatory cytokines, such as TNF-α, Il-6, and Il-1ß, was also observed, as well as a decrease in the scope of brain damage. In the context of stroke in animals, the treatment with resolvin D2 (RvD2) (injection) has a better effect than supplementation with DHA. CONCLUSIONS: Resolvins are characterised by strong anti-inflammatory properties. Resolvins improve prognosis and decrease the risk of developing cardiovascular disease, consequently lowering the risk of stroke, and may find application in the treatment of stroke.