Role of polyunsaturated fatty acids in ischemic stroke – A perspective of specialized pro-resolving mediators

Abstract

Polyunsaturated fatty acids (PUFAs) have been proposed as beneficial for cardiovascular health. However, results from both epidemiological studies and clinical trials have been inconsistent, whereas most of the animal studies showed promising benefits of PUFAs in the prevention and treatment of ischemic stroke. In recent years, it has become clear that PUFAs are metabolized into various types of bioactive derivatives, including the specialized pro-resolving mediators (SPMs). SPMs exert multiple biofunctions, such as to limit excessive inflammatory responses, regulate lipid metabolism and immune cell functions, decrease production of pro-inflammatory factors, increase anti-inflammatory mediators, as well as to promote tissue repair and homeostasis. Inflammation has been recognised as a key contributor to the pathophysiology of acute ischemic stroke. Owing to their potent pro-resolving actions, SPMs are potential for development of novel anti-stroke therapy. In this review, we will summarize current knowledge of epidemiological studies, basic research and clinical trials concerning PUFAs in stroke prevention and treatment, with special attention to SPMs as the unsung heroes behind PUFAs.

Plasma Lipid Mediators Associate With Clinical Outcome After Successful Endovascular Thrombectomy in Patients With Acute Ischemic Stroke

“…Effective resolution of excessive and uncontrolled inflammation is essential for balancing cerebral I/R-induced neuroinflammation to restore brain homeostasis and to avoid neurological impairments ( 8 – 10 ). For example, cells subjected to brain ischemia accumulate PUFAs and their metabolites lipid mediators, which regulate both the pro-inflammatory and the anti-inflammatory/pro-resolving processes ( 12 ). After the onset of AIS, PUFAs are released from the cellular membrane by the activities of phospholipase enzymes (e.g., phospholipase A2), pro-inflammatory classical eicosanoids, including prostaglandins and leukotrienes, are then produced from AA and promote the resident microglial activation, neutrophil infiltration, and vascular permeability.…”

“…Novel biomarkers in neuroinflammation may therefore be of great value in predicting clinical outcomes in patients with AIS after EVT treatment. Recently, the lipid metabolism of the brain, especially that of polyunsaturated fatty acids (PUFAs) and their bioactive derivatives, has emerged as a key process of the neuroinflammation related to cerebral I/R injury ( 12 ). PUFAs are structural and functional constituents of cellular membranes that are enriched in cells of the central nervous system and that can be further divided into the omega-3 fatty acids such as docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) that are found in fish oil and omega-6 fatty acids [e.g.…”

“…PUFAs are structural and functional constituents of cellular membranes that are enriched in cells of the central nervous system and that can be further divided into the omega-3 fatty acids such as docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) that are found in fish oil and omega-6 fatty acids [e.g. arachidonic acid (AA) and alpha-linoleic acid (ALA)] that are often found in plant oil ( 12 , 13 ). Bioactive lipid mediators are a large family of versatile molecules derived from PUFAs, and are involved in the initiation, progression, and resolution of inflammation.…”

“…These lipid mediators include AA-derived prostaglandins (PGs; e.g., PGE2), leukotrienes (LTs; e.g., LTB4), and thromboxanes (TXs; e.g., TXA2), and an expanding list of newly discovered specialized pro-resolving mediators (SPMs). SPMs are mainly classed as AA-derived lipoxins (LXs; e.g., LXA4), DHA-derived resolvins (RvDs; e.g., RvD1), EPA-derived resolvins (RvEs; e.g., RvE1), neuroprotectins (NPs; e.g., NPD1), and maresins (MaRs; e.g., MaR1) ( 12 , 13 ). These bioactive lipid mediators exert ambivalent role during inflammatory process.…”

Molecular Mechanisms of Neuroimmune Crosstalk in the Pathogenesis of Stroke

“…in the rat MCAO model, leading to a reduction in infarct volume [31,109]. Since resolvins and protectins are generated through omega-3 fatty acid metabolism, dietary fatty-acid supplementation has been investigated for both stroke prevention and intervention but has generated inconsistent results in human clinical trials [110].…”