Abstract
Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke.
Highlights
The understanding and the therapeutic approach to stroke has remarkably transformed in the past few decades [1]
Neutrophilderived P-selectin glycoprotein ligand-1 (PSGL-1) and platelet P-selectin drive Neutrophil–platelet aggregate (NPA) development resulting in the activation Mac-1and LFA-1 (Mac-1 and LFA-1 are two β2 integrins expressed on neutrophils and mediate the recruitment cascade by binding to intercellular adhesive molecule 1 (ICAM-1)) [15,16]
Neutrophils and platelets are seen as key players in thromboinflammation and the pathogenesis of stroke
Summary
The understanding and the therapeutic approach to stroke has remarkably transformed in the past few decades [1]. Acute cerebral ischemia induces a strong immune response resulting in recruitment of several subsets of leukocytes (mainly neutrophils), activation of platelets, and coagulation cascade and upregulation of cell adhesion molecules and cytokines [10]. Neutrophilderived P-selectin glycoprotein ligand-1 (PSGL-1) and platelet P-selectin drive NPA development resulting in the activation Mac-1and LFA-1 (Mac-1 and LFA-1 are two β2 integrins expressed on neutrophils and mediate the recruitment cascade by binding to intercellular adhesive molecule 1 (ICAM-1)) [15,16]. We show the major neutrophil–plateGPIbα, and Mac-1-α. Thrombus above activation recruitment in continuous of stimulated of stimulatedplatelets, neutrophils, and red and blood cells, andofactivation of the coagulation cascade.oxygen. Neutrophil elastase enhance coagulation cascade bycascade inhibiting tissue factor pathway inhibitor (TFPI).
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