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.
Keywords: annexin A1; neutrophils; platelets; resolution; stroke; thromboinflammation.