Neutrophil extracellular traps: A novel target for the treatment of stroke

Stroke is a threatening cerebrovascular disease caused by thrombus with high morbidity and mortality rates. Neutrophils are the first to be recruited in the brain after stroke, which aggravate brain injury through multiple mechanisms. Neutrophil extracellular traps (NETs), as a novel regulatory mechanism of neutrophils, can trap bac-teria and secret antimicrobial molecules, thereby degrading pathogenic factors and killing bacteria. However, NETs also exacerbate certain non-infectious diseases by activating autoimmune or inflammatory responses. NETs have been found to play important roles in the pathological process of stroke in recent years. In this review, the mechanisms of NETs formation, the physiological roles of NETs, and the dynamic changes of NETs after stroke are summarized. NETs participate in stroke through various mechanisms. NETs promote the coagulation cascade and interact with platelets to induce thrombosis. tPA induces the degranulation of neutrophils to form NETs, lead-ing to hemorrhagic transformation and thrombolytic resistance. NETs aggravate stroke by mediating inflamma-tion, atherosclerosis and vascular injury. In addition, the regulation of NETs in stroke, the potential of NETs as biomarker and the treatment of stroke targeting NETs are discussed. The increasing evidences suggest that NETs may be a potential target for stroke treatment. Inhibition of NETs formation or promotion of NETs degrada-tion plays protective effects in stroke. However, how to avoid the adverse effects of NETs-targeted therapy de-serves further study. In summary, this review provides a reference for the pathogenesis, drug targets, biomarkers and drug development of NETs in stroke.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Stroke is a cerebrovascular disease caused by thrombus, with high morbidity and mortality rates. Neutrophils are the first cells to be recruited in the brain after stroke, and they aggravate brain injury through multiple mechanisms. Neutrophil extracellular traps (NETs) have been found to play important roles in the pathological process of stroke in recent years.