Neutrophil extracellular traps contribute to tissue plasminogen activator resistance in acute ischemic stroke

Circulating neutrophil extracellular traps (NETs) resistant to t-PA have not been studied completely although NETs in thrombi may contribute tissue plasminogen activator (t-PA) resistance. This research intended elucidate whether circulating are associated with resistance and the underlying mechanism. The levels of were detected neutrophils, ischemic brain acute stroke (AIS) patients, transient middle cerebral artery occlusion (tMCAO) models. NET formation blood, thrombi, mice analyzed by immunofluorescence. Exposed phosphatidylserine (PS) was assessed using flow cytometry confocal microscopy. Procoagulant activity (PCA) evaluated fibrin assays, thrombin, purified coagulation complex. plasma AIS patients significantly higher than those healthy individuals. After thrombolysis, a significant increase noted markers no-improvement while changes improvement significant. Importantly, decorated von Willebrand factor (vWF) inhibitor-1 (PAI-1) blood which could reverse fibrinolytic effects. In addition, activated platelets (PLTs) endothelial cells (ECs), stimulating procoagulant phenotype facilitating vWF PAI-1 release. DNase I, protein C (APC), sivelestat markedly inhibited these Furthermore, targeting protected from tMCAO-induced ischemia, possibly regulating PAI-1. summary, through activation PLTs ECs. Strategies against present promising therapeutic approach improve thrombolysis efficiency patients.