Tristan Baumann, Nicole de Buhr, Nicole Blume, Maria M Gabriel, Johanna Ernst, Leonie Fingerhut, Rabea Imker, Omar Abu-Fares, Mark Kühnel, Danny D Jonigk, Friedrich Götz, Christine Falk, Karin Weissenborn, Gerrit M Grosse, Ramona Schuppner
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引用次数: 0
Abstract
Inflammation including immunothrombosis by neutrophil extracellular traps (NETs) has important implications in acute ischemic stroke and can affect reperfusion status, susceptibility to stroke associated infections (SAI) as well as functional clinical outcome. NETs were shown to be prevalent in stroke thrombi and NET associated markers were found in stroke patients' blood. However, little is known whether blood derived NET markers reflect the amount of NETs in thrombi. Conclusions from blood derived markers to thrombus composition might open avenues for novel strategies in diagnostic and therapeutic approaches. We prospectively recruited 166 patients with acute ischemic stroke undergoing mechanical thrombectomy between March 2018 and May 2021. Available thrombi (n = 106) were stained for NET markers DNA-histone-1 complexes and myeloperoxidase (MPO). Cell free DNA (cfDNA), deoxyribonuclease (DNase) activity, MPO-histone complexes and a cytokine-panel were measured before thrombectomy and after seven days. Clinical data, including stroke etiology, reperfusion status, SAI and functional outcome after rehabilitation, were collected of all patients. NET markers were present in all thrombi. At onset the median concentration of cfDNA in blood was 0.19 µg/ml increasing to 0.30 µg/ml at 7 days. Median DNase activity at onset was 4.33 pmol/min/ml increasing to 4.96 pmol/min/ml at 7 days. Within thrombi DNA-histone-1 complexes and MPO correlated with each other (ρ = 0.792; p < 0.001). Moreover, our study provides evidence for an association between the amount of NETs and endogenous DNase activity in blood with amounts of NETs in cerebral thrombi. However, these associations need to be confirmed in larger cohorts, to investigate the potential clinical implications for individualized therapeutic and diagnostic approaches in acute ischemic stroke.
期刊介绍:
The Journal of Thrombosis and Thrombolysis is a long-awaited resource for contemporary cardiologists, hematologists, vascular medicine specialists and clinician-scientists actively involved in treatment decisions and clinical investigation of thrombotic disorders involving the cardiovascular and cerebrovascular systems. The principal focus of the Journal centers on the pathobiology of thrombosis and vascular disorders and the use of anticoagulants, platelet antagonists, cell-based therapies and interventions in scientific investigation, clinical-translational research and patient care.
The Journal will publish original work which emphasizes the interface between fundamental scientific principles and clinical investigation, stimulating an interdisciplinary and scholarly dialogue in thrombosis and vascular science. Published works will also define platforms for translational research, drug development, clinical trials and patient-directed applications. The Journal of Thrombosis and Thrombolysis'' integrated format will expand the reader''s knowledge base and provide important insights for both the investigation and direct clinical application of the most rapidly growing fields in medicine-thrombosis and vascular science.