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Open Access 09-06-2024 | Stroke

Assessment of associations between neutrophil extracellular trap biomarkers in blood and thrombi in acute ischemic stroke patients

Authors: 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

Published in: Journal of Thrombosis and Thrombolysis

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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.

Graphical Abstract

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Literature
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go back to reference Dargazanli C, Fahed R, Blanc R et al (2018) Modified thrombolysis in cerebral infarction 2C/thrombolysis in cerebral infarction 3 reperfusion should be the aim of mechanical thrombectomy: insights from the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Stroke 49(5):1189–1196. https://doi.org/10.1161/STROKEAHA.118.020700CrossRefPubMed Dargazanli C, Fahed R, Blanc R et al (2018) Modified thrombolysis in cerebral infarction 2C/thrombolysis in cerebral infarction 3 reperfusion should be the aim of mechanical thrombectomy: insights from the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Stroke 49(5):1189–1196. https://​doi.​org/​10.​1161/​STROKEAHA.​118.​020700CrossRefPubMed
23.
Metadata
Title
Assessment of associations between neutrophil extracellular trap biomarkers in blood and thrombi in acute ischemic stroke patients
Authors
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
Publication date
09-06-2024
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-024-03004-y
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