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

Biomarkers NETs Neutrophil extracellular traps Stroke Thrombo-inflammation

Journal

Journal of thrombosis and thrombolysis
ISSN: 1573-742X
Titre abrégé: J Thromb Thrombolysis
Pays: Netherlands
ID NLM: 9502018

Informations de publication

Date de publication:
09 Jun 2024
Historique:
accepted: 13 05 2024
medline: 10 6 2024
pubmed: 10 6 2024
entrez: 9 6 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 38853210
doi: 10.1007/s11239-024-03004-y
pii: 10.1007/s11239-024-03004-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s).

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Auteurs

Tristan Baumann (T)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Nicole de Buhr (N)

Institute of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.

Nicole Blume (N)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Maria M Gabriel (MM)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Johanna Ernst (J)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Leonie Fingerhut (L)

Institute of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.

Rabea Imker (R)

Institute of Biochemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.

Omar Abu-Fares (O)

Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.

Mark Kühnel (M)

Institute of Pathology, Hannover Medical School, Hannover, Germany.
Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.

Danny D Jonigk (DD)

Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
Institute of Pathology, RWTH Aachen Medical University, Aachen, Germany.

Friedrich Götz (F)

Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany.

Christine Falk (C)

Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany.

Karin Weissenborn (K)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

Gerrit M Grosse (GM)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland.

Ramona Schuppner (R)

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany. schuppner.ramona@mh-hannover.de.

Classifications MeSH