Targeting Neutrophil Extracellular Traps for Stroke Prognosis: A Promising Path

Author:

Liaptsi Eirini1,Merkouris Ermis1ORCID,Polatidou Efthymia1,Tsiptsios Dimitrios1ORCID,Gkantzios Aimilios1ORCID,Kokkotis Christos2,Petridis Foivos3,Christidi Foteini1,Karatzetzou Stella1,Karaoglanis Christos1,Tsagkalidi Anna-Maria1,Chouliaras Nikolaos1,Tsamakis Konstantinos4ORCID,Protopapa Maria2,Pantazis-Pergaminelis Dimitrios2,Skendros Panagiotis5,Aggelousis Nikolaos2ORCID,Vadikolias Konstantinos1ORCID

Affiliation:

1. Neurology Department, Democritus University of Thrace, 68100 Alexandroupolis, Greece

2. Department of Physical Education and Sport Science, Democritus University of Thrace, 69100 Komotini, Greece

3. Third Department of Neurology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece

4. King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK

5. First Department of Internal Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece

Abstract

Stroke has become the first cause of functional disability and one of the leading causes of mortality worldwide. Therefore, it is of crucial importance to develop accurate biomarkers to assess stroke risk and prognosis. Emerging evidence suggests that neutrophil extracellular trap (NET) levels may serve as a valuable biomarker to predict stroke occurrence and functional outcome. NETs are known to create a procoagulant state by serving as a scaffold for tissue factor (TF) and platelets inducing thrombosis by activating coagulation pathways and endothelium. A literature search was conducted in two databases (MEDLINE and Scopus) to trace all relevant studies published between 1 January 2016 and 31 December 2022, addressing the potential utility of NETs as a stroke biomarker. Only full-text articles in English were included. The current review includes thirty-three papers. Elevated NET levels in plasma and thrombi seem to be associated with increased mortality and worse functional outcomes in stroke, with all acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage included. Additionally, higher NET levels seem to correlate with worse outcomes after recanalization therapies and are more frequently found in strokes of cardioembolic or cryptogenic origin. Additionally, total neutrophil count in plasma seems also to correlate with stroke severity. Overall, NETs may be a promising predictive tool to assess stroke severity, functional outcome, and response to recanalization therapies.

Funder

Study of the interrelationships between neuroimaging, neurophysiological and biomechanical biomarkers in stroke rehabilitation

Support for Regional Excellence

Publisher

MDPI AG

Subject

Neurology (clinical)

Reference53 articles.

1. Thrombosis as an intravascular effector of innate immunity;Engelmann;Nat. Rev. Immunol.,2013

2. GBD 2019 Stroke Collaborators (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol., 20, 795–820.

3. Neutrophil extracellular traps are increased in patients with acute ischemic stroke: Prognostic significance;Santos;Thromb. Haemost.,2017

4. Traps N’ Clots: NET-Mediated Thrombosis and Related Diseases;Stakos;Thromb. Haemost.,2020

5. Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction;Stakos;Eur. Heart J.,2015

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