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Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke

Authors
  • Essig, Fabian1
  • Kollikowski, Alexander M.2
  • Pham, Mirko2
  • Solymosi, László2
  • Stoll, Guido1
  • Haeusler, Karl Georg1
  • Kraft, Peter1, 3
  • Schuhmann, Michael K.1
  • 1 (P.K.)
  • 2 (L.S.)
  • 3 Department of Neurology, Klinikum Main-Spessart, 97816 Lohr, Germany
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Oct 07, 2020
Volume
21
Issue
19
Identifiers
DOI: 10.3390/ijms21197387
PMID: 33036337
PMCID: PMC7582743
Source
PubMed Central
Keywords
License
Green

Abstract

Ischemic stroke caused by thromboembolic occlusion of large cerebral arteries, such as the internal carotid (ICA) and/or the middle cerebral artery (MCA), is treated by mechanical thrombectomy (MT). MT allows salvage of the vessel-occluding thrombemboli, which most frequently originate from the left atrium or the left ventricle of the heart or from sites of plaque rupture within large arteries above the heart. Clot composition may influence the efficacy of (intravenous) thrombolysis and MT, respectively. We analyzed 37 human thrombemboli obtained from acute ischemic stroke patients during MT with special emphasis on histological staining of neutrophils and neutrophil extracellular traps (NETs). We found neutrophils as the main cellular component of cerebral thrombemboli but encountered considerable morphological heterogeneity. Neutrophils accumulated in the border region of fibrin-rich structures indicating possible interaction of neutrophils with distinct structural thrombembolus components. Web-like NETs were found in 35 of 37 thrombemboli in varying amounts. NETs were almost exclusively found within fibrin-rich areas. Importantly, stroke etiology, age and present oral anticoagulation was associated with morphological patterns and the amount of neutrophils. Correlation of histological data and imaging data revealed that relative Hounsfield units of cerebral thrombemboli positively correlated with the amount of red blood cells. In summary, our results demonstrate that neutrophils and NETs are substantial constituents of cerebral thrombemboli and contribute to their structural complexity.

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