Neutrophil Extracellular Traps Enhance the Hypercoagulation State in t-PA Thrombolysis in Acute Ischemic Stroke

2021 ◽  
Author(s):  
Jiaqi Jin ◽  
Jie Liu ◽  
Wenqiang Li ◽  
Fang Wang ◽  
Chunxu Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps

Abstract TMP26: Existence of Neutrophil Extracellular Traps in Arterial Thrombi from Patients with Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wei Li ◽  
Huan Wang ◽  
Wuwei Feng ◽  
Meng Zhang
Keyword(s):  
Electron Microscopy ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
White Blood Cells ◽  
Neutrophil Extracellular Traps ◽  
Immunofluorescence Staining ◽  
Large Artery ◽  
Extracellular Traps ◽  
Arterial Thrombus ◽  
Hematoxylin Eosin

Introduction: Neutrophil extracellular traps (NETs) are composed mainly of strands of filamentous DNA and nuclear proteins, such as chromatin or isoforms of histone and secretable neutrophil granular proteins. Recent studies have shown that NETs existed in the venous thrombi and might function as a scaffold and had implication for thrombolytic treatments. Hypothesis: NETs also exists in cerebral arterial thrombus collected from patients with acute ischemic stroke(AIS). Methods: Ten arterial thrombi were collected from 10 AIS patients (33-78 years old, 4 females) who were treated by endovascular therapy (eight of them accepted alteplase thrombolysis firstly)within 8 hours after symptoms onset. Hematoxylin-eosin (HE) staining, immunofluorescence staining (including anti-histone H3 and Hoechst 33342 which label DNA) and electron microscopy were performed to identify the existence of fibrin and/or NETs in thrombus. Results: There were 4 thrombi from middle cerebral artery, 3 from internal carotid artery and 3 from basilar artery. Cardioembolism were considered as etiology for 5 patients and large artery atherosclerosis was the etiology for another 5 patients. HE staining showed that large amounts of fibrin and white blood cells in all ten cerebral arterial thrombi. NETs structures were also identified in 10/10 cerebral arterial thrombi by immunofluorescence staining. Furthermore, the existence of neutrophil-released DNA network together with fibrin was confirmed using electron microscopy in all 10 thrombi. Conclusion: Our results directly demonstrated that NETs do exist in the arterial thrombi from patients with AIS. they may serve as another structural component in addition to fibrin in both cardiogenic and artery atherosclerotic thrombi. NETs can be a new potential target for the recanalization treatment. Keyword: Neutrophil extracellular traps (NETs); arterial thrombus; Acute ischemic stroke

scholarly journals Thrombus Neutrophil Extracellular Traps Content Impair tPA-Induced Thrombolysis in Acute Ischemic Stroke

Stroke ◽  
2018 ◽  
Vol 49 (3) ◽  
pp. 754-757 ◽  
Author(s):  
Celina Ducroux ◽  
Lucas Di Meglio ◽  
Stephane Loyau ◽  
Sandrine Delbosc ◽  
William Boisseau ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps

Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance

2017 ◽  
Vol 117 (10) ◽  
pp. 1919-1929 ◽  
Author(s):  
Juana Vallés ◽  
María Teresa Santos ◽  
Ana María Latorre ◽  
José Tembl ◽  
Juan Salom ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Proteolytic Enzymes ◽  
Demographic Data ◽  
Prognostic Significance ◽  
Neutrophil Extracellular Traps ◽  
Stroke Severity ◽  
Specific Marker ◽  
Glucose Levels ◽  
Extracellular Traps

SummaryNeutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes. The study included 243 patients with acute ischemic stroke. Clinical and demographic data and scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined in plasma. Patients were followed-up for 12 months after the ischemic event. NETs were significantly elevated in the plasma of patients with acute ischemic stroke when compared to healthy subjects. NETs were increased in patients who were over 65 years of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke, high glucose levels, and severe stroke scores at admission and discharge. In multivariate analysis, elevated levels of citH3, the most specific marker of NETs, at onset were independently associated with AF and all-cause mortality at oneyear follow-up. NETs play a role in the pathophysiology of stroke and are associated with severity and mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic target in patients with acute stroke.

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

2020 ◽  
Vol 21 (19) ◽  
pp. 7387
Author(s):  
Fabian Essig ◽  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
László Solymosi ◽  
Guido Stoll ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plaque Rupture ◽  
Cerebral Arteries ◽  
Structural Complexity ◽  
Intravenous Thrombolysis ◽  
Neutrophil Extracellular Traps ◽  
Border Region ◽  
Imaging Data ◽  
Extracellular Traps

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.

Correlation of Neutrophil to Lymphocyte Ratio with Expression of Neutrophil Extracellular Traps Within Stroke Emboli

2021 ◽  
pp. 159101992110655
Author(s):  
Jorge Arturo Larco ◽  
Mehdi Abbasi ◽  
Sarosh Irfan Madhani ◽  
Madalina Oana Mereuta ◽  
Yang Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Cells ◽  
White Blood Cells ◽  
Neutrophil Extracellular Traps ◽  
Vessel Occlusion ◽  
Average Percentage ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Extracellular Traps

Background & Purpose It has been hypothesized that circulating neutrophils have a direct correlation with the composition of emboli in acute ischemic stroke (AIS). The aim of this study is to evaluate the association between neutrophil-lymphocyte ratio (NLR) in peripheral blood and the expression of neutrophil extracellular traps (NETs) within stroke emboli. Methods Consecutive patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) that underwent mechanical thrombectomy (MT) were included. Patients were divided into two groups based on NLR median value. Retrieved thrombi were histologically analyzed using Martius Scarlett Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Immunohistochemistry staining for von Willebrand Factor (vWF) and anti-citrullinated H3 (H3Cit; NETs marker) was also performed. Results Samples from a total of 84 patients were included. The average percentage of RBCs, WBCs, fibrin, platelet, H3Cit, and vWF components in thrombi were 45.1%, 3.5%, 21.8%, 29.6%, 19.7% and 14.8% respectively. When stratifying by NLR group [low (≤3.94) versus high (>3.95)], high NLR group had significantly more WBCs (4.5%), fibrin (24.2%), H3Cit (22.7%) and vWF (17.1%) thrombus fractions compared to low NLR group. Additionally, RBC content (38.8%) was lower in the high NLR group. Conclusions NLR is correlated with the amounts of WBCs, fibrin, NETs and vWF within the thrombi retrieved from AIS patients due to LVO.

scholarly journals Detailed histological analysis of a thrombectomy-resistant ischemic stroke thrombus: a case report

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Senna Staessens ◽  
Olivier François ◽  
Linda Desender ◽  
Peter Vanacker ◽  
Tom Dewaele ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Von Willebrand Factor ◽  
Histological Analysis ◽  
Mechanical Thrombectomy ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Dna ◽  
Extracellular Traps ◽  
First Pass ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background Mechanical removal of a thrombus by thrombectomy can be quite challenging. For reasons that are not fully understood, some thrombi require multiple passes to achieve successful recanalization, whereas other thrombi are efficiently removed in a single pass. Since first pass success is associated with better clinical outcome, it is important to better understand the nature of thrombectomy resistant thrombi. The aim of this study was therefore to characterize the cellular and molecular composition of a thrombus that was very hard to retrieve via mechanical thrombectomy. Case presentation In a patient that was admitted with a right middle cerebral artery M1-occlusion, 11 attempts using various thrombectomy devices and techniques were required for removal of the thrombus. This peculiar case provided a rare opportunity to perform an in-depth histopathological study of a difficult to retrieve thrombus. Thrombus material was histologically analyzed using hematoxylin and eosin, Martius Scarlet Blue stain (red blood cells and fibrin), Feulgen stain (DNA), von Kossa stain (calcifications) and immunohistochemical analysis of von Willebrand factor, platelets, leukocytes and neutrophil extracellular traps. Histological analysis revealed abnormally high amounts of extracellular DNA, leukocytes, von Willebrand factor and calcifications. Extracellular DNA stained positive for markers of leukocytes and NETs, suggesting that a significant portion of DNA is derived from neutrophil extracellular traps. Conclusion In this unique case of a nearly thrombectomy-resistant stroke thrombus, our study showed an atypical composition compared to the common structural features found in ischemic stroke thrombi. The core of the retrieved thrombus consisted of extracellular DNA that colocalized with von Willebrand factor and microcalcifications. These results support the hypothesis that von Willebrand factor, neutrophil extracellular traps and microcalcifications contribute to mechanical thrombectomy resistance. Such information is important to identify novel targets in order to optimize technical treatment protocols and techniques to increase first pass success rates.

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