Angela Genchi1, Aurora Semerano1, Giorgia Serena Gullotta2, Davide Strambo3, Ghil Schwarz4, Andrea Bergamaschi2, Pietro Panni5, Franco Simionato5, Francesco Scomazzoni5, Caterina Michelozzi5, Mattia Pozzato1, Norma Maugeri6, Giancarlo Comi4, Andrea Falini5, Luisa Roveri4, Massimo Filippi4, Gianvito Martino1, Marco Bacigaluppi7. 1. Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. 2. Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. 3. Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 4. Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. 5. Neuroradiology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. 6. Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. 7. Neuroimmunology Unit, Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy; Neurology Department, IRCCS San Raffaele Institute and University Vita- Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Electronic address: bacigaluppi.marco@hsr.it.
Abstract
BACKGROUND: Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT). METHODS: We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus. RESULTS: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62). CONCLUSION: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
BACKGROUND:Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT). METHODS: We performed a systematic histological analysis on 80 humancerebral thrombi retrieved through EVT in acute ischemic strokepatients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus. RESULTS: Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62). CONCLUSION: Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.
Authors: Tetsuya Hashimoto; Takenobu Kunieda; Tristan Honda; Fabien Scalzo; Latisha K Sharma; Jason D Hinman; Neal M Rao; May Nour; Mersedeh Bahr-Hosseini; Jeffrey L Saver; Radoslav Raychev; David S Liebeskind Journal: Neuroradiol J Date: 2021-10-05