Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke
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...
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| Veröffentlicht in: | International journal of molecular sciences 2020-10, Vol.21 (19), p.7387 |
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| description | 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. |
| doi_str_mv | 10.3390/ijms21197387 |
| format | Article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21197387</identifier><identifier>PMID: 33036337</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aged ; Anticoagulants ; Atria ; Blood clots ; Cerebral blood flow ; Collagen ; Deoxyribonucleic acid ; Diagnostic Imaging ; DNA ; Erythrocytes ; Etiology ; Extracellular Traps - immunology ; Extracellular Traps - metabolism ; Female ; Fibrin ; Fluorescent Antibody Technique ; Health aspects ; Heterogeneity ; Histopathology ; Humans ; Immunohistochemistry ; Intravenous administration ; Ischemia ; Leukocytes (neutrophilic) ; Male ; Middle Aged ; Morphology ; Neutrophils ; Neutrophils - pathology ; Occlusion ; Physiological aspects ; Quantitative analysis ; Stroke ; Stroke (Disease) ; Stroke - etiology ; Stroke - pathology ; Stroke - therapy ; Thrombectomy ; Thromboembolism ; Thromboembolism - complications ; Thromboembolism - diagnosis ; Thromboembolism - etiology ; Thromboembolism - therapy ; Thrombolysis ; Treatment Outcome ; Ventricle</subject><ispartof>International journal of molecular sciences, 2020-10, Vol.21 (19), p.7387</ispartof><rights>COPYRIGHT 2020 MDPI AG</rights><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-624680dc2a307c23b7de2e23861d2c473dd093a8a57b4a5648bdd0574e366f243</citedby><cites>FETCH-LOGICAL-c479t-624680dc2a307c23b7de2e23861d2c473dd093a8a57b4a5648bdd0574e366f243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582743/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582743/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33036337$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Essig, Fabian</creatorcontrib><creatorcontrib>Kollikowski, Alexander M</creatorcontrib><creatorcontrib>Pham, Mirko</creatorcontrib><creatorcontrib>Solymosi, László</creatorcontrib><creatorcontrib>Stoll, Guido</creatorcontrib><creatorcontrib>Haeusler, Karl Georg</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Schuhmann, Michael K</creatorcontrib><title>Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>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.</description><subject>Aged</subject><subject>Anticoagulants</subject><subject>Atria</subject><subject>Blood clots</subject><subject>Cerebral blood flow</subject><subject>Collagen</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnostic Imaging</subject><subject>DNA</subject><subject>Erythrocytes</subject><subject>Etiology</subject><subject>Extracellular Traps - immunology</subject><subject>Extracellular Traps - metabolism</subject><subject>Female</subject><subject>Fibrin</subject><subject>Fluorescent Antibody Technique</subject><subject>Health aspects</subject><subject>Heterogeneity</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intravenous administration</subject><subject>Ischemia</subject><subject>Leukocytes (neutrophilic)</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morphology</subject><subject>Neutrophils</subject><subject>Neutrophils - pathology</subject><subject>Occlusion</subject><subject>Physiological aspects</subject><subject>Quantitative analysis</subject><subject>Stroke</subject><subject>Stroke (Disease)</subject><subject>Stroke - etiology</subject><subject>Stroke - pathology</subject><subject>Stroke - therapy</subject><subject>Thrombectomy</subject><subject>Thromboembolism</subject><subject>Thromboembolism - complications</subject><subject>Thromboembolism - diagnosis</subject><subject>Thromboembolism - etiology</subject><subject>Thromboembolism - therapy</subject><subject>Thrombolysis</subject><subject>Treatment Outcome</subject><subject>Ventricle</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptks9vFCEUxydGY2v15tmQePHgVobHwMzFZLNp7SaNHlzPhGGYXVZ-rDAYe_Q_L5PWujWGA_D4vG9433yr6nWNzwE6_MHsXSJ13XFo-ZPqtKaELDBm_OnR-aR6kdIeYwKk6Z5XJwAYGAA_rX6vncs-7Eyagg1bo6RFSy_tTTIJhRF91nmK4bAzNiHph6M7uvg1Ram0tdnKiDZRHhIyHl1lJz3a7GJwvXZ9sAatZE7Gb9FS5UmjdVI77YxCX4vSd_2yejZKm_Sr-_2s-nZ5sVldLa6_fFqvltcLRXk3LRihrMWDIhIwVwR6PmiiCbSsHkhBYBhwB7KVDe-pbBht-1JpONXA2EgonFUf73QPuXd6UNqX71txiMbJeCOCNOLxizc7sQ0_BW9awikUgXf3AjH8yDpNwpk0zy-9DjkJQmnXNUBoV9C3_6D7kGOxtVANbVlLOaZ_qa20Whg_htnQWVQsGSUd1B2Ztc7_Q5U1zCYGr0dT6o8a3t81qBhSinp8mLHGYo6MOI5Mwd8c-_IA_8kI3AL3Kb3D</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Essig, Fabian</creator><creator>Kollikowski, Alexander M</creator><creator>Pham, Mirko</creator><creator>Solymosi, László</creator><creator>Stoll, Guido</creator><creator>Haeusler, Karl Georg</creator><creator>Kraft, Peter</creator><creator>Schuhmann, Michael K</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201001</creationdate><title>Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke</title><author>Essig, Fabian ; Kollikowski, Alexander M ; Pham, Mirko ; Solymosi, László ; Stoll, Guido ; Haeusler, Karl Georg ; Kraft, Peter ; Schuhmann, Michael K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-624680dc2a307c23b7de2e23861d2c473dd093a8a57b4a5648bdd0574e366f243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Anticoagulants</topic><topic>Atria</topic><topic>Blood clots</topic><topic>Cerebral blood flow</topic><topic>Collagen</topic><topic>Deoxyribonucleic acid</topic><topic>Diagnostic Imaging</topic><topic>DNA</topic><topic>Erythrocytes</topic><topic>Etiology</topic><topic>Extracellular Traps - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Essig, Fabian</au><au>Kollikowski, Alexander M</au><au>Pham, Mirko</au><au>Solymosi, László</au><au>Stoll, Guido</au><au>Haeusler, Karl Georg</au><au>Kraft, Peter</au><au>Schuhmann, Michael K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>21</volume><issue>19</issue><spage>7387</spage><pages>7387-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33036337</pmid><doi>10.3390/ijms21197387</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Anticoagulants Atria Blood clots Cerebral blood flow Collagen Deoxyribonucleic acid Diagnostic Imaging DNA Erythrocytes Etiology Extracellular Traps - immunology Extracellular Traps - metabolism Female Fibrin Fluorescent Antibody Technique Health aspects Heterogeneity Histopathology Humans Immunohistochemistry Intravenous administration Ischemia Leukocytes (neutrophilic) Male Middle Aged Morphology Neutrophils Neutrophils - pathology Occlusion Physiological aspects Quantitative analysis Stroke Stroke (Disease) Stroke - etiology Stroke - pathology Stroke - therapy Thrombectomy Thromboembolism Thromboembolism - complications Thromboembolism - diagnosis Thromboembolism - etiology Thromboembolism - therapy Thrombolysis Treatment Outcome Ventricle |
| title | Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke |
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