{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T21:44:08Z","timestamp":1758663848951,"version":"3.44.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Helsinki University Hospital EVO","award":["TYH2021323"],"award-info":[{"award-number":["TYH2021323"]}]},{"name":"Maire Taponen Foundation"},{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010133","name":"Aarne Koskelo Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008320","name":"Finnish Brain Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008320","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007361","name":"Aarne and Aili Turunen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004756","name":"Emil Aaltonen Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004756","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007634","name":"Ida Montin Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007634","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019841","name":"Finnish-Norwegian Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019841","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020364","name":"The Wihuri Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020364","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004022","name":"Jenny and Antti Wihuri Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic inflammation in saccular intracranial aneurysm (sIA) walls is associated with wall rupture. Previous studies have shown an association between macrophages and CD3+ T-lymphocytes with sIA wall degeneration and rupture but the roles of T-lymphocyte subtypes and B-lymphocytes are poorly understood. Here, cyclic multiplexed immunofluorescent staining was used to investigate the presence of T-lymphocytes helper CD4+ and cytotoxic CD8+ T-lymphocytes and CD20+ B-lymphocytes in 16 unruptured and 20 ruptured sIA walls. The sIA walls contained both CD4+ (n\u2009=\u200925\/35) and CD8+ (n\u2009=\u200921\/35) subtypes. There was a greater density of CD4+ T-lymphocytes (median 7, range 0-642 cells\/mm2) vs CD8+ T-lymphocytes (median 1, range 0-30 cells\/mm2). The density of CD4+ T-lymphocytes was associated with wall rupture, the presence of an intraluminal thrombus and numbers of vascular and lymphatic neovessels. Additionally, the densities of CD20+ B- and CD4+ T-lymphocytes were associated with atherosclerosis- and inflammation-related changes, such as the accumulation of apolipoprotein B-100 and serum amyloid A, and densities of CD68+ and CD163+ macrophages. These findings suggest that CD4+ T-lymphocytes play a role in sIA rupture, and that CD4+ T- and CD20+ B-lymphocytes contribute to sIA wall inflammation, particularly in the presence of atherosclerotic changes.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf060","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:16:17Z","timestamp":1749640577000},"page":"870-878","source":"Crossref","is-referenced-by-count":0,"title":["CD4+ T-lymphocytes in human saccular intracranial aneurysm walls are associated with aneurysm rupture"],"prefix":"10.1093","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-757X","authenticated-orcid":false,"given":"Nora","family":"Firtser","sequence":"first","affiliation":[{"name":"Neurosurgery Research Group, Biomedicum 1 , Helsinki,","place":["Finland"]},{"name":"Department of Neurosurgery, Kuopio University Hospital , Kuopio,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliisa","family":"Netti","sequence":"additional","affiliation":[{"name":"Neurosurgery Research Group, Biomedicum 1 , Helsinki,","place":["Finland"]},{"name":"Department of Neurosurgery, Helsinki University Hospital and University of Helsinki , Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-108X","authenticated-orcid":false,"given":"Eliisa","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Translational Immunology Research Program, University of Helsinki, Biomedicum 1 , Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9980-6201","authenticated-orcid":false,"given":"Satu","family":"Lehti","sequence":"additional","affiliation":[{"name":"Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyv\u00e4skyl\u00e4 , Jyv\u00e4skyl\u00e4,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petri T","family":"Kovanen","sequence":"additional","affiliation":[{"name":"Wihuri Research Institute, Atherosclerosis Research Laboratory, Biomedicum 1 , Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-0684","authenticated-orcid":false,"given":"Mika","family":"Niemel\u00e4","sequence":"additional","affiliation":[{"name":"Neurosurgery Research Group, Biomedicum 1 , Helsinki,","place":["Finland"]},{"name":"Department of Neurosurgery, Helsinki University Hospital and University of Helsinki , Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1103-0216","authenticated-orcid":false,"given":"Riikka","family":"Tulamo","sequence":"additional","affiliation":[{"name":"Neurosurgery Research Group, Biomedicum 1 , Helsinki,","place":["Finland"]},{"name":"Department of Vascular Surgery, Helsinki University Hospital and University of Helsinki , Helsinki,","place":["Finland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"2025092317015843700_nlaf060-B1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S1474-4422(09)70126-7","article-title":"Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis","volume":"8","author":"Nieuwkamp","year":"2009","journal-title":"Lancet Neurol"},{"key":"2025092317015843700_nlaf060-B2","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1161\/01.STR.0000140636.30204.da","article-title":"Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured 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