{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:31:04Z","timestamp":1773721864171,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3 la Marat\u00f3 TV3","award":["248\/C\/2020"],"award-info":[{"award-number":["248\/C\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent studies suggest that blood\u2013brain barrier (BBB) disruption plays a key role in the clinical course and bleeding risk of brain arteriovenous malformations (bAVMs). The tight junctions (TJs) are complex endothelial transmembrane proteins with a significant physical contribution to BBB disruption. In this study, we hypothesized that bAVMs display a different TJ pattern than other vascular malformations and normal brain tissue. We studied the expression of claudin-5 and occludin as essential factors for functional TJs. Human specimens of surgically resected cavernomas (CCMs) (n = 9), bAVMs (n = 17), and perilesional brain parenchyma (6 from CCMs and 16 from bAVM patients) were analyzed via immunofluorescence staining, transmission electron microscopy (TEM), and Western blot tests. Compared to perilesional parenchyma, bAVMs showed a significant decrease in TJ protein expression, and these alterations were more apparent in ruptured bAVMs than in unruptured bAVMs or CCMs. TEM images provided evidence of disrupted connectivity between endothelial cells of bAVMs. This is the first clinical investigation that studies the expression of TJs in human bAVMs and their surrounding parenchyma. Despite the limitations of the sample size, we found significant differences in the expression and composition of TJs in bAVMs when compared to surrounding parenchyma and other vascular lesions such as CCMs. These results add further evidence to the role of BBB disruption in the clinical course of bAVM. A deeper understanding of these mechanisms may lead to the development of new therapeutic targets and management strategies for bAVMs.<\/jats:p>","DOI":"10.3390\/ijms26104558","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T11:25:53Z","timestamp":1746789953000},"page":"4558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Profiling Tight Junction Protein Expression in Brain Vascular Malformations"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1852-4975","authenticated-orcid":false,"given":"Leire","family":"Pedrosa","sequence":"first","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Mosteiro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-7535","authenticated-orcid":false,"given":"Luis","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Amaro","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Comprehensive Stroke Center, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7546-9127","authenticated-orcid":false,"given":"Sebasti\u00e1n","family":"Men\u00e9ndez-Gir\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Germans Trias i Pujol University Hospital, Carretera de Canyet, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mateo Cort\u00e9s","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Germans Trias i Pujol University Hospital, Carretera de Canyet, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5965-8152","authenticated-orcid":false,"given":"Carlos J.","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Germans Trias i Pujol University Hospital, Carretera de Canyet, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-1880","authenticated-orcid":false,"given":"Anna M.","family":"Planas","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Neuroscience and Experimental Therapeutics, Institute for Biomedical Research of Barcelona (IIBB), Spanish Research Council (CSIC), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7932-2528","authenticated-orcid":false,"given":"Ramon","family":"Torn\u00e9","sequence":"additional","affiliation":[{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Department of Neurosurgery, Institute of Neuroscience, Hospital Clinic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2992-2557","authenticated-orcid":false,"given":"Ana","family":"Rodr\u00edguez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Germans Trias i Pujol University Hospital, Carretera de Canyet, s\/n, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/B978-0-444-64034-5.00020-1","article-title":"Brain arteriovenous malformations","volume":"Volume 176","author":"Rutledge","year":"2021","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1136\/neurintsurg-2021-018181","article-title":"Venous tortuosity as a novel biomarker of rupture risk 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