{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:05:37Z","timestamp":1789646737003,"version":"4.0.0"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2020-119603RB-I00"],"award-info":[{"award-number":["PID2020-119603RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RD21\/0006\/0014"],"award-info":[{"award-number":["RD21\/0006\/0014"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["CIAICO\/2022\/248"],"award-info":[{"award-number":["CIAICO\/2022\/248"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PID2020-119603RB-I00"],"award-info":[{"award-number":["PID2020-119603RB-I00"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD21\/0006\/0014"],"award-info":[{"award-number":["RD21\/0006\/0014"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIAICO\/2022\/248"],"award-info":[{"award-number":["CIAICO\/2022\/248"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016386","name":"Conselleria de Innovaci\u00f3n, Universidades, Ciencia y Sociedad Digital","doi-asserted-by":"publisher","award":["PID2020-119603RB-I00"],"award-info":[{"award-number":["PID2020-119603RB-I00"]}],"id":[{"id":"10.13039\/501100016386","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016386","name":"Conselleria de Innovaci\u00f3n, Universidades, Ciencia y Sociedad Digital","doi-asserted-by":"publisher","award":["RD21\/0006\/0014"],"award-info":[{"award-number":["RD21\/0006\/0014"]}],"id":[{"id":"10.13039\/501100016386","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016386","name":"Conselleria de Innovaci\u00f3n, Universidades, Ciencia y Sociedad Digital","doi-asserted-by":"publisher","award":["CIAICO\/2022\/248"],"award-info":[{"award-number":["CIAICO\/2022\/248"]}],"id":[{"id":"10.13039\/501100016386","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent years, evidence of the existence of cellular senescence in the central nervous system has accumulated. In ischemic stroke, cellular senescence has been suggested as an unidentified pathophysiological mechanism, prompting research into the neuroprotective potential of senolytic drugs. This study aims to provide spatio-temporal evidence of the existence of brain senescence following ischemic stroke and to elucidate the involved pathways and cell types. We focused on the most established markers of senescence: cell cycle arrest (p16, p21); lysosomal activity (senescence-associated \u03b2-galactosidase [SA-\u03b2-gal]); the senescence-associated secretory phenotype ([SASP]; Interleukin-6 [IL-6], Interleukin-1\u03b2 [IL-1\u03b2], Tumor necrosis factor [TNF]); and DNA\/nuclear damage (Checkpoint kinase 1 [Chk1], Checkpoint kinase 2 [Chk2], Lamin B1 [LB1]). Male Wistar rats underwent 60 min of transient middle cerebral artery occlusion, followed by 24 h and 3, 7, and 14 days of recovery. Our results show significant increases in p16 expression, particularly in neurons and microglia\/macrophages; SA-\u03b2-gal accumulation in the infarcted tissue; significant increases in SASP markers as early as 24 h after reperfusion; and significant changes in Chk1, Chk2, and LB1 at 14 days. Overall, our findings lend support to the existence of senescence after ischemic stroke in neurons and microglia\/macrophages. However, there is still room to gain further insight into the role of senescence in the pathophysiology of ischemic stroke and in the implementation of successful senolytic therapy.<\/jats:p>","DOI":"10.3390\/ijms26052364","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T09:59:17Z","timestamp":1741255157000},"page":"2364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Spatio-Temporal Characterization of Cellular Senescence Hallmarks in Experimental Ischemic Stroke"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-9171","authenticated-orcid":false,"given":"J\u00falia","family":"Baixauli-Mart\u00edn","sequence":"first","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Fisiolog\u00eda, Universidad de Valencia, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Consuelo","family":"Burguete","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Fisiolog\u00eda, Universidad de Valencia, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8282-0966","authenticated-orcid":false,"given":"Mikahela A.","family":"L\u00f3pez-Morales","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Fisioterapia, Universidad de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-4045","authenticated-orcid":false,"given":"Mar\u00eda","family":"Castell\u00f3-Ruiz","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Biolog\u00eda Celular, Biolog\u00eda Funcional y Antropolog\u00eda F\u00edsica, Universidad de Valencia, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-0481","authenticated-orcid":false,"given":"Alicia","family":"Aliena-Valero","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3458-5863","authenticated-orcid":false,"given":"Teresa","family":"Jover-Mengual","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Fisiolog\u00eda, Universidad de Valencia, 46100 Burjassot, Spain"},{"name":"The Saul R. Korey Department of Neurology and Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0697-6519","authenticated-orcid":false,"given":"Dianoush","family":"Falahatgaroshibi","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Biotecnolog\u00eda, Universidad Polit\u00e9cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n","family":"Torregrosa","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4162-6101","authenticated-orcid":false,"given":"Juan B.","family":"Salom","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Fisiolog\u00eda, Universidad de Valencia, 46100 Burjassot, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1177\/17474930211065917","article-title":"World Stroke Organization (WSO): Global Stroke Fact Sheet","volume":"17","author":"Feigin","year":"2022","journal-title":"Int. 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