{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T19:30:07Z","timestamp":1784143807249,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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\/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":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Senescence has been recently described in brain cells following ischemic stroke. The potential of targeting senescence as an effective therapeutic approach in the treatment of ischemic stroke requires further investigation. This study evaluated the effects of the senolytic drug navitoclax after experimental ischemic stroke. Methods: Navitoclax was injected into male young Wistar rats at doses of 10 and 30 mg\/kg (i.p.). to evaluate its pharmacokinetics, cerebral levels and potential to cause thrombocytopenia. Subsequently, a second group of rats underwent 60 min of transient middle cerebral artery occlusion (tMCAO). Navitoclax (10 mg\/kg, i.p.) or vehicle was injected every other day between days 3 and 13 after tMCAO. Neurofunctional performance, infarct size, and senescence markers were assessed on day 14. Results: Navitoclax (10 mg\/kg) administration resulted in a maximum plasma concentration of 0.702 mg\/L and half-life of 11.33 h. Additionally, a brain concentration of 0.04 \u00b1 0.02 \u00b5g\/g was detected. Moderate thrombocytopenia was induced by 10 mg\/kg, and to a greater extent by 30 mg\/kg. Navitoclax (6 \u00d7 10 mg\/kg) improved neurofunctional impairment, as indicated by significant decrease by 66% in the total time for the tape removal test, and significantly reduced infarct area by 52% when compared to vehicle. Moreover, navitoclax significantly reduced levels of SA-\u03b2-gal (by 80%), lipofuscin (by 91%), and Checkpoint kinase 2 (Chk2; by 69%) in the ischemic hemisphere. Conclusions: Navitoclax protects the brain after ischemic stroke by improving neurofunctional outcome and reducing infarct size, which is associated with reducing senescence markers. Although moderate thrombocytopenia warrants caution, targeting senescence emerges as a promising therapeutic strategy for ischemic stroke.<\/jats:p>","DOI":"10.3390\/ph19030431","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T11:05:44Z","timestamp":1772795144000},"page":"431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Senolytic Drug Navitoclax Protects the Brain After Experimental Ischemic Stroke"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0697-6519","authenticated-orcid":false,"given":"Dianoush","family":"Falahatgaroshibi","sequence":"first","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"},{"name":"Departamento de Biotecnolog\u00eda, Universidad Polit\u00e9cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-9171","authenticated-orcid":false,"given":"J\u00falia","family":"Baixauli-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C.","family":"Burguete","sequence":"additional","affiliation":[{"name":"Unidad Mixta de Investigaci\u00f3n Cerebrovascular, Instituto de Investigaci\u00f3n Sanitaria 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, 46026 Valencia, Spain"},{"name":"Departamento de Fisioterapia, Universidad de Valencia, 46010 Valencia, 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, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 E.","family":"Peris","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia y Tecnolog\u00eda Farmac\u00e9utica y Parasitolog\u00eda, Universidad de Valencia, 46100 Burjassot, 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, 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":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/17474930241308142","article-title":"World Stroke Organization: Global Stroke Fact Sheet 2025","volume":"20","author":"Feigin","year":"2025","journal-title":"Int. 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