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In this study, we investigated the long-term effects of clinically relevant treatment regimens with cyclophosphamide (CP) and vincristine (VIN) on cerebrovascular cellular senescence, associated molecular signatures, and downstream functional outcomes, including disruption of blood\u2013brain barrier (BBB) integrity in a mouse model. Our results showed that CP induces a persistent cerebrovascular endothelial phenotype characterized by increased cellular senescence, upregulation of mRNA expression of DNA damage checkpoint regulators, and concomitant downregulation of key DNA repair genes. BBB integrity was preserved after CP treatment for larger molecular tracers (40\u00a0kDa and 3\u00a0kDa) but exhibited increased permeability to small tracers (0.3\u00a0kDa), measured by in vivo two-photon microscopy, indicating a subtle yet persistent disruption of barrier function. In contrast, VIN elicited a markedly attenuated and heterogeneous transcriptional response and did not produce detectable BBB impairment, underscoring agent-specific cerebrovascular effects of chemotherapy. Collectively, these findings suggest that chemotherapy induces a persistent cerebrovascular injury phenotype with features resembling vascular aging and reduced vascular resilience, providing a potential mechanistic link between systemic cancer therapy and long-term adverse effects on brain health.<\/jats:p>","DOI":"10.1007\/s11357-026-02270-3","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T21:52:45Z","timestamp":1777585965000},"page":"7407-7422","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long-term cerebrovascular effects of cyclophosphamide and vincristine: endothelial senescence, impaired DNA repair signaling, and blood\u2013brain barrier dysfunction"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2067-753X","authenticated-orcid":false,"given":"Dorina","family":"Nagy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana Vali","family":"Kordestan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Patai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Gulej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siva Sai","family":"Chandragiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavendra Y.","family":"Nagaraja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santny","family":"Shanmugarama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoba","family":"Ekambaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeka","family":"Kristof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Nagykaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parikshat","family":"Sirpal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Yabluchanskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl E.","family":"Balsara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene Y.","family":"McNall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Ungvari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Csiszar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"2270_CR1","doi-asserted-by":"publisher","unstructured":"Nagy D, Chandragiri SS, Vali Kordestan K, Ekambaram S, Nagykaldi M, Patai R, Gulej R, Nagaraja RY, Brunner E, Kristof R, et al. 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