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Sleep loss also induces low-grade neuroinflammation characterized by glial reactivity and blood\u2013brain barrier (BBB) dysfunction, as evidenced by BBB hyperpermeability and tight junction disassembly. Additionally, it raises molecules related to the senescence-associated secretory phenotype (SASP) in aged subjects, suggesting an increase in senescent cells. Here, we assessed the impact of sleep restriction on cellular senescence, neuroinflammation, and BBB function in the cerebral cortex and hippocampus of young male C57BL\/6 mice. Sleep restriction induced a progressive increase in BBB permeability after 3, 5, and 10\u00a0days, along with a higher expression of the astroglial marker, the glial fibrillary acidic protein (GFAP), and the expression of the C3 complement component. The pro-inflammatory cytokines tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1 beta (IL-1\u03b2), and interleukin-6 (IL-6) increased in a region-dependent form. Furthermore, the progressive increase of the senescence markers \u03b2-galactosidase and p21 observed in both brain regions was accompanied by a neurotoxic astroglial response. Our data suggest that sleep restriction promotes cellular senescence in the cerebral cortex and hippocampus of young mice.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11064-025-04510-y","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T09:36:30Z","timestamp":1755509790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Progressive Blood\u2013Brain Barrier Disruption in Sleep-Restricted Young Mice: Cellular Senescence and Neuroinflammation Crosstalk"],"prefix":"10.1007","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-2150","authenticated-orcid":false,"given":"Jessica J.","family":"Avilez-Avilez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1259-5155","authenticated-orcid":false,"given":"Jes\u00fas Enrique","family":"Garc\u00eda-Aviles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8032-806X","authenticated-orcid":false,"given":"Ricardo Jair","family":"Ram\u00edrez-Carreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6319-7770","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Salas-Venegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-1518","authenticated-orcid":false,"given":"Mara A.","family":"Guzm\u00e1n-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-7087","authenticated-orcid":false,"given":"Fernanda","family":"Medina-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-8770","authenticated-orcid":false,"given":"Mina","family":"K\u00f6nigsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6412-0461","authenticated-orcid":false,"given":"Anah\u00ed","family":"Chavarr\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-0118","authenticated-orcid":false,"given":"Beatriz","family":"G\u00f3mez-Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"issue":"5","key":"4510_CR1","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1007\/s11357-020-00235-8","volume":"42","author":"AM Mahalakshmi","year":"2020","unstructured":"Mahalakshmi AM, Ray B, Tuladhar S, Bhat A, Bishir M, Bolla SR, Yang J, Essa MM, Chidambaram SB, Guillemin GJ, Sakharkar MK (2020) Sleep, brain vascular health and ageing. 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