{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:09:27Z","timestamp":1792037367831,"version":"4.4.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T00:00:00Z","timestamp":1734393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS119477"],"award-info":[{"award-number":["NS119477"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disease and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Hypoxia triggers blood\u2013brain barrier disruption and a strong microglial activation response around leaky cerebral blood vessels. These events are greatly amplified in aged mice which is translationally relevant because aged patients are far more likely to suffer hypoxic events from heart or lung disease, and because of the pathogenic role of blood\u2013brain barrier breakdown in vascular dementia. Importantly, it is currently unclear if disrupted cerebral blood vessels spontaneously repair and if they do, whether surrounding microglia deactivates. In this study, we addressed these questions by exposing aged (20 months old) mice to chronic mild hypoxia (8% O2) for 7 days and then returned them to normoxic conditions for 7 or 14 days, before evaluating blood\u2013brain barrier disruption and microglial activation at the different timepoints. Seven days chronic mild hypoxia triggered marked blood\u2013brain barrier disruption, as measured by extravascular leak of fibrinogen and red blood cells, which led to enhanced microglial activation, as measured by Mac-1 and CD68 levels. Interestingly, while return to normoxia promoted spontaneous repair of damaged blood vessels, the surrounding microglia remained persistently activated and were slow to deactivate. Chronic mild hypoxia also triggered neuronal loss that resulted in irreversible cognitive decline as measured by the novel object recognition test. Taken together, these findings describe an important disconnect between vascular repair and microglial deactivation in aged mice, which likely contributes to prolonged neuroinflammation. As hypoxia occurs in many age-related conditions, our data have important implications for the pathogenic role of hypoxia in the induction and progression of vascular dementia.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae456","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T16:07:41Z","timestamp":1734451661000},"source":"Crossref","is-referenced-by-count":13,"title":["Blood\u2013brain barrier disruption and microglial activation during hypoxia and post-hypoxic recovery in aged mice"],"prefix":"10.1093","volume":"7","author":[{"given":"Arjun","family":"Sapkota","sequence":"first","affiliation":[{"name":"San Diego Biomedical Research Institute , San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-3864","authenticated-orcid":false,"given":"Sebok K","family":"Halder","sequence":"additional","affiliation":[{"name":"San Diego Biomedical Research Institute , San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Milner","sequence":"additional","affiliation":[{"name":"San Diego Biomedical Research Institute , San Diego, CA 92121 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,17]]},"reference":[{"key":"2024123013263885700_fcae456-B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The blood-brain barrier: An overview. 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