{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:36:37Z","timestamp":1760060197033,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disease and Stroke (NINDS)","award":["NS136861"],"award-info":[{"award-number":["NS136861"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Blood\u2013brain barrier (BBB) deterioration with increasing age is an important factor contributing to vascular dementia. Previous studies show that endothelial nitric oxide synthase (eNOS) facilitates vascular endothelial growth factor-mediated angiogenesis and increased vascular permeability. In contrast, recent work has shown that aged hemi-deficient hemizygous eNOS+\/\u2212 mice manifest BBB disruption in association with increased incidence of thromboembolic events in the brain. To unravel whether eNOS contributes to or protects against hypoxia-induced cerebrovascular damage, we compared chronic mild hypoxia (CMH)-induced cerebrovascular angiogenic remodeling and BBB breakdown in aged (20 months old) eNOS+\/\u2212 and wild-type (WT) mice. This revealed that CMH strongly enhanced eNOS expression in cerebral blood vessels with much lower levels in eNOS+\/\u2212 mice. eNOS hemi-deficiency resulted in greater CMH-induced BBB disruption, but unexpectedly, had no effect on endothelial proliferation. eNOS+\/\u2212 mice also displayed enhanced endothelial expression of the endothelial activation markers MECA-32, VCAM-1, and \u03b23 integrin in cerebral blood vessels, indicating greater vascular inflammation, and this correlated with increased levels of microglial activation and demyelination. Taken together, our results support the concept that eNOS plays an important protective function in the aged brain by suppressing endothelial activation and maintaining cerebrovascular health.<\/jats:p>","DOI":"10.3390\/ijms26167902","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T16:09:55Z","timestamp":1755274195000},"page":"7902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia"],"prefix":"10.3390","volume":"26","author":[{"given":"Arjun","family":"Sapkota","sequence":"first","affiliation":[{"name":"San Diego Biomedical Research Institute, 3525 John Hopkins Court, Suite 200, San Diego, CA 92121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, 3525 John Hopkins Court, Suite 200, San Diego, CA 92121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9976-0939","authenticated-orcid":false,"given":"Saifudeen","family":"Ismael","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Clinical Neuroscience Research Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-9553","authenticated-orcid":false,"given":"Gregory J.","family":"Bix","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Clinical Neuroscience Research Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA"},{"name":"Department of Neurology, School of Medicine, Tulane University, New Orleans, LA 70112, USA"},{"name":"Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA"},{"name":"School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70122, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Milner","sequence":"additional","affiliation":[{"name":"San Diego Biomedical Research Institute, 3525 John Hopkins Court, Suite 200, San Diego, CA 92121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","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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