{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:23:19Z","timestamp":1793881399367,"version":"4.7.0"},"reference-count":38,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T00:00:00Z","timestamp":1424822400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive\/stroke prone rats (SHR\/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood\u2013brain barrier (BBB) disruption. Twelve-week-old SHR\/SP had UCAO\/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO\/JPD, WM showed a significant increase in hypoxia inducible factor-1\u03b1 (HIF-1\u03b1), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO\/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg\/kg intraperitoeally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life.<\/jats:p>","DOI":"10.1038\/jcbfm.2015.21","type":"journal-article","created":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T03:54:48Z","timestamp":1424836488000},"page":"1145-1153","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":116,"title":["Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR\/SP"],"prefix":"10.1177","volume":"35","author":[{"given":"Fakhreya Y","family":"Jalal","sequence":"first","affiliation":[{"name":"Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"},{"name":"Present address: Department of Pharmacology and Therapeutics, United Arab Emirates University, College of Medicine and Health Sciences, Al-Ain, UAE."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey F","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Roitbak","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"},{"name":"Department 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