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J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>\n                    Diabetes increases the risk of vascular contributions to cognitive impairment and dementia (VCID). Using a microemboli (ME) model, we found that diabetic rats experience more severe white matter damage and progressive cognitive decline than controls. Moreover, the restoration of endothelial function before ME injection prevents VCID in diabetes. Given that diabetes mediates early endothelial dysfunction, activates the endothelin (ET) system, and the post-mortem brain (b) ET-1 levels correlate with tissue hypoxia in dementia patients, this study investigated the relationship between ET system, hypoxia, and neuroinflammation in this clinically relevant VCID model. While there were no ME-mediated changes or differences between control and diabetic groups in plasma and bET-1 levels, bET-1 levels correlated with hypoxia markers.\u00a0ET\n                    <jats:sub>A<\/jats:sub>\n                    R expression was reduced by the ISMN (75\u2009mg\/kg\/day) and cilostazol (60\u2009mg\/kg\/day) treatment. On the other hand, ET\n                    <jats:sub>B<\/jats:sub>\n                    R expression was lower in the sham diabetic group compared to the sham controls, and ME injection did not have further effect. The treatment restored ET\n                    <jats:sub>B<\/jats:sub>\n                    R expression to comparable levels in the control sham group. These findings suggest a link between the ET system, hypoxia, and neuroinflammation in diabetic VCID. Modulating the ET system may be a viable therapeutic strategy to improve vascular function and prevent VCID.\n                  <\/jats:p>","DOI":"10.1139\/cjpp-2025-0350","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:32:46Z","timestamp":1772659966000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microemboli model of vascular cognitive impairment\/dementia (VCID) presents with long-term brain tissue hypoxia: relevance to the endothelin (ET) system"],"prefix":"10.1139","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-018X","authenticated-orcid":false,"given":"Weiguo","family":"Li","sequence":"first","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eda","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jazlyn","family":"Edwards","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Li","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marice K.","family":"McCrorey","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen M.","family":"Butler","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina","place":["Charleston, USA"]},{"name":"Ralph H. 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