{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:58:58Z","timestamp":1793944738242,"version":"4.8.0"},"reference-count":126,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Chronic cerebral hypoperfusion can lead to neuronal necrosis, trigger inflammatory responses, promote white matter damage, and ultimately result in cognitive impairment. Consequently, chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia. The myelin sheath is a critical component of white matter, and damage and repair of the white matter are closely linked to myelin sheath integrity. This article reviews the role of microglia in vascular dementia, focusing on their effects on myelin sheaths and the potential therapeutic implications. The findings suggest that ischemia and hypoxia cause disruption of the blood\u2013brain barrier and activate microglia, which may worsen blood\u2013brain barrier damage through the release of matrix-degrading enzymes. Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation. Damage to the blood\u2013brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia. Early activation of microglia is a protective response that contributes to the maintenance of blood\u2013brain barrier integrity through sensing, debris-clearing, and defensive mechanisms. However, prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype, resulting in myelin damage and cognitive impairment. Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia, as both are closely linked to cognitive decline. Although effective clinical treatments for myelin damage in the central nervous system are currently lacking, researchers are actively working to develop targeted therapies. Several drugs, including nimodipine, dopaminergic agents, simvastatin, biotin, and quetiapine, have been evaluated for clinical use in treating microglial and myelin damage. Future research will face challenges in developing targeted therapeutic strategies for vascular dementia, requiring further investigation into the timing, duration, and specific mechanisms of microglial activation, as well as the exploration of new drug combinations and additional therapeutic targets.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-01109","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:18:16Z","timestamp":1743121096000},"page":"1000-1012","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Crucial role of microglia-mediated myelin sheath damage in vascular dementia: Antecedents and consequences"],"prefix":"10.4103","volume":"21","author":[{"given":"Qi","family":"Shao","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 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