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The white matter, which is essential for neuronal information processing and integration, is nourished by a network of capillaries and is vulnerable to chronic hypoperfusion. Here, we show that metformin, a widely used drug for the treatment of type 2 diabetes, alleviates the white matter damage and improves cognitive impairment in a mouse model of VCID established by bilateral carotid artery stenosis (BCAS)-induced chronic hypoperfusion. Mechanistically, metformin restores the dysfunctions of oligodendrocyte precursor cells (OPCs) under hypoxia. Metformin up-regulates prolyl hydroxylases 2 via activating the AMP-activated protein kinase pathway, leading to hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) degradation in OPCs. These findings suggest that metformin may have a promising therapeutic role in alleviating cognitive abnormalities by ameliorating white matter damage of VCID.<\/jats:p>","DOI":"10.1177\/0271678x231175189","type":"journal-article","created":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T01:56:16Z","timestamp":1683942976000},"page":"78-94","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Metformin attenuates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion"],"prefix":"10.1177","volume":"43","author":[{"given":"Yixi","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 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