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However, because pharmacological agents specifically for WMI are lacking, novel therapeutic strategies need to be explored. It is recently found that adaptive myelination is required for homeostatic control of brain functions. In this study, adaptive myelination\u2010related strategies are applied\u00a0to explore the treatment for ischemic\u00a0WMI\u2010related cognitive dysfunction. Here, bilateral carotid artery stenosis (BCAS) is used to model ischemic WMI\u2010related cognitive impairment and uncover that optogenetic and chemogenetic activation of glutamatergic neurons in the medial prefrontal cortex (mPFC) promote the differentiation of oligodendrocyte precursor cells (OPCs) in the corpus callosum, leading to improvements in myelin repair and working memory. Mechanistically, these neuromodulatory techniques exert a therapeutic effect by inducing the secretion of Wnt2 from activated neuronal axons, which acts on oligodendrocyte precursor cells and drives oligodendrogenesis and myelination. Thus, this study suggests that neuromodulation is a promising strategy for directing myelin repair and cognitive recovery through adaptive myelination in the context of ischemic WMI.<\/jats:p>","DOI":"10.1002\/advs.202202976","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:55:39Z","timestamp":1671411339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Optogenetic Stimulation of mPFC Alleviates White Matter Injury\u2010Related Cognitive Decline after Chronic Ischemia through Adaptive Myelination"],"prefix":"10.1002","volume":"10","author":[{"given":"Shiji","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurology Drum Tower Hospital Medical School and The State Key Laboratory of Pharmaceutical Biotechnology Institute of Translational Medicine for Brain Critical Diseases Nanjing University  Nanjing 210008 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