{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:27:35Z","timestamp":1792009655210,"version":"4.4.0"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Type 2 diabetes mellitus (T2DM) is a major comorbidity that exacerbates ischemic brain injury and worsens functional outcome after stroke. T2DM is known to aggravate white matter (WM) impairment, but the underlying mechanism is not completely understood. This study was designed to test the hypothesis that T2DM impedes poststroke WM recovery by suppressing both oligodendrogenesis and beneficial microglia\/macrophage responses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Permanent distal middle cerebral artery occlusion was performed in wild-type, homozygous diabetic db\/db, and heterozygous db\/+ mice. The adhesive removal, open field, and Morris water maze tests were used to assess neurobehavioral outcomes. Neuronal tissue loss, WM damage, oligodendrogenesis, and microglia\/macrophage responses were evaluated up to 35 days after stroke. The functional integrity of WM was measured by electrophysiology. Primary microglia-oligodendrocyte cocultures were used for additional mechanistic studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>T2DM exacerbated structural damage and impaired conduction of compound action potentials in WM 35 days after stroke. The deterioration in WM integrity correlated with poor sensorimotor performance. Furthermore, T2DM impaired the proliferation of oligodendrocyte precursor cells and the generation of new myelinating oligodendrocytes. T2DM also promoted a shift of microglia\/macrophage phenotype toward the proinflammatory modality. Coculture studies confirmed that microglia\/macrophage polarization toward the proinflammatory phenotype under high glucose conditions suppressed oligodendrocyte precursor cell differentiation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Deterioration of WM integrity and impairments in oligodendrogenesis after stroke are associated with poor long-term functional outcomes in experimental diabetes mellitus. High glucose concentrations may shift microglia\/macrophage polarization toward a proinflammatory phenotype, significantly impairing oligodendrocyte precursor cell differentiation and WM repair.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.118.021452","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T18:04:17Z","timestamp":1537812257000},"page":"2453-2463","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":87,"title":["Diabetes Mellitus Impairs White Matter Repair and Long-Term Functional Deficits After Cerebral Ischemia"],"prefix":"10.1161","volume":"49","author":[{"given":"Shubei","family":"Ma","sequence":"first","affiliation":[{"name":"From the Institute of Cerebrovascular Disease Research and Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China (S.M., Y.L.)"},{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., J.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., J.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Wang","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., J.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Dai","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., J.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Healthcare System, PA (F.X., X.H., J.C.)"},{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., J.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Gao","sequence":"additional","affiliation":[{"name":"Pittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh School of Medicine, PA (S.M., J.W., Y.W., X.D., F.X., X.G., J.J., N.X., X.H., 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