{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:27:29Z","timestamp":1791412049743,"version":"4.3.3"},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T00:00:00Z","timestamp":1608508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Vasculotide (VT), an angiopoietin\u20101 mimetic peptide, exerts neuroprotective effects in type one diabetic (T1DM) rats subjected to ischemic stroke. In this study, we investigated whether delayed VT treatment improves long\u2010term neurological outcome after stroke in T1DM rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Wistar rats were induced with T1DM, subjected to middle cerebral artery occlusion (MCAo) model of stroke, and treated with PBS (control), 2\u00a0\u00b5g\/kg VT, 3\u00a0\u00b5g\/kg VT, or 5.5\u00a0\u00b5g\/kg VT. VT treatment was initiated at 24\u00a0h after stroke and administered daily (i.p) for 14\u00a0days. We evaluated neurological function, lesion volume, vascular and white matter remodeling, and inflammation in the ischemic brain. In vitro, we evaluated the effects of VT on endothelial cell capillary tube formation and inflammatory responses of primary cortical neurons (PCN) and macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment of T1DM\u2010stroke with 3\u00a0\u00b5g\/kg VT but not 2\u00a0\u00b5g\/kg or 5.5\u00a0\u00b5g\/kg significantly improves neurological function and decreases infarct volume and cell death compared to control T1DM\u2010stroke rats. Thus, 3\u00a0\u00b5g\/kg VT dose was employed in all subsequent in vivo analysis. VT treatment significantly increases axon and myelin density, decreases demyelination, decreases white matter injury, increases number of oligodendrocytes, and increases vascular density in the ischemic border zone of T1DM stroke rats. VT treatment significantly decreases MMP9 expression and decreases the number of M1 macrophages in the ischemic brain of T1DM\u2010stroke rats. In vitro, VT treatment significantly decreases endothelial cell death and decreases MCP\u20101, endothelin\u20101, and VEGF expression under high glucose (HG) and ischemic conditions and significantly increases capillary tube formation under HG conditions when compared to non\u2010treated control group. VT treatment significantly decreases inflammatory factor expression such as MMP9 and MCP\u20101 in macrophages subjected to LPS activation and significantly decreases IL\u20101\u03b2 and MMP9 expression in PCN subjected to ischemia under HG conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Delayed VT treatment (24\u00a0h after stroke) significantly improves neurological function, promotes vascular and white matter remodeling, and decreases inflammation in the ischemic brain after stroke in T1DM rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13541","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T23:03:16Z","timestamp":1608591796000},"page":"48-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Treatment with an Angiopoietin\u20101 mimetic peptide promotes neurological recovery after stroke in diabetic 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