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Stimulation of post\u2010stroke angiogenesis using vascular endothelial growth factor (VEGF)\u2010A is associated with an increased risk of vascular destabilization, leading to life\u2010threatening complications. The non\u2010mammalian VEGF\u2010A homolog, VEGF\u2010E, stimulates stable cutaneous vascularization and promotes wound healing. Herein, we posit that VEGF\u2010E represents a potential mediator of reparative revascularization after ischemic stroke. C57BL6\/J wildtype mice were subjected to experimental stroke, and VEGF\u2010E or VEGF\u2010A were intranasally delivered during the subacute phase. Our results indicate that VEGF\u2010E improves neurological recovery and increases vascular density without compromising permeability, more efficiently than VEGF\u2010A. We show that VEGF\u2010E\u2010mediated revascularization correlates with normal restoration of brain perfusion, whereas VEGF\u2010A induces cerebral hyperperfusion, indicative of vascular dysfunction. Furthermore, VEGF\u2010E reduces microvascular stalls, increases the density of angiogenic vasculature, and improves the interaction of brain endothelial cell with pericytes, which is critical for vascular stabilization. Using cell\u2010based assays, we demonstrate that stimulation of brain endothelial cells with VEGF\u2010E, but not with VEGF\u2010A, increases the expression of platelet\u2010derived growth factor (PDGF)\u2010D, a potent ligand of PDGFR\u03b2 that plays critical roles in regulating the survival and functions of perivascular cells, including pericytes. These effects are associated with activation of extracellular signal\u2010regulated kinase (ERK)1\/2 and P38 mitogen\u2010activated protein kinase (MAPK). Finally, we confirm that the secretome of VEGF\u2010E\u2010stimulated brain endothelial cells ameliorates pericyte migration required for vascular recruitment. Our study indicates that VEGF\u2010E promotes a stable and functional revascularization after ischemic stroke, outlining its promises for therapeutic purposes.<\/jats:p>","DOI":"10.1111\/ejn.70114","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T07:04:45Z","timestamp":1745564685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["VEGF\u2010E Attenuates Injury After Ischemic Stroke by Promoting Reparative Revascularization"],"prefix":"10.1111","volume":"61","author":[{"given":"Romain","family":"Menet","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neuroscience, Faculty of Medicine Universit\u00e9 Laval  Quebec City Quebec Canada"},{"name":"Neuroscience Axis Research Center of CHU de Qu\u00e9bec \u2010 Universit\u00e9 Laval  Quebec City Quebec 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