Abstract A017: Intra-Arterial IL-6 Activates Microglia-Driven VEGF Repair to Improve Stroke Recovery

Even after successful reperfusion, most stroke patients remain disabled, highlighting the urgent need for therapies that promote true repair. Angiogenesis is a critical yet underexploited process in recovery. Here we report the first demonstration of a monocyte–interleukin-6 (IL-6)–microglia axis that induces a pro-angiogenic microglial switch and drives VEGF-mediated repair. We define this pathway in a mouse stroke model, confirm repair-associated microglia (RAMs) in human tissue, validate it in an ex vivo ischemia model, and extend these findings to an endovascular therapy that reduced stroke volume, enhanced angiogenesis, and improved recovery in vivo. In a transient middle cerebral artery occlusion (MCAo) model, VEGF+ RAMs emerged during the subacute phase (days 3–7). Flow cytometry and histology showed this transition required infiltrating CCR2+ monocytes. CCR2 deletion blocked the VEGF switch, reduced peri-infarct microvascular density by 44.7% ± 6.3 (p