ABSTRACT NUMBER: ESOC2026A2233 MICROVASCULAR RECANALIZATION BY EMBOLUS EXTRAVASATION IN A RODENT MODEL OF SILENT BRAIN INFARCTS

Abstract Background and aims Micro-embolus lodging in the cerebral micro-circulation prior and during an acute ischemic stroke may contribute to the lack of microvascular reperfusion after treatment and is a potential factor in poor patient outcome. Micro-emboli can be cleared by endogenous fibrinolysis or by the lesser-known process of angiophagy, where occluding particles are extravasated via endothelial transmigration. However, the mechanisms of embolus extravasation remain poorly understood. A better understanding of embolus clearance may reveal new approaches to improve reperfusion after stroke. We investigated the mechanisms of angiophagy in a rodent model of silent brain infarcts. Methods We injected fluorescent microparticles (10 μm) whose lodging and extravasation were followed in vivo using two-photon microscopy for up to 28 days. In addition, cellular mechanisms of angiophagy were studied in an in vitro blood-brain barrier (BBB) model. Results Two-photon imaging observations showed reduced blood flow, transient BBB leakage, vascular diameter changes, and angiophagy of the microparticle. Vessels with a diameter of approximately 5 to 7 μm substantially expand distally from the microparticles, allowing 10 μm particles to slowly pass through the capillary network and extravasate within a few days. In vitro, actin remodeling drives endothelial engulfment and pore formation around microparticles, accompanied by increased VE-cadherin and CD31 expression Conclusions We found evidence for incredible plasticity of the cerebral microvasculature, allowing 1) local, active widening preceding the movement of microparticles along the capillary network and 2) removal of relatively large particles through the microvascular wall via angiophagy. Both processes could be important endogenous safety mechanisms to restore local perfusion. Conflict of interest The authors have nothing to disclose