Angiophagy

Cell viability in the brain is critically dependent on uninterrupted blood flow through the microvasculature. However, microvessels, because of their small diameter and low-flow velocity, are prone to occlusion by blood clots, fragments of atheromatous plaques, or other circulating debris. Furthermore, microvascular occlusions can occur after large-vessel thrombosis because of blood stasis or due to clot fragmentation and distal microembolization. Microvascular occlusion could thus be a frequent phenomenon throughout life that may play important roles in the pathogenesis of cerebral ischemia and reperfusion, age-related vascular cognitive impairment, and cognitive decline after surgical procedures, such as coronary artery bypass graft.Given the propensity of microvessels to occlusion, it is likely that robust mechanisms have evolved to ensure microvascular patency. The main mechanism that prevents microvascular occlusion is constituted by the combined effects of the fibrinolytic system and hemodynamic pressure, which lead to embolus dissolution and washout. However, the fibrinolytic system is limited to breaking down fibrin-based blood clots and is unable to disrupt other materials, such as calcium and cholesterol crystals and cell debris, which are present in complex thrombi and may occlude microvessels throughout life.Using an experimental mouse model of internal carotid embolization with fluorescently labeled microemboli (10–60 µm), we were able to study the outcome of individual microvascular occlusions in the mouse brain. We tracked individual microvessels using high-resolution confocal imaging in histological brain preparations and by time-lapse 2 photon microscopy of the meninges and superficial cortex in living mice. Using these methods, we recently found a novel mechanism of microvascular recanalization, which we termed “angiophagy.” This mechanism involves the engulfment of emboli by the endothelium followed by their translocation through the vessel wall into the perivascular space.Angiophagy is a robust mechanism that leads to blood flow reestablishment within hours of the embolus extrusion.1 Embolus extravasation …