Clearing Your Head by Translocation of Emboli

The investigators used transcranial two-photon microscopy of the cerebral microvasculature to evaluate the fate of fluorescent fibrin clots, cholesterol emboli, and microspheres infused through the internal carotid arteries of mice. Mice expressing Tie2-green fluorescent protein were used in these studies to visualize the endothelium following infusion of fluorescent emboli. The investigators found that emboli that were not lysed within the first few hours following infusion were extravasated from the vessel over a two- to seven-day period. Electron microscopy of tissue samples from these mice confirmed that the emboli had been extruded into the surrounding tissue. An open luminal space completely surrounded by an endothelial layer was observed next to the extravasated emboli, consistent with the observation that blood flow is restored after translocation. Time-lapse imaging demonstrated how the endothelium generated the proto-lumen. Endothelial membrane projections formed around the emboli. The new endothelium grew all the way around the emboli to create the proto-lumen (Figure). The original endothelium concurrently underwent retraction, enabling the extravasation of emboli into the perivascular parenchyma. Inhibitors of matrix metalloproteinases interrupted this process, suggesting that proteases participate in the remodeling of the endothelium and are required for embolic extravasation. The authors also compared emboli extravasation in younger mice to that of older mice. They found that the rate of emboli extravasation is substantially slower in older mice. In addition, the older mice suffered increased synaptic injury and death following infusion of emboli.