Vesicular transport of horseradish peroxidase from brain to blood in segments of the cerebral microvasculature in adult mice.

The transfer of protein from the cerebral ventricles to the parenchymal bloodstream in mice was studied by electron microscopy. After perfusion with the protein tracer horseradish peroxidase (HRP; M.W. approx. 40,000) through the cerebral ventricles, the tracer penetrated the ependymal lining of the ventricles and was found in the extracellular space of the neuropil close to the ependyma. HRP was also seen in the vascular basement membrane and in endothelial vesicles opening at the abluminal endothelial surface, or situated within the endothelial cells in segments of the microvasculature (mostly small arterioles). In some of these segments HRP was also seen on the luminal surface of the endothelia and in surface-connected vesicles. The junctions connecting adjacent endothelial cells were never penetrated by HRP. It is concluded that vesicular transport of HRP across the endothelium of the cerebral microvasculature represents a possible mechanism for protein removal from brain extracellular space.