Transport of proteins across normal cerebral arterioles

Portions of certain arterioles on the surface of the brain and within it can transfer protein from blood to perivascular basement membrane. One to 50 mg of horseradish peroxidase (MW: 40,000) were injected intravenously into normal, adult mice. Three to 30 minutes later, their brains were fixed by vascular perfusion of aldehydes, incubated, and processed for electron microscopy. Segments of some cerebral arterioles, with an average diameter of 15‐30 μ, transported peroxidase. The pial arterioles were mainly situated within sulci, the parenchymal ones in the ventral part of the diencephalon and adjacent brain stem. The arteriolar segments were, commonly, bifurcations and short, straight portions. Similar vessels transferred protein in normal rats and hamsters. Neither increasing the dose of peroxidase above 10 mg nor the circulation time from 3 to 30 minutes altered the number of transferring vessels in mice. The endothelial cells were, as in cerebral capillaries, linked by tight junctions that prevented the extracellular passage of peroxidase. When peroxidase was injected 45 minutes after fixation, it did not reach the basement membrane. Moreover, ferritin, too large a molecule (MW: 900.000) to pass through these endothelial junctions, was also transported across the same segments 3 minutes after 100‐500 mg had been injected intravenously. These observations indicate that vesicular transport rather than passive, extracellular movement was the means of transferring proteins from blood to perivascular basement membrane. It is probable that serum albumin and globulins are likewise transferred in normal rodents.