Transport of proteins across normal cerebral arterioles

Abstract

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 p, 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 endothelid 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 endothelid junctions, was also transported across the same s e p e n t s 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.

Effects of Bradykinin on Permeability and Diameter of Pial Vessels In vivo

“…A similar vasomotor behavior of the extra-and intraparenchymal cerebral vessels has often been shown lfor review see Kuschinsky and Wahl (1978)]. Evidence for the impermeability of pial vessels to intravascular material used as barrier indicators, such as Evans blue, peroxidase, Na + fluorescein, FITC-dextran, and FITC-albumin, has been provided by several groups (Rapoport et al, 1972;Westergaard and Brightman, 1973;Hultstrom et aI., 1983;Wahl et aI., 1984).…”

The Blood–Brain Barrier

“…CNS ECs are held together by tight junctions (TJs), which greatly limit the paracellular flux of solutes (Reese and Karnovsky 1967;Brightman and Reese 1969;Westergaard and Brightman 1973). CNS ECs undergo extremely low rates of transcytosis as compared with peripheral ECs, which greatly restricts the vesicle-mediated transcellular movement of solutes (Coomber and Stewart 1985).…”

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

“…However, the free entry of drugs from the blood into the brain is restricted by the presence of two barriers, the blood-brain barrier (BBB) and the blood-cerebrospinal¯uid (CSF) barrier. The BBB is found at the level of the cerebral capillary endothelium and is associated with the presence of tight junctions, metabolic enzymes, and the lack of intracellular vesicles and endothelial fenestrae (Bertler et al, 1966;Reese & Karnovsky, 1967;Brightman & Reese, 1969;Westergaard & Brightman, 1973;Shivers et al, 1984;Watson et al, 1991). The barrier between blood and CSF is located at the tight junctions of the choroid plexus epithelium and the dura-arachnoid boundary (Brightman & Reese, 1969;Nabeshima et al, 1975;Smith & Shine, 1992).…”