Brain capillaries

In most parts of the body, substances, other than large molecular ones like proteins, are filtered from the blood into the extracellular space through gaps between endothelial cells in the capillary wall. Such gaps are much narrower, almost nonexistent, in brain capillaries and it is likely that any filtering is further reduced by the manner in which astrocytes pack around the capillaries. This constraint is known as the... 

H., Gottesman, M. M., Pastan, I., Willingham, M. C., Immunohisto-chemical localization in normal tissues of different epitopes in the multidrug transport protein PI70 evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein, J. Histochem. Cytochem. 1989, 37, 159-164. 

Fig. 15.3 D iagram showing a longitudinal cross-section of the blood-brain barrier, with the brain capillary endothelial cells sealed by the tight junctions and surrounded by pericytes and astrocyte foot processes. These cellular components of the BBB are separated by a basement membrane.

Fig. 15.5 D iagram showing some of the nutrient and drug transport processes associated with the brain capillary endothelial cells that form the BBB. Local transporters in the luminal or/and abluminal membranes are depicted as filled circles and ones whose location is more questionable or that are present at the BBB are depicted in open circles. GLUT1, LAT1, MCT1, oatp2 are present on both the luminal and abluminal membranes. This diagram shows that transport may be unidirectional or bidirectional.

The presence at the BBB of members of the multidrug resistance-associated protein (MRPs) family, whose members preferentially transport anionic compounds, is still controversial. The seven members of the MRP family belong, like P-gp, to the ATP-binding cassette (ABC) protein superfamily. Mrpl has been found at the BBB in isolated rat brain capillaries, primary cultures of brain capillary endothelial cells and in immortalized capillary endothelial cells, but not in human brain capillaries [59]. Another member, MRP2 has been found at the luminal membrane of the brain endothelial cells [60]. However, further studies are required to show that there are MRP transporters at the BBB (Figure 15.5). As for P-gp, a functional Mrpl was found in primary cultured rat astrocytes [56] and it has been shown to take part in the release of glutathione disulfide from brain astrocytes under oxidative stress [61]. 

The first gene-knockout mouse to become available was a mouse lacking detectable P-gp in the brain capillary endothelial cells. This has been used to elegantly... 

Betz AL, Firth JA, Goldstein GW. Polarity of the blood-brain barrier distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res 1980 192 17-28. 

Bertossi M, Virgintino D, Maiorano E, Occhiogrosso M, Roncali L. Ultra-structural and morphometric investigation of human brain capillaries in normal and peritumoral tissues. Ultrastruct Pathol 1997 21 41-49. 

Vorbrodt AW. Ultracytochemical characterization of anionic sites in the wall of brain capillaries. J Neurocytol 1989 18 359-368. 

Golden PL, Pardridge WM. P-glycopro-tein on astrocyte foot processes of unfixed isolated human brain capillaries. Brain Res 1999 819 143-146. 

Boado RJ. Molecular biology of brain capillaries. In Introduction to the Blood-Brain Barrier (Partridge WM, Ed.), 1st Edn. Cambridge Cambridge University Press 1998, 151-162. 

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1 91... 

Brain capillary endothelial cells and some neurons also express a Na+-dependent D-glucose symporter, SGLT1. SGLT1 (SLC5A1) was the first characterized of the large SLC5 family of Na-dependent symporters (SSSF) which transport various solutes and ions into cells [77, 78]. SGLT1 is found mainly in the intestine, trachea,... 

Zhang, Y., Schuetz, J.D., Elmquist, W.F. and Miller, D.W. (2004) Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells. Journal of Pharmacology and Experimental Therapeutics, 311, 449-455. 

Based on well established silica chemistry, the surface of silica nanomaterials can be modified to introduce a variety of functionalizations [3, 11, 118]. The toxicity of surface-modified nanomaterials is largely determined by their surface functional groups. As an example, Kreuter reported that an apolipoprotein coating on silica nanoparticles aided their endocytosis in brain capillaries through the LDL-receptor [122-124]. Overall, silica nanomaterials are low-toxicity materials, although their toxicity can be altered by surface modifications. 

Figure 17.1 Schematic cross section of a brain capillary formed by endothelial cells which are surrounded by pericytes and foot processes of astrocytes. Endothelial cells express various ABC-transport proteins at their luminal surface which significantly contribute to the barrier function.

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