Endothelial cells, brain capillary microvessel

Fig. 2 Immunodetection of brain microvessels following injury of blood-brain barrier. Consequences of intra-caudate-putamen (CP) injection of HIV-1 gpl 20 (500 ng) on rat brain endothelial cells and capillaries after 1 h survival, (a) The reduction in the number of microvessels is shown by the decrease in the number of RECA-1-positive structures, (b) Cryostat sections immunostained for CD31 and processed for the TUNEL assay. Some of the endothelial cells, positive for CD31, are also TUNEL positive and thus apoptoBc arww. Scale bars=ADD pm (modified from [105])...

MDCK (Madin-Darby canine kidney) cells are derived from distal tubules, whereas LLC-PKi are from proximal tubes. b BMEC (brain microvessel endothelial cells) are isolated from capillaries. BPAEC (bovine pulmonary artery endothelial cells), BAEC (bovine aortic endothelial cells), and HUVEC (human umbilical vein endothelial cells) are large vessel endothelia. 

The cerebral endothelial cells of the blood-brain barrier originate from the middle germinal sheet of the embryo, the mesoderm [17]. Concomitant with migration and proliferation of capillary endothelial cells during formation of the cerebral vascular network occurs the imprinting of the cells. Thereby, induction by the cellular surrounding plays an important role [18-21], The relevance of the cellular environment for the development of the barrier function of cerebral microvessels was first demonstrated by Stewart and Wiley [22], who transplanted embryonic brain tissue of a quail into embryonic gut tissue of chicken and vice versa. The cerebral transplant was vascularized by intestinal vessels, in which properties of the blood-brain barrier had been induced. In transplanted brain vessels, however, no characteristics of a barrier could be demonstrated, due to the lack of a neuronal environment. These results indicated that the cerebral microvessels are of extraneuronal origin, with properties that are induced by the cellular environment. In addition, brain tissue has the capability to induce blood-brain barrier characteristics also in noncerebral vascular tissue [23],... 

The rather time- and cost-expensive preparation of primary brain microvessel endothelial cells, as well as the limited number of experiments which can be performed with intact brain capillaries, has led to an attempt to predict the blood-brain barrier permeability of new chemical entities in silico. Artificial neural networks have been developed to predict the ratios of the steady-state concentrations of drugs in the brain to those of the blood from their structural parameters [117, 118]. A summary of the current efforts is given in Chap. 25. Quantitative structure-property relationship models based on in vivo blood-brain permeation data and systematic variable selection methods led to success rates of prediction of over 80% for barrier permeant and nonper-meant compounds, thus offering a tool for virtual screening of substances of interest [119]. 

Most electron microscopic studies of BBB endothelial cells suggest the presence of relatively few observable endocytic vesicles in the cytoplasm of these cells compared with other endothelia. For example, the BBB contains only a fifth to a sixth of the endocytic profiles seen in muscle capillary endothelia [54], although they may increase to comparable levels with inflammation of the BBB [55]. However, when a comparison is made of the ability of capillary endothelia in a variety of different tissues to trancytose protein, there is a very poor correlation between the protein permeability of a microvessel and the number of observable endocytic profiles [54]. Brain capillary endothelia are very thin cells, the luminal and ablum-inal membranes only being separated by some 500 nm or less (5000 A), and caveoli are 50-80 nm in diameter and thus the events of transcytosis may be difficult to capture within the cell using conventional electron microscopical techniques. 

Thole, M., et al. 2002. Uptake of cationized albumin coupled liposomes by cultured porcine brain microvessel endothelial cells and intact brain capillaries. J Drug Target 10 337. 

The blood-brain barrier is a biochemical as well as a physical barrier. Brain endothelial cells create an enzymatic barrier composed of secreted proteases and nucleotidases, as well as intracellular metabolizing enzymes such as cytochrome P-450. Furthermore, y-glutamyl transpeptidase, alkaline phosphatase, and aromatic acid decarboxylase are more prevalent in cerebral microvessels than in nonneuronal capillaries. The efflux transporter P-glycoprotein and other extrusion pumps are present on the membrane surface of endothelial cells, juxtaposed toward the interior of the capillary. Furthermore, CNS endothelial cells display a net negative charge at the interior of the capillaries and at the basement membrane. This provides an additional selective mechanism by impeding passage of anionic molecules across the membrane. 

Figure9.12 (a) Cerebral capillary covered with astrocyte end-feet, (b) Cross section of a brain microvessel formed by endothelial cells, pericytes, and astrocyte end-feet (from Ref. [104]).

The blood-brain barrier (BBB) is a selective barrier formed by endothelial cells that hne the cerebral microvessels and is present in all vertebrate animals [ 1], It consists of a network of capillaries in the human brain with an approximately total length of 600 km and an average distance of 40 pm from each capillary [2]. 

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