Brain microvessel

Dzenko KA, Andjelkovic AV, Kuziel WA, et al. The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels. J Neurosci 2001 21 9214-9223. 

Pal, D. Audus, K. L. Siahaan, T. J., Modulation of cellular adhesion in bovine brain microvessel endothelial cells by a decapeptide, Brain Res. 747, 103-113 (1997). 

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. 

Miller DW, KL Audus, RT Borchardt. (1992). Cultured bovine brain microvessel endothelial cells A model of the blood brain barrier. J Tiss Cult Meth 14 217-224. 

Seetharaman S, Barrand MA, Maskell L, Scheper RJ. Multidmg resistance-related transport proteins in isolated human brain microvessels and in cells cultured from these isolates. J Neurochem 1998 70(3) 1151—1159. 

Regina A, Roman A, Piciotti M, El Hafny B, Center MS, Bergmann R et al. Mrpl multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J Neurochem 1998 71(2)705-715. 

Huai-Yun H, Secrest DT, Mark KS, Carney D, Elmquist WF, Miller W. Expression of multi-drug resistance-associated protein (MRP) in brain microvessel endothelial cells. Biochem Biophys Res Commun 1998 243 816-820. 

Fricker G, Miller D, Bauer B, Nob-mann S, Gutmann H, Torok M et al. Transport of xenobiotics across isolated brain microvessels studied by confocal microscopy. Presented at the 3rd FEBS Advanced Fecture Course - ABC2001 Gosau, Austria. 

The cerebrovasculature is also an abundant source of eicosanoids. Platelets, leukocytes and vascular endothelium are all capable of synthesizing eicosanoids (see above). Brain microvessels isolated from ischemic rat brain demonstrate enhanced synthesis of eicosanoids, and leukocytes and platelets may account for much of the LTD4 produced during ischemia-reperfusion in the gerbil. 

Dorheim, M. A., Tracey, W. R., Pollock, J. S., Grammas, P., Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer s disease, Biochem. Biophys. Res. Commun. 205 (1994), p. 659-665... 

PBEC Porcine brain microvessel endothelial cells... 

The blood-brain barrier forms the interface between the bloodstream and the brain parenchyma and thus controls the passage of endogenous substances and xenobiotics into and out of the central nervous system. Brain microvessels exhibit a variety of unique structural features, such as an extremely tight endothelium without fenestration, a very low rate of pinocytosis, tight junctions between endothelial cells excluding paracellular permeability, and a series of polarized transport proteins. The following chapter describes the structural and functional characteristics of the blood-brain barrier with emphasis on transport proteins, as well as in vitro techniques, which allow studying this complex barrier in the brain. 

Preparation of Porcine Brain Microvessel Endothelial Cells... 

A cell line is a continuously growing cell population, which is derived from tumor cells or from primary cells, which have been immortalized using appropriate vectors. There are several lines of blood-brain barrier endothelial cells available, for example, MBECs (mouse brain endothelial cells), RBE4 cells (rat brain endothelial cells, clone 4), PBMECs (porcine brain microvessel... 

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]. 

Ghersi-Egea JF Minn A, Siest G (1988) A new aspect of the protective functions of the blood-brain barrier Activities of four drug-metabolizing enzymes in isolated brain microvessels. Life Sci 42 2515-2523... 

Zhang, Y, Han, H, Elmquist, WF, MMiiler, DW (2000) Expression of various multidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells. Brain Res 876 148-153. 

Franke H, Gallah HJ, Beuckmann CT (2000) Primary cultures of brain microvessel endothelial cells A valid and flexible method to study drug transport through the blood-brain barrier in vitro. Brain Res Prot 5 248-256... 

Spatz M, Bembry J, Dodson RF, Hervonen H, Murray MR (1980) Endotheial cells culture derived from isolated brain microvessels. Brain Res 191 577-582... 

Shi F, Audus KL (1994) Biochemical characteristics of primary and passaged cultures of primate brain microvessel endothelial cells. Neurochem Res 19 427-433... 

Biegel D, Spencer DD, Pachter JS (1994) Isolation and culture of human brain microvessel endothehal cells for the study of blood-brain barrier properties in vitro. Brain Res 692 183-189... 

Numerous modifications of in vitro culture systems have been developed for the estimation of BBB transfer [52]. Culture systems in use are either primary cultures of brain microvessel endothelial cells (BMEC) or immortalized endothelial cell hues. BMEC may be grown in co-culture with astrocytes or in astrocyte-conditioned medium. Astrocyte-derived factors increase the tightness of the barrier as measured by transendothelial electrical resistance (TEER) and by the permeability of hydrophUic markers such as sucrose. They also up-regulate the expression of BBB-enriched enzymes such as y-glutamyl transpeptidase (y-GTP) and alkaline phosphatase. A setup of the in vitro technique in a transwell system for transport studies is depicted in Figure 2.5. 

Miller, D. W, E. V. Batrakova, T. O. V foltner, V. Y. Alakhov, and A. V. Kabanov. 1997. Interactions of Pluronic block copolymers with brain microvessel endothelial cells evidence of two potential pathways for drug. Bioconj. Chem8 649-657. 

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