Dissecting gene expression at the blood-brain barrier

Frontiers in Neuroscience

Volumn 8, Issue OCT, 2014, Pages

  Huntley, Melanie A ^a   Bien Ly, Nga ^a   Daneman, Richard ^b   Watts, Ryan J ^a  

^a GENENTECH INC   (United States)

^b San Diego   (United States)

Author keywords

Blood brain barrier; Brain endothelial cells; Expression profiling; Genomics; Transcriptome

Indexed keywords

MICRORNA;

ARTICLE; BLOOD BRAIN BARRIER; BRAIN CELL; CELL TYPE; CENTRAL NERVOUS SYSTEM; DRUG DELIVERY SYSTEM; ENDOTHELIUM CELL; EVOLUTION; GENE; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENOMICS; HUMAN; IN SITU HYBRIDIZATION; IN VITRO STUDY; INVERTEBRATE; ISOLATION AND PURIFICATION; NONHUMAN; PRIMATE; PROTEOMICS; RNA SEQUENCE; TRANSCRIPTOMICS;

EID: 84910047887     PISSN: 16624548     EISSN: 1662453X     Source Type: Journal    
DOI: 10.3389/fnins.2014.00355     Document Type: Article

References (120)

1. Abbott, N. J. (2005), Dynamics of CNS barriers: evolution, differentiation, and modulation, Cell Mol Neurobiol., 25, 5-23
2. Adams, R. H. and Alitalo, K. (2007), Molecular regulation of angiogenesis and lymphangiogenesis, Nat Rev Mol Cell Biol., 8, 464-478
3. Agarwal, S., Uchida, Y., Mittapalli, R. K., Sane, R., Terasaki, T., and Elmquist, W. F. (2012), Quantitative proteomics of transporter expression in brain capillary endothelial cells isolated from Pglycoprotein (P-gp), breast cancer resistance protein (Bcrp), and P-gp/Bcrp knockout mice, Drug Metab Dispos., 40, 1164-1169
4. Armulik, A., Genove, G., and Betsholtz, C. (2011), Pericytes: developmental, physiological, and pathological perspectives, problems, and promises, Dev Cell., 21, 193-215
5. Armulik, A., Genove, G., Mae, M., Nisancioglu, M. H., Wallgard, E., Niaudet, C., et al. (2010), Pericytes regulate the blood-brain barrier, Nature., 468, 557-561
6. Badhwar, A., Stanimirovic, D. B., Hamel, E., and Haqqani, A. S. (2014), The proteome of mouse cerebral arteries, J Cereb Blood Flow Metab., 34, 1033-1046
7. Ball, H. J., McParland, B., Driussi, C., and Hunt, N. H. (2002), Isolating vessels from the mouse brain for gene expression analysis using laser capture microdissection, Brain Res Brain Res Protoc., 9, 206-213
8. Banerjee, S., Sousa, A. D., and Bhat, M. A. (2006), Organization and function of septate junctions: an evolutionary perspective, Cell Biochem Biophys., 46, 65-77
9. Barbier, M., Faille, D., Loriod, B., Textoris, J., Camus, C., Puthier, D., et al. (2011), Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria, PLoS One., 6, e19651
10. Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., et al. (2014), Mfsd2a is critical for the formation and function of the blood-brain barrier, Nature., 509, 507-511
11. Betz, A. L., Csejtey, J., and Goldstein, G. W. (1979), Hexose transport and phosphorylation by capillaries isolated from rat brain, Am J Physiol., 236, c96-102
12. Blalock, E. M., Buechel, H. M., Popovic, J., Geddes, J. W., and Landfield, P. W. (2011), Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer's disease, J Chem Neuroanat., 42, 118-126
13. Blalock, E. M., Geddes, J. W., Chen, K. C., Porter, N. M., Markesbery, W. R., and Landfield, P. W. (2004), Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses, Proc Natl Acad Sci U S A., 101, 2173-2178
14. Boado, R. J. and Pardridge, M. M. (1991), A one-step procedure for isolation of poly(A)+ mRNA from isolated brain capillaries and endothelial cells in culture, J Neurochem., 57, 2136-2139
15. Bowman, P. D., Betz, A. L., Ar, D., Wolinsky, J. S., Penney, J. B., Shivers, R. R., et al. (1981), Primary culture of capillary endothelium from rat brain, In Vitro., 17, 353-362
16. Bowyer, J. F., Patterson, T. A., Saini, U. T., Hanig, J. P., Thomas, M., Camacho, L., et al. (2013), Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity, BMC Genomics., 14, 147-2164
17. Calabria, A. R. and Shusta, E. V. (2008), A genomic comparison of in vivo and in vitro brain microvascular endothelial cells, J Cereb Blood Flow Metab., 28, 135-148
18. Cayrol, R., Wosik, K., Berard, J. L., Dodelet-Devillers, A., Ifergan, I., Kebir, H., et al. (2008), Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system, Nat Immunol., 9, 137-145
19. Chun, H. B., Scott, M., Niessen, S., Hoover, H., Baird, A., Yates J,. r. d., et al. (2011), The proteome of mouse brain microvessel membranes and basal lamina, J Cereb Blood Flow Metab., 31, 2267-2281
20. Cunnea, P., McMahon, J., O'Connell, E., Mashayekhi, K., Fitzgerald, U., and McQuaid, S. (2010), Gene expression analysis of the microvascular compartment in multiple sclerosis using laser microdissected blood vessels, Acta Neuropathol., 119, 601-615
21. Daneman, R., Agalliu, D., Zhou, L., Kuhnert, F., Kuo, C. J., and Barres, B. A. (2009), Wnt/betacatenin signaling is required for CNS, but not non-CNS, angiogenesis, Proc Natl Acad Sci U S A., 106, 641-646
22. Daneman, R., Zhou, L., Agalliu, D., Cahoy, J. D., Kaushal, A., and Barres, B. A. (2010a), The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells, PLoS One., 5, e13741
23. Daneman, R., Zhou, L., Kebede, A. A., and Barres, B. A. (2010b), Pericytes are required for bloodbrain barrier integrity during embryogenesis, Nature., 468, 562-566
24. Dauchy, S., Dutheil, F., Weaver, R. J., Chassoux, F., Daumas-Duport, C., Couraud, P. O., et al. (2008), ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier, J Neurochem., 107, 1518-1528
25. Dickey, C. A., Loring, J. F., Montgomery, J., Gordon, M. N., Eastman, P. S., and Morgan, D. (2003), Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice, J Neurosci., 23, 5219-5226
26. Dieterich, L. C., Mellberg, S., Langenkamp, E., Zhang, L., Zieba, A., Salomaki, H., et al. (2012), Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGFbeta2 in vascular abnormalization, J Pathol., 228, 378-390
27. Dorr, A., Sled, J. G., and Kabani, N. (2007), Three-dimensional cerebral vasculature of the CBA mouse brain: a magnetic resonance imaging and micro computed tomography study, Neuroimage., 35, 1409-1423
28. Dunckley, T., Beach, T. G., Ramsey, K. E., Grover, A., Mastroeni, D., Walker, D. G., et al. (2006), Gene expression correlates of neurofibrillary tangles in Alzheimer's disease, Neurobiol Aging., 27, 1359-1371
29. Eadon, M. T., Jacob, A., Cunningham, P. N., Quigg, R. J., Garcia, J. G., and Alexander, J. J. (2014), Transcriptional profiling reveals that C5a alters miRNA in brain endothelial cells, Immunology.
30. Enerson, B. E. and Drewes, L. R. (2006), The rat blood-brain barrier transcriptome, J Cereb Blood Flow Metab., 26, 959-973
31. Engelhardt, B. and Liebner, S. (2014), Novel insights into the development and maintenance of the blood-brain barrier, Cell Tissue Res., 355, 687-699
32. Falcon, S. and Gentleman, R. (2007), Using GOstats to test gene lists for GO term association, Bioinformatics., 23, 257-258
33. Franzen, B., Duvefelt, K., Jonsson, C., Engelhardt, B., Ottervald, J., Wickman, M., et al. (2003), Gene and protein expression profiling of human cerebral endothelial cells activated with tumor necrosis factor-alpha, Brain Res Mol Brain Res., 115, 130-146
34. Gatta, V., D'Aurora, M., Granzotto, A., Stuppia, L., and Sensi, S. L. (2014), Early and sustained altered expression of aging-related genes in young 3xTg-AD mice, Cell Death Dis., 5
35. Geldenhuys, W. J., Allen, D. D., and Bloomquist, J. R. (2012), Novel models for assessing blood-brain barrier drug permeation, Expert Opin Drug Metab Toxicol., 8, 647-653
36. Gentleman, R. C., Carey, V. J., Bates, D. M., Bolstad, B., Dettling, M., Dudoit, S., et al. (2004), Bioconductor: open software development for computational biology and bioinformatics, Genome Biol., 5
37. Giger, T., Khaitovich, P., Somel, M., Lorenc, A., Lizano, E., Harris, L. W., et al. (2010), Evolution of neuronal and endothelial transcriptomes in primates, Genome Biol Evol., 2, 284-292
38. Goetz, I. E., Warren, J., Estrada, C., Roberts, E., and Krause, D. N. (1985), Long-term serial cultivation of arterial and capillary endothelium from adult bovine brain, In Vitro Cell Dev Biol., 21, 172-180
39. Haqqani, A. S., Kelly, J., Baumann, E., Haseloff, R. F., Blasig, I. E., and Stanimirovic, D. B. (2007), Protein markers of ischemic insult in brain endothelial cells identified using 2D gel electrophoresis and ICAT-based quantitative proteomics, J Proteome Res., 6, 226-239
40. Haqqani, A. S., Nesic, M., Preston, E., Baumann, E., Kelly, J., and Stanimirovic, D. (2005), Characterization of vascular protein expression patterns in cerebral ischemia/reperfusion using laser capture microdissection and ICAT-nanoLC-MS/MS, FASEB J., 19, 1809-1821
41. Harris, L. W., Wayland, M., Lan, M., Ryan, M., Giger, T., Lockstone, H., et al. (2008), The cerebral microvasculature in schizophrenia: a laser capture microdissection study, PLoS One., 3, e3964
42. Hawkins, B. T. and Egleton, R. D. (2008), Pathophysiology of the blood-brain barrier: animal models and methods, Curr Top Dev Biol., 80, 277-309
43. He, Z., Cui, L., Patterson, T. A., and Paule, M. G. (2011), Defining the phosphodiesterase superfamily members in rat brain microvessels, ACS Chem Neurosci., 2, 600-607
44. Himburg, H. A., Muramoto, G. G., Daher, P., Meadows, S. K., Russell, J. L., Doan, P., et al. (2010), Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells, Nat Med., 16, 475-482
45. Hudson, L. C., Bragg, D. C., Tompkins, M. B., and Meeker, R. B. (2005), Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells, Brain Res., 1058, 148-160
46. Ifergan, I., Kebir, H., Terouz, S., Alvarez, J. I., Lecuyer, M. A., Gendron, S., et al. (2011), Role of Ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions, Ann Neurol., 70, 751-763
47. Irizarry, R. A., Hobbs, B., Collin, F., Beazer-Barclay, Y. D., Antonellis, K. J., Scherf, U., et al. (2003), Exploration, normalization, and summaries of high density oligonucleotide array probe level data, Biostatistics., 4, 249-264
48. Ito, K., Uchida, Y., Ohtsuki, S., Aizawa, S., Kawakami, H., Katsukura, Y., et al. (2011), Quantitative membrane protein expression at the blood-brain barrier of adult and younger cynomolgus monkeys, J Pharm Sci., 100, 3939-3950
49. Kamiie, J., Ohtsuki, S., Iwase, R., Ohmine, K., Katsukura, Y., Yanai, K., et al. (2008), Quantitative atlas of membrane transporter proteins: development and application of a highly sensitive simultaneous LC/MS/MS method combined with novel in-silico peptide selection criteria, Pharm Res., 25, 1469-1483
50. Kauffmann, A., Gentleman, R., and Huber, W. (2009), arrayQualityMetrics-a bioconductor package for quality assessment of microarray data, Bioinformatics., 25, 415-416
51. Krause, G., Winkler, L., Mueller, S. L., Haseloff, R. F., Piontek, J., and Blasig, I. E. (2008), Structure and function of claudins, Biochim Biophys Acta., 1778, 631-645
52. Lazarov, O., Robinson, J., Tang, Y. P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M., et al. (2005), Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice, Cell., 120, 701-713
53. Li, J. Y., Boado, R. J., and Pardridge, W. M. (2001), Blood-brain barrier genomics, J Cereb Blood Flow Metab., 21, 61-68
54. Li, K., Dong, D., Yao, L., Dai, D., Gu, X., and Guo, L. (2008), Identification of STC1 as an betaamyloid activated gene in human brain microvascular endothelial cells using cDNA microarray, Biochem Biophys Res Commun., 376, 399-403
55. Liddelow, S. A., Dziegielewska, K. M., Ek, C. J., Habgood, M. D., Bauer, H., Bauer, H. C., et al. (2013), Mechanisms that determine the internal environment of the developing brain: a transcriptomic, functional and ultrastructural approach, PLoS One., 8, e65629
56. Liddelow, S. A., Temple, S., Mollgard, K., Gehwolf, R., Wagner, A., Bauer, H., et al. (2012), Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach, PLoS One., 7, e33554
57. Liebner, S., Corada, M., Bangsow, T., Babbage, J., Taddei, A., Czupalla, C. J., et al. (2008), Wnt/betacatenin signaling controls development of the blood-brain barrier, J Cell Biol., 183, 409-417
58. Liebner, S., Fischmann, A., Rascher, G., Duffner, F., Grote, E. H., Kalbacher, H., et al. (2000), Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme, Acta Neuropathol., 100, 323-331
59. Lindahl, P., Johansson, B. R., Leveen, P., and Betsholtz, C. (1997), Pericyte loss and microaneurysm formation in PDGF-B-deficient mice, Science., 277, 242-245
60. Lister, R., O'Malley, R. C., Tonti-Filippini, J., Gregory, B. D., Berry, C. C., Millar, A. H., et al. (2008), Highly integrated single-base resolution maps of the epigenome in Arabidopsis, Cell., 133, 523-536
61. Lopez-Ramirez, M. A., Male, D. K., Wang, C., Sharrack, B., Wu, D., and Romero, I. A. (2013), Cytokine-induced changes in the gene expression profile of a human cerebral microvascular endothelial cell-line, hCMEC/D3, Fluids Barriers CNS., 10, 27-8118
62. Lu, L., Yang, P. Y., Rui, Y. C. h., Kang, H., Zhang, J., Zhang, J. P., et al. (2007), Comparative proteome analysis of rat brain and coronary microvascular endothelial cells, Physiol Res., 56, 159-168
63. Lu, Q., Murugesan, N., Macdonald, J. A., Wu, S. L., Pachter, J. S., and Hancock, W. S. (2008), Analysis of mouse brain microvascular endothelium using immuno-laser capture microdissection coupled to a hybrid linear ion trap with Fourier transform-mass spectrometry proteomics platform, Electrophoresis., 29, 2689-2695
64. Lyck, R., Ruderisch, N., Moll, A. G., Steiner, O., Cohen, C. D., Engelhardt, B., et al. (2009), Cultureinduced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo, J Cereb Blood Flow Metab., 29, 1491-1502
65. Macdonald, J. A., Murugesan, N., and Pachter, J. S. (2008), Validation of immuno-laser capture microdissection coupled with quantitative RT-PCR to probe blood-brain barrier gene expression in situ, J Neurosci Methods., 174, 219-226
66. Macdonald, J. A., Murugesan, N., and Pachter, J. S. (2010), Endothelial cell heterogeneity of bloodbrain barrier gene expression along the cerebral microvasculature, J Neurosci Res., 88, 1457-1474
67. Marques, F., Sousa, J. C., Sousa, N., and Palha, J. A. (2013), Blood-brain-barriers in aging and in Alzheimer's disease, Mol Neurodegener., 8, 38-1326
68. Marroni, M., Kight, K. M., Hossain, M., Cucullo, L., Desai, S. Y., and Janigro, D. (2003), Dynamic in vitro model of the blood-brain barrier. Gene profiling using cDNA microarray analysis, Methods Mol Med., 89, 419-434
69. Masuda, S., Oda, Y., Sasaki, H., Ikenouchi, J., Higashi, T., Akashi, M., et al. (2011), LSR defines cell corners for tricellular tight junction formation in epithelial cells, J Cell Sci., 124, 548-555
70. Mayer, F., Mayer, N., Chinn, L., Pinsonneault, R. L., Kroetz, D., and Bainton, R. J. (2009), Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila, J Neurosci., 29, 3538-3550
71. McCandless, E. E., Budde, M., Lees, J. R., Dorsey, D., Lyng, E., and Klein, R. S. (2009), IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis, J Immunol., 183, 613-620
72. McCandless, E. E., Wang, Q., Woerner, B. M., Harper, J. M., and Klein, R. S. (2006), CXCL12 limits inflammation by localizing mononuclear infiltrates to the perivascular space during experimental autoimmune encephalomyelitis, J Immunol., 177, 8053-8064
73. Mojsilovic-Petrovic, J., Nesic, M., Pen, A., Zhang, W., and Stanimirovic, D. (2004), Development of rapid staining protocols for laser-capture microdissection of brain vessels from human and rat coupled to gene expression analyses, J Neurosci Methods., 133, 39-48
74. Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., and Wold, B. (2008), Mapping and quantifying mammalian transcriptomes by RNA-Seq, Nat Methods., 5, 621-628
75. Murugesan, N., Macdonald, J. A., Lu, Q., Wu, S. L., Hancock, W. S., and Pachter, J. S. (2011), Analysis of mouse brain microvascular endothelium using laser capture microdissection coupled with proteomics, Methods Mol Biol., 686, 297-311
76. Nagalakshmi, U., Wang, Z., Waern, K., Shou, C., Raha, D., Gerstein, M., et al. (2008), The transcriptional landscape of the yeast genome defined by RNA sequencing, Science., 320, 1344-1349
77. Navone, S. E., Marfia, G., Invernici, G., Cristini, S., Nava, S., Balbi, S., et al. (2013), Isolation and expansion of human and mouse brain microvascular endothelial cells, Nat Protoc., 8, 1680-1693
78. Nguyen, L. N., Ma, D., Shui, G., Wong, P., Cazenave-Gassiot, A., Zhang, X., et al. (2014), Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid, Nature., 509, 503-506
79. Nielsen, P. A., Andersson, O., Hansen, S. H., Simonsen, K. B., and Andersson, G. (2011), Models for predicting blood-brain barrier permeation, Drug Discov Today., 16, 472-475
80. Nitta, T., Hata, M., Gotoh, S., Seo, Y., Sasaki, H., Hashimoto, N., et al. (2003), Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice, J Cell Biol., 161, 653-660
81. Obermeier, B., Daneman, R., and Ransohoff, R. M. (2013), Development, maintenance and disruption of the blood-brain barrier, Nat Med., 19, 1584-1596
82. Ohtsuki, S., Ikeda, C., Uchida, Y., Sakamoto, Y., Miller, F., Glacial, F., et al. (2013), Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood-brain barrier model, Mol Pharm., 10, 289-296
83. Ouyang, S., Hsuchou, H., Kastin, A. J., Wang, Y., Yu, C., and Pan, W. (2014), Diet-induced obesity suppresses expression of many proteins at the blood-brain barrier, J Cereb Blood Flow Metab., 34, 43-51
84. Pen, A., Moreno, M. J., Martin, J., and Stanimirovic, D. B. (2007), Molecular markers of extracellular matrix remodeling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels, Glia., 55, 559-572
85. Pfeiffer, F., Schafer, J., Lyck, R., Makrides, V., Brunner, S., Schaeren-Wiemers, N., et al. (2011), Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis, Acta Neuropathol., 122, 601-614
86. Pottiez, G., Deracinois, B., Duban-Deweer, S., Cecchelli, R., Fenart, L., Karamanos, Y., et al. (2010), A large-scale electrophoresis- and chromatography-based determination of gene expression profiles in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties, Proteome Sci., 8, 57-5956
87. Pottiez, G., Flahaut, C., Cecchelli, R., and Karamanos, Y. (2009), Understanding the blood-brain barrier using gene and protein expression profiling technologies, Brain Res Rev., 62, 83-98
88. Qiu, S., Luo, S., Evgrafov, O., Li, R., Schroth, G. P., Levitt, P., et al. (2012), Single-neuron RNA-Seq: technical feasibility and reproducibility, Front Genet., 3, 124
89. Reddy, P. H., McWeeney, S., Park, B. S., Manczak, M., Gutala, R. V., Partovi, D., et al. (2004), Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease, Hum Mol Genet., 13, 1225-1240
90. Reese, T. S. and Karnovsky, M. J. (1967), Fine structural localization of a blood-brain barrier to exogenous peroxidase, J Cell Biol., 34, 207-217
91. Reijerkerk, A., Lopez-Ramirez, M. A., van Het Hof, B., Drexhage, J. A., Kamphuis, W. W., Kooij, G., et al. (2013), MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis, J Neurosci., 33, 6857-6863
92. Risau, W., Hallmann, R., and Albrecht, U. (1986), Differentiation-dependent expression of proteins in brain endothelium during development of the blood-brain barrier, Dev Biol., 117, 537-545
93. Saunders, N. R., Daneman, R., Dziegielewska, K. M., and Liddelow, S. A. (2013), Transporters of the blood-brain and blood-CSF interfaces in development and in the adult, Mol Aspects Med., 34, 742-752
94. Schwabe, T., Bainton, R. J., Fetter, R. D., Heberlein, U., and Gaul, U. (2005), GPCR signaling is required for blood-brain barrier formation in drosophila, Cell., 123, 133-144
95. Searcy, J. L., Le Bihan, T., Salvadores, N., McCulloch, J., and Horsburgh, K. (2014), Impact of age on the cerebrovascular proteomes of wild-type and Tg-SwDI mice, PLoS One., 9, e89970
96. Shawahna, R., Uchida, Y., Decleves, X., Ohtsuki, S., Yousif, S., Dauchy, S., et al. (2011), Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels, Mol Pharm., 8, 1332-1341
97. Shusta, E. V. (2005), Blood-brain barrier genomics, proteomics, and new transporter discovery, NeuroRx., 2, 151-161
98. Shusta, E. V., Boado, R. J., Mathern, G. W., and Pardridge, W. M. (2002), Vascular genomics of the human brain, J Cereb Blood Flow Metab., 22, 245-252
99. Siegenthaler, J. A., Sohet, F., and Daneman, R. (2013), 'Sealing off the CNS': cellular and molecular regulation of blood-brain barriergenesis, Curr Opin Neurobiol., 23, 1057-1064
100. Smyth, G. K. (2004), Linear models and empirical bayes methods for assessing differential expression in microarray experiments, Stat Appl Genet Mol Biol., 3
101. Stenman, J. M., Rajagopal, J., Carroll, T. J., Ishibashi, M., McMahon, J., and McMahon, A. P. (2008), Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature, Science., 322, 1247-1250
102. Stork, T., Engelen, D., Krudewig, A., Silies, M., Bainton, R. J., and Klambt, C. (2008), Organization and function of the blood-brain barrier in Drosophila, J Neurosci., 28, 587-597
103. Tam, S. J., Richmond, D. L., Kaminker, J. S., Modrusan, Z., Martin-McNulty, B., Cao, T. C., et al. (2012), Death receptors DR6 and TROY regulate brain vascular development, Dev Cell., 22, 403- 417
104. Tam, S. J. and Watts, R. J. (2010), Connecting vascular and nervous system development: angiogenesis and the blood-brain barrier, Annu Rev Neurosci., 33, 379-408
105. Triguero, D., Buciak, J., and Pardridge, W. M. (1990), Capillary depletion method for quantification of blood-brain barrier transport of circulating peptides and plasma proteins, J Neurochem., 54, 1882- 1888
106. Uchida, Y., Ohtsuki, S., Katsukura, Y., Ikeda, C., Suzuki, T., Kamiie, J., et al. (2011), Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors, J Neurochem., 117, 333-345
107. Urich, E., Lazic, S. E., Molnos, J., Wells, I., and Freskgard, P. O. (2012), Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models, PLoS One., 7, e38149
108. Vinters, H. V., Reave, S., Costello, P., Girvin, J. P., and Moore, S. A. (1987), Isolation and culture of cells derived from human cerebral microvessels, Cell Tissue Res., 249, 657-667
109. Wang, S., Qaisar, U., Yin, X., and Grammas, P. (2012a), Gene expression profiling in Alzheimer's disease brain microvessels, J Alzheimers Dis., 31, 193-205
110. Wang, Y., Rattner, A., Zhou, Y., Williams, J., Smallwood, P. M., and Nathans, J. (2012b), Norrin/ Frizzled4 signaling in retinal vascular development and blood brain barrier plasticity, Cell., 151, 1332-1344
111. Webster, J. A., Gibbs, J. R., Clarke, J., Ray, M., Zhang, W., Holmans, P., et al. (2009), Genetic control of human brain transcript expression in Alzheimer disease, Am J Hum Genet., 84, 445-458
112. Wilhelm, B. T., Marguerat, S., Watt, S., Schubert, F., Wood, V., Goodhead, I., et al. (2008), Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution, Nature., 453, 1239-1243
113. Wolburg, H., Wolburg-Buchholz, K., Kraus, J., Rascher-Eggstein, G., Liebner, S., Hamm, S., et al. (2003), Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme, Acta Neuropathol., 105, 586-592
114. Wosik, K., Cayrol, R., Dodelet-Devillers, A., Berthelet, F., Bernard, M., Moumdjian, R., et al. (2007), Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis, J Neurosci., 27, 9032-9042
115. Wu, V. M. and Beitel, G. J. (2004), A junctional problem of apical proportions: epithelial tube-size control by septate junctions in the Drosophila tracheal system, Curr Opin Cell Biol., 16, 493-499
116. Yousif, S., Marie-Claire, C., Roux, F., Scherrmann, J. M., and Decleves, X. (2007), Expression of drug transporters at the blood-brain barrier using an optimized isolated rat brain microvessel strategy, Brain Res., 1134, 1-11
117. Yu, Y. J. and Watts, R. J. (2013), Developing therapeutic antibodies for neurodegenerative disease, Neurotherapeutics., 10, 459-472
118. Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., et al. (2014), An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex, J Neurosci., 34, 11929-11947
119. Zhou, L., Sohet, F., and Daneman, R. (2014a), Purification and culture of central nervous system endothelial cells, Cold Spring Harb Protoc., 2014, 44-46
120. Zhou, Y., Wang, Y., Tischfield, M., Williams, J., Smallwood, P. M., Rattner, A., et al. (2014b), Canonical WNT signaling components in vascular development and barrier formation, J Clin Invest., 124, 3825-3846