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Morphology and Molecular Properties of Cellular Components of Normal Cerebral Vessels

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Book cover The Blood-Brain Barrier

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 89))

Abstract

The blood-brain barrier (BBB) includes anatomical, physicochemical, and biochemical mechanisms that control the exchange of materials between blood and brain and cerebrospinal fluid (CSF). Thus two distinct systems, the BBB and the blood-CSF barrier systems, control cerebral homeostasis. However, both systems are unique, the BBB having a 5000-fold greater surface area than the blood-CSF barrier (1,2). The concentrations of substances in brain interstitium, which is determined by transport through the BBB, can differ markedly from concentrations in CSF, the composition of which is determined by secretory processes in the choroid plexus epithelia (3). This review will focus on cellular components of cerebral vessels with emphasis on endothelium, basement membrane, and pericytes as well as the perivascular macrophage (Figs. 1 and 2 A), which in light of new information is distinct from pericytes. This review deals less with pathogenesis and more with some of the molecules that have been discovered in these cell types in the past decade. Although astrocytes invest 99% of the brain surface of the capillary basement membrane and are important in induction and maintenance of the BBB, this topic will not be discussed and readers are referred to reviews in the literature (4–11).

Segment of normal cerebral cortical capillary wall consists of endothelium (e) and a pericyte (p) separated by basement membrane. This rat was injected with ionic lanthanum, which has penetrated the interendothelial space upto the tight junction (arrowhead). ×70,000.

(see facing page) (A) A cryostat section shows perivascular macrophages using anti-ED2 antibody. The inset shows these cells at higher magnification. Note that these cells are associated with vessels, which have the caliber of veins and not capillaries. (C,D) Merged confocal images of normal rat brain dual labeled for Ang-1 and Ang-2 proteins. Normal vessels show endothelial localization of Ang-1 (green) only in rat brain (B) and choroid plexuses (C) and there is no detectable localization of Ang-2. Note the granular immunostaining in choroid plexus epithelial cells indicating colocalization of Ang-1 and Ang-2 (yellow). (D) Cultured cells derived from cerebral microvessels show adherance of antibody-coated ox red blood cells forming rosettes indicating presence of Fc receptors. Note that many of these cells contain Factor VIII indicating that they are endothelial cells (arrowheads). (E) Electron micrograph demonstrating that the cells to which antibody-coated ox red cells have adhered also show cytoplasmic Factor VIII immunostaining indicating its endothelial nature. Scale bar A−C=50 μm; Inset=25 μm; D×100; E×8000.

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References

  1. Crone, C. (1971) The blood-brain barrier—facts and questions. In Ion Homeostasis of the Brain. (Siesjo, B. K., and Sorensen, S. C., eds.) Munksgaard, Copenhagen, pp. 52–62.

    Google Scholar 

  2. Pardridge, W. M., Frank, H. J. L., Cornford, E. M., Braun, L. D., Crane, P. D., and Oldendorf, W. H. (1981) Neuropeptides and the blood-brain barrier. In Neurosecretion and Brain Peptides. (Martin, J. B., Reichlin, S., and Bick, K. L., eds.) Raven, New York, pp. 321–328.

    Google Scholar 

  3. Hutson, P. H., Sarna, G. S., Katananeni, B. D., and Curzon, G. (1985) Monitoring effects of tryptophan load on endometabolism in freely moving rats by simultaneous cerebrospinal fluid sampling and brain dialysis. J. Neurochem. 44, 1266–1273.

    Article  PubMed  CAS  Google Scholar 

  4. DeBault, L., and Cancilla, P. A. (1980) γ-glutamyl transpeptidase in isolated brain endothelial cells: induction by glial cells in vitro. Science 207, 635–645.

    Article  Google Scholar 

  5. Janzer, R. C, and Raff, M. C. (1987) Astrocytes induce blood-brain properties in endothelial cells. Nature 325, 253–257.

    Article  PubMed  CAS  Google Scholar 

  6. Kacem, K., LaCombe, P., Seylaz, J., and Bonvento, G. (1998) Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23, 1–10.

    Article  PubMed  CAS  Google Scholar 

  7. Laterra, J., Guerin, C, and Goldstein, G. W. (1990) Astrocytes induce neural microvascular endothelial cells to form capillary-like structures in vitro. J. Cell Physiol. 144, 204–215.

    Article  PubMed  CAS  Google Scholar 

  8. Pardridge, W. M. (1995) The Blood-Brain Barrier. Cellular and Molecular Biology. Raven, New York, pp. 137–164.

    Google Scholar 

  9. Pardridge, W. M. (1998) Introduction to the Blood-Brain Barrier. Methodology, Biology and Pathology. Cambridge University Press, Cambridge, UK.

    Book  Google Scholar 

  10. Peters, A., Palay, S. L., and DeF Webster, H. (1976) The Fine Structure of the Nervous System: The Neurons and Supporting Cells. W.B. Saunders Co., Philadelphia.

    Google Scholar 

  11. Raub, T. J., Kuentzel, S. L., and Sawada, G A. (1992) Permeability of bovine brain microvessel endothelial cells in vitro: barrier tightening by a factor released from astroglioma cells. Exp. Cell Res. 199, 330–340.

    Article  PubMed  CAS  Google Scholar 

  12. Crone, C. (1963) The permeability of capillaries in various organs as determined by use of the ‘indicator diffusion’ method. Acta Physiol. Scand. 58, 292–305.

    Article  PubMed  CAS  Google Scholar 

  13. Kalaria, R. N, Gravina, S. A., Schmidley, J. W., Perry, G., and Harik, S. I. (1988) The glucose transporter of the human brain and blood-brain barrier. Ann. Neurol. 24, 757–764.

    Article  PubMed  CAS  Google Scholar 

  14. Albert, Z., Orlowski, M., Rzucidlo, Z., and Orlowska, J. (1966) Studies on γ-glutamyl transpeptidase activity and its histochemical localization in the central nervous system of man and different species. Acta Histochem. 25, 312–320.

    PubMed  CAS  Google Scholar 

  15. Risau, W., Hallmann, R., Albrecht, U, and Henke-Fahle, S. (1986) Brain induces the expression of an early cell surface marker for blood-brain barrier-specific endothelium. EMBO J. 5, 3179–3183.

    PubMed  CAS  Google Scholar 

  16. Schlosshauer, B., and Herzog, K.-H. (1990) Neurothelin: inducible cell surface glycoprotein on blood-brain barrier-specific endothelial cells and distinct neurons. J. Cell Biol. 110, 1261–1274.

    Article  PubMed  CAS  Google Scholar 

  17. Prat, A., Biernacki, K., Pouly, S., Nalbantoglu, J., Couture, R., and Antel, J. P. (2000) Kinin B1 receptor expression and function on human brain endothelial cells. J. Neuropathol. Exp. Neurol. 59, 896–906.

    PubMed  CAS  Google Scholar 

  18. Fossum, S., Mallett, S., and Barclay, A. N. (1991) The MRC OX-47 antigen is a member of the immunoglobulin superfamily with an unusual transmembrane sequence. Eur. J. Immunol. 21, 671–679.

    Article  PubMed  CAS  Google Scholar 

  19. Sternberger, N. H., and Sternberger, L. A. (1987) Blood-brain barrier protein recognized by monoclonal antibody. Proc. Natl. Acad. Sci. USA 84, 8169–8173.

    Article  PubMed  CAS  Google Scholar 

  20. Cassella, J. P., Lawrenson, J. G., Lawrence, L., and Firth, J. A. (1997) Differential distribution of an endothelial barrier antigen between the pial and cortical microvessels of the rat. Brain Res. 744, 335–338.

    Article  PubMed  CAS  Google Scholar 

  21. Jefferies, W. A., Brandon, M. R., Hunt, S. V., Williams, A. F., Gatter, K. C, and Mason, D. Y. (1984) Transferrin receptor on endothelium of brain capillaries. Nature 312, 162–163.

    Article  PubMed  CAS  Google Scholar 

  22. Dermietzel, R., and Krause, D. (1991) Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry. Int. Rev. Cytol. 127, 57–109.

    Article  PubMed  CAS  Google Scholar 

  23. Liebner, S., Kniesel, U., Kalbacher, H., and Hartwig, W. (2000) Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur. J. Cell Biol. 79, 707–717.

    Article  PubMed  CAS  Google Scholar 

  24. Weber, T., Seitz, R. J., Liebert, U. G., Gallasch, E., and Wechsler, W. (1995) Affinity cytochemistry of vascular endothelia in brain tumors by biotinylated Ulex europaeus type I lectin (UEA I). Acta Neuropathol. (Berl.) 67, 128–135.

    Article  Google Scholar 

  25. Nag, S., Eskandarian, M. R., Davis, J., and Stewart, D. J. (2002) Differential expression of vascular endothelial growth factor A and B after brain injury. J. Neuropathol. Exp. Neurol. 61, 778–788.

    PubMed  CAS  Google Scholar 

  26. Nourhaghighi, N., Stewart, D. J., and Nag, S. (2000) Immunohistochemical characterization of Angiopoietin-1, Angiopoietin-2, and Tie-2 in an in vivo model of cerebral trauma and angiogenesis. Brain Pathol. 10, 555.

    Google Scholar 

  27. Nag, S., Picard, P., and Stewart, D. J. (2001) Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury. Lab. Invest. 81, 41–49.

    PubMed  CAS  Google Scholar 

  28. Plate, K. H. (1999) Mechanisms of angiogenesis in the brain. J. Neuropathol. Exp. Neurol. 58, 313–320.

    Article  PubMed  CAS  Google Scholar 

  29. Risau, W. (1997) Mechanisms of angiogenesis. Nature 386, 671–674.

    Article  PubMed  CAS  Google Scholar 

  30. Nag, S. (2002) The blood-brain barrier and cerebral angiogenesis: lessons from the cold-injury model. Trends Mol. Med. 8, 38–44.

    Article  PubMed  CAS  Google Scholar 

  31. Dvorak, H. F, Nagy, J. A., Feng, D., Brown, L. F, and Dvorak, A. M. (1999) Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr. Top. Microbiol. Immunol. 237, 97–132.

    PubMed  CAS  Google Scholar 

  32. Nag, S., Takahashi, J. T, and Kilty, D. (1997) Role of vascular endothelial growth factor in blood-brain barrier breakdown and angiogenesis in brain trauma. J. Neuropathol. Exp. Neurol. 56, 912–921.

    Article  PubMed  CAS  Google Scholar 

  33. Risau, W. (1994) Molecular biology of blood-brain barrier ontogenesis and function. Acta Neurochir. (Suppl.) 60, 109–112.

    CAS  Google Scholar 

  34. Robertson, P. L., Du Bois, M., Bowman, P. D., and Goldstein, G. W. (1985) Angiogenesis in developing rat brain: an in vivo and in vitro study. Dev. Brain Res. 23, 219–223.

    Article  Google Scholar 

  35. Engerman, R. L., Pfaffenbach, D., and Davis, M. D., (1967) Cell turnover of capillaries. Lab. Invest. 17, 738–743.

    PubMed  CAS  Google Scholar 

  36. Stewart, P. A., and Wiley, M. J. (1981) Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev. Biol. 84, 183–192.

    Article  PubMed  CAS  Google Scholar 

  37. Breier, G., Albrecht, U., Sterrer, S., and Risau, W. (1992) Expression of vascular endothelial growth-factor during embryonic angiogenesis and endothelial-cell differentiation. Development 114, 521–532.

    PubMed  CAS  Google Scholar 

  38. Devries, C., Escobedo, J. A., Ueno, H., Houck, K., Ferrara, N., and Williams, L. T (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth-factor. Science 255, 989–991.

    Article  CAS  Google Scholar 

  39. Millauer, B., Wizigmann-Voos, S., Schnürch, H., et al. (1993) High affinity VEGF binding and developmental expression suggests Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72, 835–846.

    Article  PubMed  CAS  Google Scholar 

  40. Risau, W., and Wolburg, H. (1991) The importance of the blood-brain barrier in fetuses and embryos—reply. TINS 14, 14–15.

    Google Scholar 

  41. Croll, S. D., and Wiegand, S. J. (2001) Vascular growth factors in cerebral ischemia. Mol. Neurobiol. 23, 121–135.

    Article  PubMed  CAS  Google Scholar 

  42. Plate, K. H., Beck, H., Danner, S., Allegrini, P. R., and Wiessner, C. (1999) Cell type specific upregulation of vascular endothelial growth factor in a MCA-occlusion model of cerebral infarct. J. Neuropathol. Exp. Neurol. 58, 654–666.

    Article  PubMed  CAS  Google Scholar 

  43. Mandriota, S. J., Pyke, C., Di Sanza, C., Quindoz, P., Pittet, B., and Pepper, M. S. (2000) Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia. Amer. J. Pathol. 156, 2077–2089.

    Article  CAS  Google Scholar 

  44. Maisonpierre, P. C., Suri, C, Jones, P. F., et al. (1997) Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in vivo angiogenesis. Science 277, 55–60.

    Article  PubMed  CAS  Google Scholar 

  45. Folkman, J., and D’Amore, P. A. (1996) Blood vessel formation: What is its molecular basis? Cell 87, 1153–1155.

    Article  PubMed  CAS  Google Scholar 

  46. Nag, S., Nourhaghighi, N., Teichert-Kuliszewska, K., Davis, J., Papneja, T., and Stewart, D. J. (2002) Altered expression of angiopoietins during blood-brain barrier breakdown and angiogenesis. J. Neuropathol. Exp. Neurol. 61, 453.

    Google Scholar 

  47. Stratmann, A., Risau, W., and Plate, K. H. (1998) Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Am. J. Pathol. 153, 1459–1466.

    Article  PubMed  CAS  Google Scholar 

  48. Zagzag, D., Hooper, A., Friedlander, D. R., et al. (1999) In situ expression of angiopoietins in astrocytomas identifies angiopoietin-2 as an early marker of tumor angiogenesis. Exp. Neurol. 159, 391–400.

    Article  PubMed  CAS  Google Scholar 

  49. Beck, H., Acker, T., Wiessner, C., Allergrini, P. R., and Plate, K. (2000) Expression of Angiopoietin-1 and Angiopoietin-2, and Tie-2 receptors after middle cerebral artery occlusion in the rat. Am. J. Pathol. 157, 1473–1483.

    Article  PubMed  CAS  Google Scholar 

  50. Lin, T. N., Wang, C.-K., Cheung, W.-M., and Hsu, C.-Y. (2000) Induction of angiopoietin and Tie Receptor mRNA expression after cerebral ischemia-reperfusion. J. Cereb. Blood Flow Metab. 20, 387–395.

    Article  PubMed  CAS  Google Scholar 

  51. Muir, A. R, and Peters, A. (1962) Quintuple-layered membrane junctions at terminal bars between endothelial cells. J. Cell Biol. 12, 443–447.

    Article  PubMed  CAS  Google Scholar 

  52. Brightman, M. W., and Reese, T. S. (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40, 648–677.

    Article  PubMed  CAS  Google Scholar 

  53. Nag, S., Dinsdale, H. B., and Robertson, D. M. (1977) Cerebral cortical changes in acute experimental hypertension. An ultrastructural study. Lab. Invest. 36, 150–161.

    PubMed  CAS  Google Scholar 

  54. 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.

    Article  PubMed  CAS  Google Scholar 

  55. Feder, N., Reese, T. S., and Brightman, M. (1969) Microperoxidase, a new tracer of low molecular weight. A study of the interstitial compartments of the mouse brain. J. Cell Biol. 43, 35a–36a.

    Google Scholar 

  56. Dermietzel, R. (1975) Junctions in the central nervous system of the cat. V. The junctional complex of the pia-arachnoid membrane. Cell Tissue Res. 164, 309–329.

    PubMed  CAS  Google Scholar 

  57. Nabeshima, S., Reese, T. S., Landis, D. M. D., and Brightman, M. W. (1975) Junctions in the meninges and marginal glia. J. Comp. Neurol. 164, 127–169.

    Article  PubMed  CAS  Google Scholar 

  58. Dermietzel, R., Meller, N., Tetzlaff, W., and Waelsch, M. (1977) In vivo and in vitro formation of the junctional complex in choroid epithelium. A freeze-etching study. Cell Tissue Res. 181, 427–441.

    Article  PubMed  CAS  Google Scholar 

  59. van Deurs, B. (1980) Structural aspects of brain barriers, with special reference to the permeability of the cerebral endothelium and choroidal epithelium. Int. Rev. Cytol. 65, 117–191.

    Article  PubMed  Google Scholar 

  60. Nag, S. (1991) Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier. Acta Neuropathol. (Berl.) 82, 274–279.

    Article  CAS  Google Scholar 

  61. Brightman, M. W., and Palay, S. L. (1963) The fine structure of ependyma in the brain of the rat. J. Cell Biol. 19, 415–439.

    Article  PubMed  CAS  Google Scholar 

  62. Bouchaud, C., and Bosler, O. (1986) The circumventricular organs of the mammalian brain with special reference to monoaminergic innervation. Int. Rev. Cytol. 105, 283–327.

    Article  PubMed  CAS  Google Scholar 

  63. Gross, P. M., Sposito, N. M., Pettersen, S. E., and Fenstermacher, J. D. (1986) Differences in function and structure of the capillary endothelium in gray matter, white matter and a circumventricular organ of rat brain. Blood Vessels 23, 261–270.

    PubMed  CAS  Google Scholar 

  64. Weindl, A. (1973) Neuroendocrine aspects of circumventricular organs. In Frontiers in Neuroendocrinology. (Ganong, W. F., and Martin, L., eds), Oxford University Press, New York, pp. 3–32.

    Google Scholar 

  65. Krisch, B., and Leonhardt, H. (1989) Relations between leptomeningeal compartments and the neurohemal regions of circumventricular organs. Biomed. Res. 10, 155–168.

    Google Scholar 

  66. Nagy, Z., Peters, H., and Hüttner, I. (1984) Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab. Invest. 50, 313–322.

    PubMed  CAS  Google Scholar 

  67. Kniesel, U., and Wolburg, H. (2000) Tight junctions of the blood-brain barrier. Cell Mol. Neurobiol. 20, 57–74.

    Article  PubMed  CAS  Google Scholar 

  68. Brightman, M. W., and Tao-Cheng, J. H. (1993) Tight junctions of brain endothelium and epithelium. In The Blood-Brain Barrier. Cellular and Molecular Biology. (Pardridge, W. M., ed.), Raven, New York, pp. 107–125.

    Google Scholar 

  69. van Deurs, B., and Koehler, J. K. (1979) Tight junctions in the choroid plexus epithelium, a freeze fracture study including complementary replicas. J. Cell Biol. 80, 662–673.

    Article  PubMed  Google Scholar 

  70. Connell, C. J., and Mercer, K. L. (1974) Freeze-fracture appearance of the capillary endothelium in the cerebral cortex of mouse brain. Am. J. Anat. 140, 595–599.

    Article  PubMed  CAS  Google Scholar 

  71. Farrell, C. L., and Shivers, R. R. (1984) Capillary junctions of the rat are not affected by osmotic opening of the blood-brain barrier. Acta Neuropathol. (Berl.) 63, 179–189.

    Article  CAS  Google Scholar 

  72. Shivers, R. R., Edmonds, C. L., and Del Maestro, R. F (1984) Microvascular permeability in induced astrocytomas and peritumor neuropil of rat brain. A high-voltage electron microscope-protein tracer study. Acta Neuropathol. (Berl.) 64, 192–202.

    Article  CAS  Google Scholar 

  73. Krause, D., Mischeck, U., Galla, H. J., and Dermietzel, R. (1991) Correlation of zonula occludens ZO-1 antigen and transendothelial resistance in porcine and rat cultured cerebral endothelial cells. Neurosci. Letts. 128, 301–304.

    Article  CAS  Google Scholar 

  74. Crone, C, and Olesen, S. P. (1982) Electrical resistance of brain microvascular endothelium. Brain Res. 241, 49–55.

    Article  PubMed  CAS  Google Scholar 

  75. Smith, Q. R., and Rapoport, S. I. (1986) Cerebrovascular permeability coefficients to sodium, potassium and chloride. J. Neurochem. 46, 1732–1742.

    Article  PubMed  CAS  Google Scholar 

  76. Tilling, T., Korte, D., Hoheisel, D., and Galla, H. J. (1998) Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J. Neurochem. 71, 1151–1157.

    Article  PubMed  CAS  Google Scholar 

  77. Kondo, T, Kinouchi, H., Kawase, M., and Yoshimoto, T. (1996) Astroglial cells inhibit the increasing permeability of brain endothelial cell monolayer following hypoxia/ reoxygenation. Neurosci. Letts. 208, 101–104.

    Article  CAS  Google Scholar 

  78. Igarashi, Y, Utsumi, H., Chiba, H., et al. (1999) Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem. Biophys. Res. Commun. 261, 108–112.

    Article  PubMed  CAS  Google Scholar 

  79. Perez-Gomez, J., Bindslev, N., Orkand, P. M., and Wright, E. M. (1976) Electrical properties and structure of the frog arachnoid membrane. J. Neurobiol. 7, 259–270.

    Article  PubMed  CAS  Google Scholar 

  80. Frömter, E., and Diamond, J. (1972) Route of passive ion permeation in epithelia. Nature 235, 9–13.

    Article  Google Scholar 

  81. Furuse, M., Fujita, K., Hiiragi, T., Fujimoto, K., and Tsukita, S. (1998) Claudin-1 and-2: Novel integral membrane proteins localizing at tight junctions. J. Cell Biol. 141, 1539–1550.

    Article  PubMed  CAS  Google Scholar 

  82. Furuse, M., Hirase, T., Ito, M., et al. (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 123, 1777–1788.

    Article  PubMed  CAS  Google Scholar 

  83. Martìn-Padura, I., Lostaglio, S., Schneemann, M., et al. (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J. Cell Biol. 142, 117–127.

    Article  PubMed  Google Scholar 

  84. Furuse, M., Sasaki, H., and Tsukita, S. (1999) Manner of interaction of heterogenous claudin species within and between tight junction strands. J. Cell Biol. 147, 891–903.

    Article  PubMed  CAS  Google Scholar 

  85. Hirase, T., Staddon, J. M., Saitou, M., et al. (1997) Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110, 1603–1613.

    PubMed  CAS  Google Scholar 

  86. Haskins, J., Gu, L., Wittchen, E. S., Hibbard, J., and Stevenson, B. R. (1998) ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J. Cell Biol. 141, 199–208.

    Article  PubMed  CAS  Google Scholar 

  87. Stevenson, B. R., Siliciano, J. D., Mooseker, M. S., and Goodenough, D. A. (1986) Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J. Cell Biol. 103, 755–766.

    Article  PubMed  CAS  Google Scholar 

  88. Anderson, J. M. (1996) Cell signalling: MAGUK magic. Curr. Biol. 6, 382–384.

    Article  PubMed  CAS  Google Scholar 

  89. Watson, P. M. M., Anderson, J., VanItallie, C. M., and Doctrow, S. R. (1991) The tight junction-specific protein ZO-1 is a component of the human and rat blood-brain barrier. Neurosci. Letts. 129, 6–10.

    Article  CAS  Google Scholar 

  90. Yamamoto, T., Harada, N., Kano, K., et al. (1997) The Ras target AF-6 interacts with ZO-1 and serves as a peripheral component of tight junctions in epithelial cells. J. Cell Biol. 139, 785–795.

    Article  PubMed  CAS  Google Scholar 

  91. Satoh, H., Zhong, Y., Isomura, H., et al. Saitoh, M., Enomoto, K., Sawada, N., (1996) Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells. Exp. Cell Res. 222, 269–274.

    Article  PubMed  CAS  Google Scholar 

  92. Denker, B. M., and Nigam, S. K. (1998) Molecular structure and assembly of the tight junction. Am. J. Physiol. 274, F1–F9.

    PubMed  CAS  Google Scholar 

  93. Huber, J. D., Egleton, R. D., and Davis, T. P. (2001) Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. TINS, 24, 719–725.

    PubMed  CAS  Google Scholar 

  94. Cordenonsi, M., D’Atri, F., Hammar, E., Parry, D. A., Kendrick-Jones, J., Shore, D., and Citi, S. (1999) Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3, and myosin. J. Cell Biol. 147, 1569–1582.

    Article  PubMed  CAS  Google Scholar 

  95. Kuruganti, P. A., Hinojoza, J. R., Eaton, M. J., Ehmann, U. K., and Sobel, R. A. (2002) Interferon-β counteracts inflammatory mediator-induced effects on brain endothelial tight junction molecules—Implications for multiple sclerosis. J. Neuropathol. Exp. Neurol. 61, 710–724.

    PubMed  CAS  Google Scholar 

  96. Anderson, J. M., Stevenson, B. R., Jesaitis, L. A., Goodenough, D. A., and Mooseker, M. S. (1988) Characterization of ZO-1, a protein component of the tight junction from mouse liver and Madin-Darby canine kidney cells. J. Cell Biol. 106, 1141–1149.

    Article  PubMed  CAS  Google Scholar 

  97. Stevenson, B. R., Anderson, J. M., Goodenough, D. A., and Mooseker, M. S. (1988) Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. J. Cell Biol. 107, 2401–2408.

    Article  PubMed  CAS  Google Scholar 

  98. Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., and Tsukita, S. (1999) Direct binding of three tight junction associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J. Cell Biol. 147, 1351–1363.

    Article  PubMed  CAS  Google Scholar 

  99. Nag, S., Dinsdale, H. B., and Robertson, D. M. (1978) Cytoplasmic filaments in intracerebral cortical vessels. Ann. Neurol. 3, 555–559.

    Article  PubMed  CAS  Google Scholar 

  100. Nag, S. (1995) Role of the endothelial cytoskeleton in blood-brain barrier permeability to proteins. Acta Neuropathol. (Bed.) 90, 454–460.

    Article  CAS  Google Scholar 

  101. Pardridge, W. M., Nowlin, D. M., Choi, T. B., Yang, J., Calaycay, J., and Shively, J. E. (1989) Brain capillary 46,000 Dalton protein is cytoplasmic actin and is localized to endothelial plasma membrane. J. Cereb. Blood Flow Metab. 9, 675–680.

    PubMed  CAS  Google Scholar 

  102. Nusrat, A., Parkos, C. A., Verkade, P., et al. (2000) Tight junctions are membrane microdomains. J. Cell Sei. 113, 1771–1781.

    CAS  Google Scholar 

  103. Schlegel, A., and Lisanti, M. P. (2001) The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal transduction. Cytokine Growth Factor Rev. 12, 41–51.

    Article  PubMed  CAS  Google Scholar 

  104. Madara, J. L., Parkos, C, Colgan, S., Nusrat, A., Atisook, K., and Kaoutzani, P. (1992) The movement of solutes and cells across tight junctions. Ann. New York Acad. Sei. 664, 47–60.

    Article  CAS  Google Scholar 

  105. Gloor, S. M., Wachtel, M., Bolliger, M. F., Ishihara, H., Landmann, R., and Frei, K. (2001) Molecular and cellular permeability control at the blood-brain barrier. Brain Res. Rev. 36, 258–264.

    Article  PubMed  CAS  Google Scholar 

  106. Rubin, L. L., and Staddon, J. M. (1999) The cell biology of the blood-brain barrier. Annu. Rev. Neurosei. 22, 11–28.

    Article  CAS  Google Scholar 

  107. Takeichi, M. (1995) Morphogenetic roles of classic cadherins. Curr. Biol. 7, 619–627.

    CAS  Google Scholar 

  108. Lampugnani, M. G., and Dejana, E. (1997) Interendothelial junctions: structure, signalling and functional roles. Curr. Opin. Cell Biol. 9, 674–682.

    Article  PubMed  CAS  Google Scholar 

  109. Gumbiner, B. M. (1996) Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell 84, 345–357.

    Article  PubMed  CAS  Google Scholar 

  110. Staddon, J. M., Herrenknecht, K., Smales, C., and Rubin, L. L. (1995) Evidence that tyrosine phosphorylation may increase tight junction permeability. J. Cell Sei. 108, 606–619.

    Google Scholar 

  111. Schultze, C., Smales, C., Rubin, L. L., and Staddon, J. M. (1997) Lysophosphatidic acid increases tight junction permeability in cultured brain endothelial cells. J. Neurochem. 86, 991–1000.

    Google Scholar 

  112. Staddon, J. M., Smales, C., Schulze, C., Esch, F. S., and Rubin, L. L. (1995) p120, a p-120 related protein (p100) and the cadherin/catenin complex. J. Cell Biol. 130, 369–381.

    Article  PubMed  CAS  Google Scholar 

  113. Frøkjaer-Jensen, J. (1980) Three-dimensional organization of plasmalemmal vesicles in endothelial cells. An analysis by serial sectioning of frog mesenteric capillaries. J. Ultrastruc. Res. 73, 9–20.

    Article  Google Scholar 

  114. Nag, S., Robertson, D. M., and Dinsdale, H. B. (1979) Quantitative estimate of pinocytosis in experimental acute hypertension. Acta Neuropathol. (Berl.) 46, 107–116.

    Article  CAS  Google Scholar 

  115. Dux, E., and Joó, F. (1982) Effects of histamine on brain capillaries: fine structural and immunohistochemical studies after intracarotid infusion. Exp. Brain Res. 47, 252–258.

    Article  PubMed  CAS  Google Scholar 

  116. Stewart, P. A., Hayakawa, K., Farrell, C. L., and Del Maestro, R. F (1985) A quantitative study of blood-brain barrier permeability ultrastructure in a new rat glioma model. Acta Neuropathol. (Berl.) 67, 96–102.

    Article  CAS  Google Scholar 

  117. Stewart, P. A., Magliocco, M., Hayakawa, K., et al. (1987) A quantitative analysis of blood-brain barrier ultrastructure in the aging human. Microvasc. Res. 33, 270–282.

    Article  PubMed  CAS  Google Scholar 

  118. Coomber, B. L., and Stewart, P. A. (1985) Morphometric analysis of CNS microvascular endothelium. Microvasc. Res. 30, 99–115.

    Article  PubMed  CAS  Google Scholar 

  119. Stewart, P. A. (2000) Endothelial vesicles in the blood-brain barrier: are they related to permeability? Cell. Mol. Neurobiol. 20, 149–163.

    Article  PubMed  CAS  Google Scholar 

  120. Simionescu, N., Simionescu, M., and Palade, G. E. (1974) Morphometric data on the endothelium of blood capillaries. J. Cell Biol. 60, 128–152.

    Article  PubMed  CAS  Google Scholar 

  121. Coomber, B. L., Stewart, P. A., Hayakawa, E. M., Farrell, C. L., and Del Maestro, R. F. (1988) A quantitative assessment of microvessel ultrastructure in C6 astrocytoma spheroids transplanted to brain and muscle. J. Neuropath. Exp. Neurol. 47, 29–40.

    Article  PubMed  CAS  Google Scholar 

  122. Shea, S. M., and Raskova, J. (1983) Vesicular diffusion and thermal forces. Fed. Proc. 42, 2431–2434.

    PubMed  CAS  Google Scholar 

  123. Simionescu, M. (1988) Receptor-mediated transcytosis of plasma molecules by vascular endothelium. In Endothelial Cell Biology in Health and Disease. (Simionescu, N., and Simionescu, N., eds.) Plenum, New York,. pp. 69–104.

    Google Scholar 

  124. Schnitzer, J. E., Allard, J., and Oh, P. (1995) NEM inhibits transcytosis, endocytosis, and capillary permeability: Implications of caveolae fusion in endothelia. Am. J. Physiol. 268, H48–H55.

    PubMed  CAS  Google Scholar 

  125. Simionescu, M., Gafencu, A., and Antohe, F. (2002) Transcytosis of plasma macromolecules in endothelial cells: a cell biological survey. Microsc. Res. Tech. 57, 269–288.

    Article  PubMed  CAS  Google Scholar 

  126. Schnitzer, J. E. (2001) Caveolae: from basic trafficking mechanisms to targeting transcytosis for tissue-specific drug and gene delivery in vivo. Adv. Drug Delivery Rev. 49, 265–280.

    Article  CAS  Google Scholar 

  127. Palade, G. E., Simionescu, M., and Simionescu, N. (1979) Structural aspects of the permeability of the microvascular endothelium. Acta Physiol. Scand. 463, 11–32.

    CAS  Google Scholar 

  128. Predescu, D., and Palade, G. E. (1993) Plasmalemmal vesicles represent the large pore system of continuous microvascular endothelium. Am. J. Physiol. 265, H725–H733.

    PubMed  CAS  Google Scholar 

  129. Predescu, S. A., Predescu, D. N., and Palade, G. E. (1997) Plasmalemmal vesicles function as transcytotic carriers for small proteins in the continuous endothelium. Am. J. Physiol. 272, H937–H949.

    PubMed  CAS  Google Scholar 

  130. Simionescu, N., Simionescu, M., and Palade, G. E. (1975) Permeability of muscle capillaries to small hemepeptides. Evidence for the existence of patent transendothelial channels. J. Cell Biol. 64, 585–607.

    Article  Google Scholar 

  131. Nag, S. (1998) Blood-brain barrier premeability measured with histochemistry. In Introduction to the Blood-Brain Barrier. Methodology, Biology and Pathology. (Pardridge, W. M., ed.) Cambridge University Press, Cambridge, UK, pp. 113–121.

    Chapter  Google Scholar 

  132. Shivers, R. R., and Harris, R. J. (1984) Opening of the blood-brain barrier in Anolis Carolinenis. A high voltage electron microscope protein tracer study. Neuropathol. Appl. Neurobiol. 10, 343–356.

    Article  PubMed  CAS  Google Scholar 

  133. Anderson, R. G., Kamen, B. A., Rothberg, K. G., and Lacey, S. W. (1992) Potocytosis: sequestration and transport of small molecules by caveolae. Science 255, 410–411.

    Article  PubMed  CAS  Google Scholar 

  134. Anderson, R. G (1998) The caveolae membrane system. Annu. Rev. Biochem. 67, 199–225.

    Article  PubMed  CAS  Google Scholar 

  135. Fielding, C. J. (2001) Caveolae and signaling. Curr. Opin. Lipidol. 12, 281–287.

    Article  PubMed  CAS  Google Scholar 

  136. Fujimoto, T., Hagiwara, H., Aoki, T., Kogo, H., and Nomura, R. (1998) Caveolae: from a morphological point of view. J. Electron Microsc. 47, 451–460.

    CAS  Google Scholar 

  137. Michel, C. C. (1998) Capillaries, caveolae, calcium and cyclic nucleotides: a new look at microvascular permeability. J. Mol. Cardiol. 30, 2541–2546.

    Article  CAS  Google Scholar 

  138. Mukerjee, S., and Maxfield, F. R. (2000) Role of membrane organization and membrane domains in endocytic lipid trafficking. Traffic. 1, 203–211.

    Article  Google Scholar 

  139. Okamoto, T., Schlegel, A., Scherer, P. E., and Lisanti, M. P. (1998) Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J. Biol. Chem. 273, 5419–5422.

    Article  PubMed  CAS  Google Scholar 

  140. Shaul, P. W., and Anderson, R. J. (1998) Role of plasmalemmal caveolae in signal transduction. Am. J. Physiol. 275, L843–L851.

    PubMed  CAS  Google Scholar 

  141. Monier, S., Parton, R. G., Vogel, F., Behlke, J., Henske, A., and Kurzchalia, T (1995) VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerises in vivo and in vitro. Mol. Biol. Cell 6, 911–927.

    PubMed  CAS  Google Scholar 

  142. Rothberg, K. G., Heuser, J. E., Donzell, W. C, Ying, Y. S., Glenney, J. R., and Anderson, R. G. (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68, 673–682.

    Article  PubMed  CAS  Google Scholar 

  143. Scherer, P. E., Okamoto, T, Chun, M., Nishimoto, I., Lodish, H. F, and Lisanti, M. P. (1996) Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc. Natl. Acad. Sci. U.S.A. 93, 131–135.

    Article  PubMed  CAS  Google Scholar 

  144. Garcia-Cardena, G., Martasek, P., Masters, B. S., et al. (1997) Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. J. Biol. Chem. 272, 25,437–25,440.

    Article  PubMed  CAS  Google Scholar 

  145. Lui, P., and Anderson, R. G. W. (1995) Compartmentalized production of ceramide at the cell surface. J. Biol. Chem. 270, 27,179–27,185.

    Article  Google Scholar 

  146. Li, S., Couet, J., and Lisanti, M. P. (1996) Src tyrosine kinases, Ga subunits and H-ras share a common membrane-anchored scaffolding protein, caveolin: caveolin binding negatively regulates the autoactivation of Src tyrosine kinases. J. Biol. Chem. 271, 29,182–29,190.

    Article  PubMed  CAS  Google Scholar 

  147. Couet, J., Li, S., Okamoto, T., Scherer, P. E., and Lisanti, M. P. (1997) Molecular and cellular biology of caveolae paradoxes and elasticities. Trends Cardiovasc Med. 7, 102–110.

    Article  Google Scholar 

  148. Antohe, F., Heltianu, C., and Simionescu, M. (1991) Albumin binding proteins of endothelial cells: Immunocytochemical detection of the 18 kDa peptide. Eur. J. Cell Biol. 56, 34–42.

    PubMed  CAS  Google Scholar 

  149. Schnitzer, J. E. (1992) gp60 is an albumin-binding glycoprotein expressed by continuous endothelium involved in albumin transcytosis. Am. J. Physiol. 262, H246–H254.

    PubMed  CAS  Google Scholar 

  150. Fujimoto, T., Nakade, S., Miyawaki, K., and Ogawa, K. (1992) Localization of 1,4,5-triphosphate receptor-like protein in plasmalemmal caveolae. J. Cell Biol. 119, 1507–1513.

    Article  PubMed  Google Scholar 

  151. Fujimoto, T. (1993) Calcium pump of the plasma membrane is localized in caveolae. J. Cell Biol. 120, 1147–1157.

    Article  PubMed  CAS  Google Scholar 

  152. Kurzchalia, T. V., and Parton, R. G (1999) Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11, 424–431.

    Article  PubMed  CAS  Google Scholar 

  153. Stan, R.-V., Roberts, W. G., Predescu, D., et al. (1997) Immunoisolation and partial characterization of endothelial plasmalemmal vesicles (caveolae). Mol. Biol. Cell 8, 595–605.

    PubMed  CAS  Google Scholar 

  154. Stan, R.-V., Ghitescu, L., Jacobson, B. S., and Palade, G. E. (1999) Isolation, cloning, and localization of rat PV-1. A novel endothelial caveolar protein. J. Cell Biol. 145, 1189–1198.

    Article  PubMed  CAS  Google Scholar 

  155. Ghitescu, L. D., Crine, P., and Jacobson, B. S. (1997) Antibodies specific to the plasma membrane of rat lung microvascular endothelium. Exp. Cell Res. 232, 47–55.

    Article  PubMed  CAS  Google Scholar 

  156. Horvat, R., and Palade, G. E. (1993) Thrombomodulin and thrombin localization on vascular endothelium; their internalization and transcytosis by plasmalemmal vesicles. Eur. J. Cell Biol. 61, 299–313.

    PubMed  CAS  Google Scholar 

  157. Huang, C., Hepler, J. R., Chen, L. T., et al. (1997) Organization of G proteins and adenyl cyclase at the plasma membrane. Mol. Biol. Cell 8, 2365–2378.

    PubMed  CAS  Google Scholar 

  158. Henley, J. R., Krueger, E. W., Oswald, B. J., and McNiven, M. A. (1998) Dynamin-mediated internalization of caveolae. J. Cell Biol. 141, 85–99.

    Article  PubMed  CAS  Google Scholar 

  159. Oh, P., McIntosh, D. P., and Schnitzer, J. E. (1998) Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J. Cell Biol. 141, 101–114.

    Article  PubMed  CAS  Google Scholar 

  160. Shaul, P. W., Smart, E. J., Robinson, L., et al. (1996) Acylation targets endothelial nitric oxide synthase to plasmalemmal caveolae. J. Biol. Chem. 271, 6518–6522.

    Article  PubMed  CAS  Google Scholar 

  161. McIntosh, D. P., and Schnitzer, J. E. (1999) Caveolae require intact VAMP for targeted transport in vascular endothelium. Am. J. Physiol. 277, H2222–H2232.

    PubMed  CAS  Google Scholar 

  162. Schnitzer, J. E., Liu, J., and Oh, P. (1995) Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J. Biol. Chem. 270, 14,399–14,404.

    Article  PubMed  CAS  Google Scholar 

  163. Fra, A. M., Masserini, M., Palestini, P., Sonnino, S., and Simons, K. (1995) A photoreactive derivative of ganglioside GM1 specifically cross-links VIP21-caveolin on the cell surface. FEBS Lett. 375, 11–14.

    Article  PubMed  CAS  Google Scholar 

  164. Sargiacomo, M., Scherer, P. E., Tang, Z., et al. (1995) Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc. Natl. Acad. Sci. U.S.A. 92, 9407–9411.

    Article  PubMed  CAS  Google Scholar 

  165. Lisanti, M. P., Scherer, P. E., Vidugiriene, J., et al. (1994) Characterization of caveolinrich membrane domains isolated from an endothelial-rich source: Implications for human disease. J. Cell Biol. 126, 111–126.

    Article  PubMed  CAS  Google Scholar 

  166. Hay, J. C, and Schneller, R. H. (1997) SNAREs and NSF in targeted membrane fusion, Curr. Opin. Cell Biol. 9, 505–512.

    Article  PubMed  CAS  Google Scholar 

  167. Rothman, J. E. (1994) Intracellular membrane fusion. Adv. Second Mess. Phosphoprot. Res. 29, 81–96.

    CAS  Google Scholar 

  168. Couet, J., Belanger, M. M., Roussel, E., and Drolet, M.-C. (2001) Cell biology of caveolae and caveolin. Advanced Drug Delivery Reviews 49, 223–235.

    Article  PubMed  CAS  Google Scholar 

  169. Stan, R.-V. (2002) Structure and function of endothelial caveolae. Microsc. Res. Tech. 57, 350–364.

    Article  PubMed  Google Scholar 

  170. McIntosh, D. P., Tan, X.-Y., Oh, P., and Schnitzer, J. E. (2002) Targeting endothelium and its dynamic caveolae for tissue-specific transcytosis in vivo: A pathway to overcome cell barriers to drug and gene delivery. P.N.A.S. 99, 1996–2001.

    Article  PubMed  CAS  Google Scholar 

  171. Schubert, W., Frank, P. G., Razani, B., Park, D. S., Chow, C. W., and Lisanti, M. P. (2001) Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. J. Biol. Chem. 276, 48,619–48,622.

    Article  PubMed  CAS  Google Scholar 

  172. Schnitzer, J. (1998) Vascular targeting as a strategy for cancer therapy. New Engl. J. Med. 339, 472–474.

    Article  PubMed  CAS  Google Scholar 

  173. Oldendorf, W. H., and Brown, W. J. (1975) Greater number of capillary endothelial cell mitochondria in brain than muscle. Proc. Soc. Exp. Biol. Med. 149, 736–738.

    PubMed  CAS  Google Scholar 

  174. Oldendorf, W. H., Cornford, M. E., and Brown, W. J. (1977) The large apparent work capability of the blood-brain barrier: A study of mitochondrial content of capillary endothelial cells in brain and other tissues of the rat. Ann Neurol. 1, 409–417.

    Article  PubMed  CAS  Google Scholar 

  175. Claudio, L., Kress, Y., Norton, W. T, and Brosnan, C. F. (1989) Increased vesicular transport and decreased mitochondrial content in blood-brain barrier endothelial cells during experimental autoimmune encephalomyelitis. Am. J. Pathol. 135, 1157–1168.

    PubMed  CAS  Google Scholar 

  176. Hickey, W. F, Hsu, B. L., and Kimura, H. (1991) T-lymphocyte entry into the central nervous system. J. Neurosci. Res. 28, 254–260.

    Article  PubMed  CAS  Google Scholar 

  177. Hickey, W. F (2001) Basic principles of immunological surveillance of the normal central nervous system. Glia 36, 118–124.

    Article  PubMed  CAS  Google Scholar 

  178. Lossinsky, A. S., Buttle, K. F, Pluta, R., Mossakowski, M. J., and Wiśniewski, H. M. (1999) Immunoultrastructural expression of intercellular adhesion molecule-1 in endothelial cell vesiculotubular structures and vesiculovacuolar organelles in blood-brain barrier development and injury. Cell Tissue Res. 295, 77–88.

    Article  PubMed  CAS  Google Scholar 

  179. Washington, R., Burton, J., Todd, R. F III, Newman, W., Dragovic, L., and Dore-Duffy, P. (1994) Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann. Neurol. 35, 89–97.

    Article  PubMed  CAS  Google Scholar 

  180. Williams, K. C., Zhao, R. W., Ueno, K., and Hickey, W. F. (1996) PECAM-1 (CD31) expression in the central nervous system and its role in experimental allergic encephalomyelitis in the rat. J. Neurosci. Res. 45, 747–757.

    Article  PubMed  CAS  Google Scholar 

  181. Wong, D., and Dorovini-Zis, K. (1996) Regulation by cytokines and lipopolysaccharide of E-selectin expression by human brain microvessel endothelial cells in primary culture. J. Neuropathol. Exp. Neurol. 55, 225–235.

    Article  PubMed  CAS  Google Scholar 

  182. Easton, A. S., and Dorovini-Zis, K. (2001) The kinetics, function, and regulation of P-selectin expressed by human brain microvessel endothelial cells in primary culture. Microvasc. Res. 62, 335–345.

    Article  PubMed  CAS  Google Scholar 

  183. McCarron, R. M., Wang, I., Stanimirovic, D. B., and Spatz, M. (1995) Differential regulation of adhesion molecule expression by human cerebrovascular and umbilical vein endothelial cells. Endothelium 2, 339–346.

    Article  CAS  Google Scholar 

  184. Prat, A., Becher, B., Blain, M., and Antel, J. P. (1998) Induction of B7.1 and B7.2 co-stimulatory molecules on the surface of human brain endothelial cells. J. Neuroimmunol. 90, 24 (abstract).

    Google Scholar 

  185. Wong, D., and Dorovini-Zis, K. (1992) Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and liposaccharide. J. Neuroimmunol. 39, 11–21.

    Article  PubMed  CAS  Google Scholar 

  186. Wong, D., and Dorovini-Zis, K. (1995) Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. Microvasc. Res. 49, 325–339.

    Article  PubMed  CAS  Google Scholar 

  187. Bonecchi, R., Bianchi, G., Bordignon, P. P., et al. (1997) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J. Exp. Med. 187, 129–134.

    Article  Google Scholar 

  188. Borges, E., Tietz, W., Steegmaier, M., et al. (1997) P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds P-selectin and supports migration into inflamed skin. J. Exp. Med. 185, 573–578.

    Article  PubMed  CAS  Google Scholar 

  189. Eng, L. F., Ghirnikar, R. S., and Lee, Y. L. (1996) Inflammation in EAE: role of chemokine/cytokine expression by resident and infiltrating cells. Neurochem. Res. 21, 511–525.

    Article  PubMed  CAS  Google Scholar 

  190. Jourdan, P., Abbal, C., Nora, N., et al. (1998) IL-4 induces functional cell-surface expression of CXCR4 on human T cells. J. Immunol. 160, 4153–4157.

    PubMed  CAS  Google Scholar 

  191. Meeusen, E. N., Premier, R. R., and Brandon, M. R. (1996) Tissue-specific migration of lymphocytes: a key role for Th1 and Th2 cells? Immunol. Today. 17, 421–424.

    Article  PubMed  CAS  Google Scholar 

  192. Zach, O., Bauer, H. C, Richter, K., Webersinke, G., Tontsch, S., and Bauer, H. (1997) Expression of a chemotactic cytokine (MCP-1) in cerebral capillary endothelial cells. Endothelium 5, 143–153.

    Article  PubMed  CAS  Google Scholar 

  193. Andjelkovic, A. V., Spencer, D. D., and Pachter, J. S. (1999) Visualization of chemokine binding sites on human brain microvessels. J. Cell Biol. 145, 403–412.

    Article  PubMed  CAS  Google Scholar 

  194. Middleton, J., Neil, S., Wintle, J., et al. (1997) Transcytosis and surface presentation of IL-8 by venular endothelial cells. Cell 91, 385–395.

    Article  PubMed  CAS  Google Scholar 

  195. Berman, J. W., Guida, M. P., Warren, J., Amat, J., and Brosnan, C. F. (1996) Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J. Immunol. 156, 3017–3023.

    PubMed  CAS  Google Scholar 

  196. Biernacki, K., Prat, A., Pouly, S., Nalbantoglu, J., Couture, R., and Antel, J. P. (2000) Kinin B1 receptor expression and function on human brain endothelial cells: in vitro blood-brain barrier permeability study. Neurology 54, A167 (abstract).

    Google Scholar 

  197. Prat, A., Biernacki, K., Lavoie, J-F., Poirier, J., Duquette, P., and Antel, J. P. (2002) Migration of multiple sclerosis lymphocytes through brain endothelium. Arch. Neurol. 59, 391–397.

    Article  PubMed  Google Scholar 

  198. Zhang, W., Smith, C, Shapiro, A., Monette, R., Hutchison, J., and Stanimirovic, D. (1999) Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J. Neuroimmunol. 101, 148–160.

    Article  PubMed  CAS  Google Scholar 

  199. Prat, A., Biernacki, K., Wosik, K., and Antel, J. (2001) Glial cell influence on the human blood-brain barrier. Glia 36, 145–155.

    Article  PubMed  CAS  Google Scholar 

  200. Shukaliak, J. A., and Dorovini-Zis, K. (2000) Expression of beta-chemokine RANTES and MIP-1 beta by human brain microvessel endothelial cells in primary culture. J. Neuropathol. Exp. Neurol. 59, 339–352.

    PubMed  CAS  Google Scholar 

  201. Biernacki, K., Prat, A., Pouly, S., Nalbantoglu, J., Couture, R., and Antel, J. P. (2000) Kinin B1 receptor expression and function on human brain endothelial cells: in vitro blood-brain barrier permeability study. Neurology. 54, A167 (abstract).

    Google Scholar 

  202. Jemison, L. M., Williams, S. K., Lublin, F. D., Knobler, R. L., and Korngold, R. (1993) Interferon-gamma-inducible endothelial cell class II major histocompatibility complex expression correlates with strain-and site-specific susceptibility to experimental allergic encephalomyelitis. J. Neuroimmunol. 47, 15–22.

    Article  PubMed  CAS  Google Scholar 

  203. Etienne, S., Bourdoulous, S., Strosberg, A. D., and Couraud, P. O. (1999) MHC class II engagement in brain endothelial cells induces protein kinase A-dependent IL-6 secretion and phosphorylation of cAMP response element-binding protein. J. Immunol. 163, 3636–3641.

    PubMed  CAS  Google Scholar 

  204. McCarron, R. M., Spatz, M., and Cowan, E. P. (1991) Class II MHC antigen expression by cultured human cerebral vascular endothelial cells. Brain Res. 566, 325–328.

    Article  PubMed  CAS  Google Scholar 

  205. Nag, S., and Gupta, S. (1981) Demonstration of Fc receptor on cerebral endothelium. J. Neuropathol. Exp. Neurol. 40, 327.

    Article  Google Scholar 

  206. Schlachetzki, F., Zhu, C., and Pardridge, W. M. (2002) Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier. J. Neurochem. 81, 203–206.

    Article  PubMed  CAS  Google Scholar 

  207. Bär, T., and Wolff, J. R. (1972) The formation of capillary basement membranes during internal vascularization of the rat’s cerebral cortex. Z. Zellforsch. 133, 231–248.

    Article  PubMed  Google Scholar 

  208. Betz, A. L., and Goldstein, G. W. (1981) Developmental changes in metabolism and transport properties of capillaries isolated from rat brain. J. Physiol. (Lond.) 312, 365–376.

    CAS  Google Scholar 

  209. Herkin, R., Götz, W., and Thies, M. (1990) Appearance of laminin, heparin sulphate proteoglycan, and collagen type IV during initial stages of vascularization of the neuroepithelium of the mouse embryo. J. Anat. 169, 189–195.

    Google Scholar 

  210. Risau, W., and Lemmon, W. (1988) Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis. Dev. Biol. 125, 441–450.

    Article  PubMed  CAS  Google Scholar 

  211. Timpl, R., Rohde, H., Risteli, L., Ott, U., Robey, P. G, and Martin, G R. (1982) Laminin. Methods Enzymol. 82:Pt A, 831–838.

    Article  PubMed  CAS  Google Scholar 

  212. Timpl, R., Wiedemann, H., van Delden, V., Furthmayr, H., and Kuhn, K. (1981) A network model for the organization of type IV collagen molecules in basement membrane. Eur. J. Biochem. 120, 203–211.

    Article  PubMed  CAS  Google Scholar 

  213. Linker, A., Hovingh, P., Kanwar, Y. S., and Farquhar, M. G (1981) Characterization of heparan sulfate isolated from drug glomerular basement membranes. Lab. Invest. 44, 560–565.

    PubMed  CAS  Google Scholar 

  214. Timpl, R. (1994) Proteoglycans of basement membranes. EXS 70, 123–144.

    PubMed  CAS  Google Scholar 

  215. Hynes, R. O. (1986) Fibronectins. Sci. Am. 254, 42–51.

    Article  PubMed  CAS  Google Scholar 

  216. Timpl, R., Dziadek, M., Fujiwara, S., Nowack, H., and Wick, G. (1983) Nidogen: a new, self-aggregating basement protein. Eur. J. Biochem. 137, 455–465.

    Article  PubMed  CAS  Google Scholar 

  217. Carlin, B., Jaffe, R., Bender, B., and Chung, A. E. (1981) Entactin, a novel basal lamina-associated sulfated glycoprotein. J. Biol. Chem. 256, 5209–5214.

    PubMed  CAS  Google Scholar 

  218. Kefalides, N. A., Alper, R., and Clark, C. C. (1979) Biochemistry and metabolism of basement membranes. Int. Rev. Cytol. 61, 167–228.

    Article  PubMed  CAS  Google Scholar 

  219. Vorbrodt, A. W. (1993) Morphological evidence of the functional polarization of brain microvascular endothelium. In The Blood-Brain Barrier. Cellular and Molecular Biology. (Pardridge, W. M., ed.), Raven, New York, pp. 137–164.

    Google Scholar 

  220. Brightman, M. W., and Kaya, M. (2000) Permeable endothelium and the interstitial space of brain. Cell. Mol. Neurobiol. 20, 111–130.

    Article  PubMed  CAS  Google Scholar 

  221. Sims, D. E. (2000) Diversity within pericytes. Clin. Exp. Pharmacol. Physiol. 27, 842–846.

    Article  PubMed  CAS  Google Scholar 

  222. Thomas, W. E. (1999) Brain macrophages: on the role of pericytes and perivascular cells. Brain Res. Rev. 31, 42–57.

    Article  PubMed  CAS  Google Scholar 

  223. Sims, D. E. (1991) Recent advances in pericyte biology—Implications for health and disease. Can. J. Cardiol. 7, 431–443.

    CAS  Google Scholar 

  224. Pardridge, W. M. (1999) Blood-brain barrier biology and methodology. J. Neurovirol. 5, 556–569.

    Article  PubMed  CAS  Google Scholar 

  225. Rucker, H. K., Wynder, H. J., and Thomas, W. E. (2000) Cellular mechanisms of CNS pericytes. Brain Res. Bull. 51, 363–369.

    Article  PubMed  CAS  Google Scholar 

  226. Farrell, C. R., Stewart, P. A., Farrell, C. L., and Del Maestro, R. F. (1987) Pericytes in human cerebral microvasculature. Anat. Rec. 218, 466–469.

    Article  PubMed  CAS  Google Scholar 

  227. Cuevas, P., Gutierrez-Diaz, J. A., Reimers, D., Dujovny, M., Diaz, F. G., and Ausman, J. I. (1984) Pericyte endothelial gap junctions in human cerebral capillaries. Anat. Embryol. 170, 155–159.

    Article  PubMed  CAS  Google Scholar 

  228. Tilton, R. G., Kilo, C., Williamson, J. R., and Murch, D. W. (1979) Differences in pericyte contractile function in rat cardiac and skeletal muscle micro vasculatures. Microvasc. Res. 18, 336–352.

    Article  PubMed  CAS  Google Scholar 

  229. Wakui, S. M., Furusato, M., Hasumura, M., et al. (1989) Two-and three-dimensional ultra-structure of endothelium and pericyte interdigitations in capillary of human granulation tissue. J. Electron Microsc. 38, 136–142.

    CAS  Google Scholar 

  230. Courtoy, P. J., and Boyles, J. (1983) Fibronectin in the microvasculature: Localization in the pericyte-endothelial interstitium. J. Ultrastruct. Res. 83, 258–273.

    Article  PubMed  CAS  Google Scholar 

  231. Alliot, F, Rutin J., Leenen, P. J., and Pessac, B. (1999) Pericytes and periendothelial cells of brain parenchyma vessels co-express aminopeptidase N, aminopeptidase A and nestin. J. Neurosci Res. 58, 367–378.

    Article  PubMed  CAS  Google Scholar 

  232. Balabanov, R., and Dore-Duffy, P. (1998) Role of the CNS microvascular pericyte in the blood-brain barrier. J. Neurosci. Res. 53, 637–644.

    Article  PubMed  CAS  Google Scholar 

  233. Bandopadhyay, R., Orte, C., Lawrenson, J. G., Reid, A. R., De Silva, S., and Allt, G. (2001) Contractile proteins in pericytes at the blood-brain and blood-retinal barriers. J. Neurocytol. 30, 35–44.

    Article  PubMed  CAS  Google Scholar 

  234. Risau, W., Dingler, A., Albrecht, U., Dehouck, M. P., and Cecchelli, R. (1992) Blood-brain barrier pericytes are the main source of γ-glutamyltranspeptidase activity in brain capillaries. J. Neurochem. 58, 667–672.

    Article  PubMed  CAS  Google Scholar 

  235. Gradera, R. R., Munitz, E., and Martinez-Rodriguez, R. (1993) Electron microscopic localization of GABA and glutamic acid decarboxylase (GAD) in the cerebral capillaries and their microenvironment. Cell Mol. Biol. 39, 809–817.

    Google Scholar 

  236. Gerhart, D. Z., and Drewes, L. R. (1987) Butyrylcholinesterase in pericytes associated with canine brain capillaries. Cell Tissue Res. 247, 533–536.

    Article  PubMed  CAS  Google Scholar 

  237. Boado, R. J., and Pardridge, W. M. (1994) Differential expression of α-actin mRNA and immunoreactive protein in brain microvascular pericytes and smooth muscle cells. J. Neurosci. Res. 39, 430–435.

    Article  PubMed  CAS  Google Scholar 

  238. Herman, I. M., and D’Amore, P. A. (1985) Microvascular pericytes contain muscle and nonmuscle actins. J. Cell Biol. 101, 43–52.

    Article  PubMed  CAS  Google Scholar 

  239. Wallow, I. H., and Burnside, B. (1980) Actin filaments in retinal pericytes and endothelial cells. Invest. Ophthalmol. Vis. Sci. 19, 1433–1441.

    PubMed  CAS  Google Scholar 

  240. Chan, L. S., Li, W., Khatami, M., and Rockey, J. H. (1986) Actin in cultured bovine retinal capillary pericytes: Morphological and functional correlation. Exp. Eye Res. 43, 41–54.

    Article  PubMed  CAS  Google Scholar 

  241. Joyce, N. C., Haire, M. F., and Palade, G. E. (1985) Contractile proteins in pericytes. I. Immunoperoxidase localization of tropomyosin. J. Cell Biol. 100, 1379–1386.

    Article  PubMed  CAS  Google Scholar 

  242. Joyce, N. C, Haire, M. F., and Palade, G. E. (1985) Contractile proteins in pericytes. II. Immunocytochemical evidence for the presence of two isomyosins in graded concentrations. J. Cell Biol. 100, 1387–1395.

    Article  PubMed  CAS  Google Scholar 

  243. Ehler, E., Karlhuber, G., Bauer, H.-C, and Draeger, A. (1995) Heterogeneity of smooth muscle-associated proteins in mammalian brain microvasculature. Cell and Tissue Res. 279, 393–403.

    Article  CAS  Google Scholar 

  244. Kelley, C., D’Amore P. A., Hechtman, H. B., and Shepro, D. (1987) Microvascular pericyte contractility in vitro: Comparison with other cells of the vascular wall. J. Cell Biol. 104, 483–490.

    Article  PubMed  CAS  Google Scholar 

  245. Fujimoto, K. (1995) Pericyte-endothelial gap junctions in developing rat cerebral capillaries: A fine structural study. Anat. Rec. 242, 562–565.

    Article  PubMed  CAS  Google Scholar 

  246. Nehls, V., Denzer, K., and Drenckhahn, D. (1992) Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res. 270, 469–474.

    Article  PubMed  CAS  Google Scholar 

  247. Crocker, D. J., Murad, T. M., and Geer, J. C. (1970) Role of the pericyte in wound healing. Exp. Mol. Pathol. 13, 51–65.

    Article  PubMed  CAS  Google Scholar 

  248. Orlidge, A., and D’Amore, P. A. (1987) Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J. Cell Biol. 105, 1455–1462.

    Article  PubMed  CAS  Google Scholar 

  249. Yan, Q., and Sage, E. H. (1998) Transforming growth factor-beta1 induces apoptotic death in cultured retinal endothelial cells but not in pericytes: Association with decreased expression of p21waf1/cip1. J. Cell Biochem. 70, 70–83.

    Article  PubMed  CAS  Google Scholar 

  250. Hirshi, K. K., and D’Amore, P. A. (1997) Control of angiogenesis by pericytes: molecular mechnaisms and significance. EXS., 79, 419–428.

    Google Scholar 

  251. Watanabe, S., Morisaki, N., Tezuka, M., et al. (1997) Cultured retinal pericytes stimulate in vitro angiogenesis of endothelial cells through secretion of a fibroblast growth factorlike molecule. Atherosclerosis 130, 101–107.

    Article  PubMed  CAS  Google Scholar 

  252. Kim, Y., Imdad, R. Y, Stephenson, A. H., Sprague, R. S., and Lonigro, A. J. (1998) Vascular endothelial growth factor mRNA in pericytes is upregulated by phorbol myristate acetate. Hypertension 31, 511–515.

    PubMed  CAS  Google Scholar 

  253. Takagi, H., King, G. L., and Aiello, L. P. (1996) Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes. Diabetes 45, 1016–1023.

    Article  PubMed  CAS  Google Scholar 

  254. Antonelli-Orlidge, A., Smith, S. R., and D’Amore, P. A. (1989) Influence of pericytes on capillary endothelial cell growth. Am. Rev. Respir. Dis. 140, 1129–1131.

    PubMed  CAS  Google Scholar 

  255. Nomura, M., Yamagishi, S., Harada, S., et al. (1995) Possible participation of autocrine and paracrine vascular endothelial growth factors in hypoxia-induced proliferation of endothelial cells and pericytes. J. Biol. Chem. 270, 28,316–28,324.

    Article  PubMed  CAS  Google Scholar 

  256. Chakravarthy, U., Gardiner, T. A., Anderson, P., Archer, D. B., and Trimble, E. R. (1992) The effect of endothelin 1 on the retinal microvascular pericyte. Microvasc. Res. 43, 241–254.

    Article  PubMed  CAS  Google Scholar 

  257. Yamagishi, S., Hsu, C-C., Kobayashi, K, and Yamamoto, H. (1993) Endothelin I mediates endothelial cell-dependent proliferation of vascular pericytes. Biochem. Biophys. Res. Commun. 191, 840–846.

    Article  PubMed  CAS  Google Scholar 

  258. 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.

    Article  PubMed  CAS  Google Scholar 

  259. Beck, L., and D’Amore, P. A. (1997) Vascular development: Cellular and molecular regulation. FASEB J. 11, 365–373.

    PubMed  CAS  Google Scholar 

  260. Benjamin, L. E., Hemo, I., and Keshet, E. (1998) A plasticity window for blood vessel remodeling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125, 1591–1598.

    PubMed  CAS  Google Scholar 

  261. Baker, R. N., Cancilla, P. A., Pollock, P. S., and Frommes, S. P. (1971) The movement of exogenous protein in experimental cerebral edema. An electiron microscopic study after freeze injury. J. Neuropathol. Exp. Neurol. 80, 668–679.

    Article  Google Scholar 

  262. Cancilla, P. A., Baker, R. N., Pollock, P. S., and Frommes, B. S. (1972) The reaction of pericytes of the central nervous system to exogenous protein. Lab. Invest. 26, 376–383.

    PubMed  CAS  Google Scholar 

  263. van Deurs, B. (1976) Observations on the blood-brain barrier in hypertensive rats, with particular reference to phagocytic pericytes. J. Ultrastruct. Res. 56, 65–77.

    Article  PubMed  Google Scholar 

  264. Esiri, M. M., and McGee, J. (1986) Monoclonal antibody to macrophages (EBM/11) labels macrophages and microglial cells in human brain. J. Clin. Pathol. 39, 615–621.

    Article  PubMed  CAS  Google Scholar 

  265. Balabanov, R., Washington, R., Wagnerova, J., and Dore-Duffy, P. (1996) CNS microvascular pericytes express macrophage-like function, cell surface intergrin alphaM, and macrophage marker ED-2. Microvasc. Res. 52, 127–142.

    Article  PubMed  CAS  Google Scholar 

  266. Graeber, M. B., Streit, W. J., and Kreutzberg, G. W. (1989) Identity of ED2-positive perivascular cells in rat brain. J. Neurosci. Res. 22, 103–106.

    Article  PubMed  CAS  Google Scholar 

  267. Graeber, M. B., Streit, W. J., Buringer, D., Sparks, D. L., and Kreutzberg, G. W. (1992) Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. J. Neuropathol. Exp. Neurol. 51, 303–311.

    Article  PubMed  CAS  Google Scholar 

  268. Pardridge, W. M., Yang, J., Buciak, J., and Tourtellotte, W. W. (1989) Human brain microvascular DR-antigen. J. Neurosci. Res. 23, 337–341.

    Article  PubMed  CAS  Google Scholar 

  269. Mato, M., Ookawara, S., Sugamata, M., and Aikawa, E. (1984) Evidence for the possible function of the fluorescent granular perithelial cells in brain as scavengers of highmolecular-weight waste products. Experientia 40, 399–402.

    Article  PubMed  CAS  Google Scholar 

  270. Fujikawa, L. S., Reay, C., and Morin, M. E. (1989) Class II antigen on retinal vascular endothelium, pericytes, macrophages and lymphocytes of the rat. Invest. Ophthamol. Visual Sci. 30, 66–73.

    CAS  Google Scholar 

  271. Fabry, Z., Fitzsimmons, K. M., Herlein, J. A., Moninger, T. O., Dobbs, M. B., and Hart, M. N. (1993) Production of cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes. J. Neuroimmunol. 47, 23–34.

    Article  PubMed  CAS  Google Scholar 

  272. Dore-Duffy, P., Balabanov, R., Rafols, J., and Swanborg, R. (1996) The recovery period of acute experimental autoimmune encephalomyelitis in rats corresponds to development of endothelial cell unresponsiveness to interferon gamma activation. J. Neurosci. Res. 44, 223–234.

    Article  PubMed  CAS  Google Scholar 

  273. Fabry, Z., Sandor, M., Gajewski, T. F, et al. (1993b) Differential activation of Th1 and Th2 CD4+ cells by murine brain microvessel endothelial cells and smooth muscle/pericytes. J. Immunol. 151, 38–47.

    PubMed  CAS  Google Scholar 

  274. Allt, G., and Lawrenson, J. G. (2001) Pericytes: Cell biology and pathology. Cells Tissues Organs 169, 1–11.

    Article  PubMed  CAS  Google Scholar 

  275. Herman, I. M. (1995) Microvascular pericytes in development and disease. In The Blood-Brain Barrier. Cellular and Molecular Biology. Pardridge, W. M., ed. Raven, New York, pp. 127–135.

    Google Scholar 

  276. Williams, K., Alvarez, X., and Lackner, A. A. (2001) Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 36, 156–164.

    Article  PubMed  CAS  Google Scholar 

  277. Hickey, W. F, and Kimura, H. (1988) Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239, 290–292.

    Article  PubMed  CAS  Google Scholar 

  278. Lassmann, H., Schmied, M., Vass, K., and Hickey, W. F. (1993) Bone marrow derived elements and resident microglia in brain inflammation. Glia 7, 19–24.

    Article  PubMed  CAS  Google Scholar 

  279. Bauer, J., Huitinga, I., Zhao, W., Lassmann, H., Hickey, W. F., and Dijkstra, C. D. (1995) The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia 15, 437–446.

    Article  PubMed  CAS  Google Scholar 

  280. Kida, S., Cteart, P. V., Zhang, E. T., and Weller, R. O. (1993) Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol. (Berl.) 85, 646–652.

    Article  CAS  Google Scholar 

  281. Lassmann, H., Vass, K., Brunner, C., and Wisniewski, H. M. (1986) Peripheral nervous system lesions in experimental allergic encephalomyelitis. Ultrastructural distribution of T cells and Ia-antigen. Acta Neuropathol. (Berl.) 69, 193–204.

    Article  CAS  Google Scholar 

  282. Unger, E. R., Sung, J. H., Manivel, J. C., Chenggis, M. L., Blazar, B. R., and Krivit, W. (1993) Male donor-derived cells in the brain of female sex-mismatched bone marrow transplant recipients: A Y chromosome specific in situ hybridization study. J. Neuropathol. Exp. Neurol. 52, 460–470.

    Article  PubMed  CAS  Google Scholar 

  283. Hickey, W. F., Vass, K., and Lassman, H. (1992) Bone marrow derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J. Neuropathol. Exp. Neurol. 51, 246–256.

    Article  PubMed  CAS  Google Scholar 

  284. Dijkstra, C. D., Doop, E. A., Joling, P., and Kraal, G. (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54, 589–599.

    PubMed  CAS  Google Scholar 

  285. Ford, A. L., Goodsall, A. L., Hickey, W. F, and Sedgwick, J. D. (1995) Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J. Immunnol. 154, 4309–4321.

    CAS  Google Scholar 

  286. Flaris, N. A., Densmore, T. L., Molleston, M. C, and Hickey, W. F (1993) Characterization of microglia and macrophages in the central nervous system of rats: definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 7, 34–40.

    Article  PubMed  CAS  Google Scholar 

  287. Perry, V. H., Hume, D. A., and Gordon, S. (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15, 313–326.

    Article  PubMed  CAS  Google Scholar 

  288. Morimura, T., Neuchrist, C., Kitz, K., et al. (1990) Monocyte subpopulations in human gliomas: expression of Fc and complement receptors and correlation with tumor proliferation. Acta Neuropathol. (Berl.) 80, 287–294.

    Article  CAS  Google Scholar 

  289. Ulvestad, E., Williams, K., Mork, S., Antel, J., and Nyland, H. (1994) Phenotypic differences between human monocyte/macrophages and microglial cells studied in situ and in vitro. J. Neuropathol. Exp. Neurol. 53, 492–501.

    Article  PubMed  CAS  Google Scholar 

  290. Ulvestad, E., Williams, K., Vedeler, C, et al. (1994) Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of Ig G. J. Neurol. Sci. 121, 125–131.

    Article  PubMed  CAS  Google Scholar 

  291. Lassmann, H., Zimprich, F., Vass, K., and Hickey, W. F. (1991) Microglial cells are a component of the perivascular glia limitans. J. Neurosei. Res. 28, 236–243.

    Article  CAS  Google Scholar 

  292. Streit, W. J., Graeber, M. B., and Kreutzberg, G. W. (1989) Expression of Ia antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury. Exp. Neurol. 105, 115–126.

    Article  PubMed  CAS  Google Scholar 

  293. Streit, W. J., and Graeber, M. B. (1993) Heterogeneity of microglial and perivascular cell populations: insights gained from the facial nucleus paradigm. Glia 7, 68–74.

    Article  PubMed  CAS  Google Scholar 

  294. Williams, K., Barr-Or, A., Ulvestad, E., Olivier, A., Antel, J. P., and Yong, W. V. (1992) Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes. J. Neuropathol. Exp. Neurol. 51, 538–549.

    Article  PubMed  CAS  Google Scholar 

  295. Bö, L., Mork, S., Kong, P. A., Nyland, H., Pardo, C. A., and Trapp, B. D. (1994) Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. J. Neuroimmunol. 51, 135–146.

    Article  PubMed  Google Scholar 

  296. Ulvestad, E., Williams, K., Bo, L., Trapp, B., Antel, J., and Mork, S. (1994) HLA class II molecules (HLA-DR, DP, DQ) on cells in the human CNS studied in situ and in vitro. Immunology 82, 535–541.

    PubMed  CAS  Google Scholar 

  297. De Simone, R., Giampaolo, A., Giometto, B., et al. (1995) The costimulatory molecule B7 is expressed on human microglia in culture and in multiple sclerosis acute lesions. J. Neuropathol. Exp. Neurol. 54, 175–187.

    Article  PubMed  Google Scholar 

  298. Aloisi, F., Ria, F., and Adorini, L. (2000) Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol. Today 21, 141–147.

    Article  PubMed  CAS  Google Scholar 

  299. Williams, K., Ulvestad, E., and Antel, J. P. (1994) B7/BB-1 expression on adult human microglia studied in vitro and in situ. Eur. J. Immunol. 24, 3031–3037.

    Article  PubMed  CAS  Google Scholar 

  300. Streit, W. J., Graeber, M. B., and Kreutzberg, G. W. (1989) Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system. J. Neuroimmunol. 21, 117–123.

    Article  PubMed  CAS  Google Scholar 

  301. Franson, P. (1985) Quantitative electron microscopic observations on the non-neuronal cells and lipid droplets in the posterior funiculus of the cat after dorsal rhizotomy. J. Comp. Neurol. 231, 490–499.

    Article  PubMed  CAS  Google Scholar 

  302. Elmquist, J. K., Breder, C. D., Sherin, J. E., et al. (1997) Intravenous lipopolysaccharide induces cyclooxygenase 2-like immunoreactivity in rat brain perivascular microglia and meningeal macrophages. J. Comp. Neurol. 381, 119–129.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Neuropathology, University of Toronto, Toronto, Canada

    Sukriti Nag

  2. Toronto Western Research Institute, University Health Network, Toronto, Canada

    Sukriti Nag

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    Sukriti Nag

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    Sukriti Nag

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Nag, S. (2003). Morphology and Molecular Properties of Cellular Components of Normal Cerebral Vessels. In: Nag, S. (eds) The Blood-Brain Barrier. Methods in Molecular Medicine™, vol 89. Humana Press. https://doi.org/10.1385/1-59259-419-0:3

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