The Blood-Brain Barrier

  • William H. Oldendorf


The concept of a barrier restricting exchange of certain tracer substances between blood and brain (the blood-barrier, BBB) originated with Paul Ehrlich’s observation in the 1880’s that intravenously injected aniline dyes failed to distribute to brain, whereas all other tissues were quickly colored. In general, it is the extracellular fluid (ECF) to which such dyes distribute to color the tissues. The blood plasma is a rapidly circulating subcompartment serving to disperse any local concentration of solute throughout the entire ECF. It can carry out this homogenizing function because of the ubiquity and permeability of capillaries. These capillary characteristics, together with the movement of blood plasma, bring the effective distances that solutes are required to diffuse between various body cells down to a few micrometers.


Monocarboxylic Acid Mitochondrial Content Tritiated Water Arachnoid Membrane Brain Capillary Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wislocki, G. B., and King, L. S., 1936, Am. J. Anat. 58:421–472.CrossRefGoogle Scholar
  2. 2.
    Saunders, N. R., 1977, Exp. Eye Res. 25:(Suppl.):523–550.PubMedCrossRefGoogle Scholar
  3. 3.
    Braun, L. D., Cornford, E. M., and Oldendorf, W. H., 1980, J. Neurochem. 34(1):147–152.PubMedCrossRefGoogle Scholar
  4. 4.
    Landis, E. M., and Pappenheimer, J. R., 1963, Handbook of Physiology, Volume 11 (W. F. Hamilton, ed.), American Physiological Society, Washington, pp. 961–1074.Google Scholar
  5. 5.
    Brightman, M. W., and Reese, T. S., 1969, J. Cell Biol. 40:648–677.PubMedCrossRefGoogle Scholar
  6. 6.
    Crone, C., and Thompson, A. H., 1970, Capillary Permeability (C. Crone and N. Lassen, eds.), Academic Press, New York, pp. 447–453.Google Scholar
  7. 7.
    Krogh, A., 1946, Proc. R. Soc. (Lond.)[Biol.] 234:171–177.Google Scholar
  8. 8.
    Siesjo, B. K., 1978, Brain Energy Metabolism, John Wiley & Sons, New York.Google Scholar
  9. 9.
    Bradbury, M. W. B., 1979, The Concept of a Blood-Brain Barrier, John Wiley & Sons, New York.Google Scholar
  10. 10.
    Bito, L. Z., Davson, H., and Fenstermacher, J. D. (eds.), 1977, Experimental Eye Research: The Ocular and Cererospinal Fluids, Volume 25, Supplement, Academic Press, New York.Google Scholar
  11. 11.
    Pardridge, W. M., and Mietus, L. J., 1979, J. Clin. Invest. 64(1): 145–154.PubMedCrossRefGoogle Scholar
  12. 12.
    Oldendorf, W. H., 1974, Proc. Soc. Exp. Biol. Med. 147(3):813–816.PubMedGoogle Scholar
  13. 13.
    Oldendorf, W. H., 1974, Annu. Rev. Pharmacol. 14:239–248.CrossRefGoogle Scholar
  14. 14.
    Collander, R., 1937, Trans. Faraday Soc. 33:985–990.CrossRefGoogle Scholar
  15. 15.
    Daniel, P. M., Donaldson, J., and Pratt, O. E., 1974, J. Physiol. (Lond.)237:8P–9P.Google Scholar
  16. 16.
    Chinard, F. P., Vosburgh, G. J., and Enns, T., 1955, Am. J. Physiol. 183:221–234.PubMedGoogle Scholar
  17. 17.
    Crone, C., 1963, Acta Physiol. Scand. 58:292–305.PubMedCrossRefGoogle Scholar
  18. 18.
    Oldendorf, W. H., 1981, Res. Methods Neurochem. 5:91–112.Google Scholar
  19. 19.
    Lassen, N. A., Trap-Jensen, J., Alexander, S. C., Olesen, J., and Paulson, O. B., 1971, Am. J. Physiol. 220(6):1627–1633.PubMedGoogle Scholar
  20. 20.
    Oldendorf, W. H., 1970, Brain Res. 24:372–376.PubMedCrossRefGoogle Scholar
  21. 21.
    Oldendorf, W. H., and Szabo, J., 1976, Am. J. Physiol. 230(1):94–98.PubMedGoogle Scholar
  22. 22.
    Raichle, M. E., Eichling, J. O., Straatmann, M. G., Welch, M. J., Larson, K. B., and Ter-Pogossian, M. M., 1976, Am. J. Physiol. 230:543–552.PubMedGoogle Scholar
  23. 23.
    Raichle, M. E., Hartman, B. K., Eichling, J. O., and Sharpe, L. G., 1975, Proc. Natl. Acad. Sci. U.S.A. 72(9):3726–3730.PubMedCrossRefGoogle Scholar
  24. 24.
    Preskorn, S. H., Hartman, B. K., Raichle, M. E., and Clark, H. B., 1980, J. Pharmacol. Exp. Ther. 231(2):313–320.Google Scholar
  25. 25.
    Oldendorf, W. H., Hyman, S., Braun, L., and Oldendorf, S. Z., 1972, Science 178:984–986.PubMedCrossRefGoogle Scholar
  26. 26.
    Oldendorf, W. H., 1971, Eur. Neurol. 6:49–55.PubMedCrossRefGoogle Scholar
  27. 27.
    Harper, N. J., 1959, J. Med. Pharm. Chem. 1:467–500.PubMedCrossRefGoogle Scholar
  28. 28.
    Creveling, C. R., Daly, J. W., Tokuyama, T., and Witkop, B., 1969, Experientia 25:26–27.PubMedCrossRefGoogle Scholar
  29. 29.
    Pardridge, W. M., Connor, J. D., and Crawford, I. L., 1975, CRC Crit. Rev. Toxicol. 3(2): 159–199.PubMedCrossRefGoogle Scholar
  30. 30.
    Crone, C., 1965, J. Physiol. (Lond.) 181:103–113.Google Scholar
  31. 31.
    Oldendorf, W. H., 1973, Am. J. Physiol. 224:1450–1453.PubMedGoogle Scholar
  32. 32.
    Richter, J. J., and Wainer, A., 1971, J. Neurochem. 18:613–620.PubMedCrossRefGoogle Scholar
  33. 33.
    Cornford, E. M., and Oldendorf, W. H., 1975, Biochim. Biophys. Acta 394(2):211–219.PubMedCrossRefGoogle Scholar
  34. 34.
    Oldendorf, W. H., and Braun, L. D., 1976, Brain Res. 113(1):219–224.PubMedCrossRefGoogle Scholar
  35. 35.
    Pardridge W. M., 1979, Endocrinology 105(3):605–612.PubMedCrossRefGoogle Scholar
  36. 36.
    Oldendorf, W. H., 1971, Am. J. Physiol. 221(6):1629–1639.PubMedGoogle Scholar
  37. 37.
    Pardridge, W. M., and Oldendorf, W. H., 1975, Biochim. Biophys. Acta 382:377–392.PubMedCrossRefGoogle Scholar
  38. 38.
    Crane, P. D., 1983, J. Neurochem. 40:160–167.PubMedCrossRefGoogle Scholar
  39. 39.
    Bradbury, M. W. B., Patlak, C. S., and Oldendorf, W. H., 1975, Am. J. Physiol. 229(4):1110–1115.PubMedGoogle Scholar
  40. 40.
    Steinwall, O., and Klatzo, I., 1966, J. Neuropathol. Exp. Neurol. 25:542–559.PubMedCrossRefGoogle Scholar
  41. 41.
    Pardridge, W. M., 1976, J. Neurochem. 27(1):333–335.PubMedCrossRefGoogle Scholar
  42. 42.
    Gjedde, A., and Crone, C., 1975, Am. J. Physiol. 229(5): 1165–1169.PubMedGoogle Scholar
  43. 43.
    Oldendorf, W. H., Braun, L. D., and Cornford, E. M., 1979, Stroke 10(5):577–581.PubMedCrossRefGoogle Scholar
  44. 44.
    Oldendorf, W. H., 1973, Am. J. Physiol. 224:967–969.PubMedGoogle Scholar
  45. 45.
    Oldendorf, W. H., Sisson, W. B., and Silverstein, A., 1971, Arch. Neurol. 24:524–528.PubMedCrossRefGoogle Scholar
  46. 46.
    Oldendorf, W. H., Sisson, W. B., Mehta, A. C., and Treciokas, L., 1971, Arch. Neurol. 24:423–430.PubMedCrossRefGoogle Scholar
  47. 47.
    Oldendorf, W. H., 1973, Arch. Neurol. 28:45–48.PubMedCrossRefGoogle Scholar
  48. 48.
    Oldendorf, W. H., 1971, Proc. Soc. Exp. Biol. Med. 136:385–386.PubMedGoogle Scholar
  49. 49.
    Christensen, N. H., 1969, Adv. Enzymol. 32:1–20.PubMedGoogle Scholar
  50. 50.
    Diamond, I., 1971, Arch. Neurol. 24:333–339.PubMedCrossRefGoogle Scholar
  51. 51.
    Oldendorf, W. H., and Brown, W. J., 1975, Proc. Soc. Exp. Biol. Med. 149(3):736–738.PubMedGoogle Scholar
  52. 52.
    Oldendorf, W. H., Cornford, M. E., and Brown, W. J., 1977, Ann. Neurol. 1(5):409–417.PubMedCrossRefGoogle Scholar
  53. 53.
    Ahmed, N., and Van Harreveld, A., 1969, J. Physiol. (Lond.) 204:31–50.Google Scholar
  54. 54.
    Davson, H., and Hollingsworth, J. R., 1973, J. Physiol. (Lond.) 233:327–347.Google Scholar
  55. 55.
    Meek, J. L., and Neff, N. H., 1973, Neuropharmacology 12:497–499.PubMedCrossRefGoogle Scholar
  56. 56.
    Wolfson, L. I., Katzman, R., and Escriva, A., 1974, Neurology (Minneap.) 24:772–779.CrossRefGoogle Scholar
  57. 57.
    Bradbury, M. W. B., 1971, Ion Homeostasis of the Brain (B. K. Siesjo and S. C. Sorensen, eds.), Munksgaard, Copenhagen, pp. 138–153.Google Scholar
  58. 58.
    Bradbury, M. W. B., and Sorno, G. S., 1977, Exp. Eye Res. 25(Suppl.):249–257.PubMedCrossRefGoogle Scholar
  59. 59.
    Rapoport, S. I., 1970, Am. J. Physiol. 219:270–274.PubMedGoogle Scholar
  60. 60.
    Rapoport, S. I., 1976, Blood-Brain Barrier in Physiology and Medicine, Raven Press, New York.Google Scholar
  61. 61.
    Rapoport, S. I., 1977, Exp. Eye Res. 25(Suppl.):499–509.PubMedCrossRefGoogle Scholar
  62. 62.
    Rapoport, S. I., Thompson, H. K., and Bidinger, J. M., 1974, Acta Radiol. 15:21–32.Google Scholar
  63. 63.
    Rapoport, S. I., and Thompson, H. K., 1973, Science 180:971.PubMedCrossRefGoogle Scholar
  64. 64.
    Davson, H., and Oldendorf, W. H., 1967, Proc. R. Soc. Med. 60:326–329.PubMedGoogle Scholar
  65. 65.
    Stewart, P. A., and Wiley, M. J., 1981, Dev. Biol. 84(1):183–192.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • William H. Oldendorf
    • 1
    • 2
    • 3
  1. 1.VA Medical CenterLos AngelesUSA
  2. 2.Departments of Neurology and PsychiatryUniversity of CaliforniaLos AngelesUSA
  3. 3.School of MedicineLos AngelesUSA

Personalised recommendations