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Quantitation of Blood-Brain Barrier Permeability

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Book cover Implications of the Blood-Brain Barrier and Its Manipulation

Abstract

The rate of uptake of most hydrophilic solutes into brain is limited by transport across the blood-brain barrier (BBB).11,97 The barrier between blood and brain extracellular fluid is located at the cerebral capillary endothelium, whereas the barrier between blood and cerebrospinal fluid (CSF) is located at the choroid plexus epithelium and the arachnoid membrane (Fig. 1). Morphologic evidence has established that the barrier at each site is formed by a single layer of cells that are joined by tight junctions (zonulae occludens).15,102 The cerebral capillaries, which comprise more than 95% of the total surface area of the BBB, represent the principal route for the entry of most solutes into the central nervous system (CNS).

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Abbreviations

Bi :

plasma concentration coefficient for elimination of tracer from plasma (dpm/ml)

bi :

rate coefficient for elimination of tracer from plasma (sec-1)

BUI:

brain uptake index

bi :

rate coefficient for elimination of tracer from plasma (sec-1)

BUI:

brain uptake index

CA :

tracer concentration in arterial blood or plasma (dpm/ml)

CB :

tracer concentration in arterial blood (dpm/ml)

Cp :

tracer concentration in arterial plasma

C:

mean concentration (dpm/ml)

Cp :

tracer concentration in arterial plasma

Cpf :

tracer concentration in perfusion fluid (dpm/ml)

C’:

ratio of tracer concentration in venous blood to that in injectate

CV :

tracer concentration in venous blood or plasma (dpm/ml)

E:

extraction

Eo :

unidirectional extraction

f:

correction factor for the difference between brain Hct and large blood-vessel Hct

F:

cerebral blood flow (ml/sec per g, also expressed in ml/min per 100g)

h(t):

transport function that describes the fraction of the indicator injected at the inflow at t=0 which arrives at the outflow at time t (sec-1

Hct:

Hematocrit

IF:

integration factor, defined as ∫Cp dt/[Cp(T)T] (sec)

Kin :

unidirectional transfer coefficient for influx into brain (ml/sec per g, also expressed as ml/min per 100g)

Kout :

unidirectional transfer coefficient for tracer efflux from brain (ml/sec per g, also expressed as ml/min per 100g)

kout :

rate coefficient for tracer loss from brain (sec-1) (note:kout=Kout/Vbr)

Km :

Michaelis constant, defined as that concentration of solute which gives one-half the maximal transport rate (μmol.ml)

Kd :

constant of nonsaturable diffusion (ml/sec/per g)

P:

cerebrovascular permeability (cm/sec)

PS:

cerebrovascular permeability-surface area product (ml/sec per g)

qbr :

quantity of tracer in brain parenchyma i.e. that which has crossed the blood-brain and is present in extravascular brain tissue (dpm/g) (also designated as M, A, Q, or C in the BBB literature)

qtot :

total quantity of tracer in brain including tracer in brain endothelial cells and tracer in residual blood (dpm/g)

r:

ratio of tracer concentrations in blood and plasma

S:

capillary surface area (cm2/g)

t:

time after injection of tracer (sec)

T:

time of uptake when brain tracer content is determined (sec)

T’:

time when brain tracer content is maximum (sec)

t1/2 :

half-time (sec, min, or hr)

Vbr :

physical distribution volume of tracer in brain, such as brain extracellular-fluid volume or brain-water volume (ml/g)

V ’br :

effective distribution volume of tracer in brain, defined as K in/k out (ml/g)

VB :

volume of blood in brain tissue (ml/g)

Vp :

volume of plasma in brain tissue (ml/g)

Vmax :

maximal rate of saturable transport (μmol/sec per g)

v:

fractional distribution volume of tracer in blood (ml/ml)

References

  1. Amtorp I: Estimation of capillary permeability of inulin, sucrose and mannitol in the rat brain cortex. Acta Physiol Scand 110:337–342, 1980.

    PubMed  CAS  Google Scholar 

  2. Bachelard HS, Daniel PM, Love ER, et al: The transport of glucose into the brain of the rat in vivo. Proc R Soc Lond B 183:71–82, 1973.

    PubMed  CAS  Google Scholar 

  3. Bass L, Robinson PJ: Capillary permeability of heterogeneous organs: A parsimonious interpretation of indicator diffusion data. Clin Exp Pharmacol Physiol 9:363–388, 1982.

    PubMed  CAS  Google Scholar 

  4. Bassingthwaighte JB, Chinard FP, Crone C, et al: Terminology for mass transport and exchange. Am J Physiol 250:H539–H545, 1986.

    PubMed  CAS  Google Scholar 

  5. Betz AL, Iannotti F: Simultaneous determination of regional cerebral blood flow and blood-brain glucose transport kinetics in the gerbil. J Cereb Blood Flow Metab 3:193–199, 1983.

    PubMed  CAS  Google Scholar 

  6. Blasberg RG, Fenstermacher JD, Patlak CS: Transport of a-aminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow Metab 3:8–32, 1983.

    PubMed  CAS  Google Scholar 

  7. Blasberg RG, Hiraga S, Nakagawa H, et al: Diffusion of AIB into brain from the CSF-brain interface: Influence on the calculated influx constants across brain capillaries. Acta Neurol Scand 72:91, 1985.

    Google Scholar 

  8. Blasberg RG, Kobayashi T, Patlak CS, et al: Regional blood flow, capillary permeability, and glucose utilization in two brain tumor models: Preliminary observations and pharmacokinetic implications. Cancer Treatm Rep 65:3–12, 1981.

    CAS  Google Scholar 

  9. Blasberg RG, Patlak CS, Fenstermacher JD, et al: Selection of experimental conditions for the accurate determination of blood-brain transfer constants from single-time experiments: A theoretical analysis. J Cereb Blood Flow Metab 3:215–225, 1983.

    PubMed  CAS  Google Scholar 

  10. Bradbury MWB: Ontogeny of mammalian brain barrier systems. In Cserr H, Fenstermacher JD, Fencl V (eds): Fluid Environment of the Brain. Academic, New York, 1975, pp. 81–103.

    Google Scholar 

  11. Bradbury M: The Concept of a Blood–Brain Barrier. Wiley, Chirchester, 1979.

    Google Scholar 

  12. Bradbury MWB, Kleeman CR: Stability of the potassium content of cerebrospinal fluid and brain. Am J Physiol 213:519–528, 1967.

    PubMed  CAS  Google Scholar 

  13. Bradbury MWB, Patlak CS, Oldendorf WH: Analysis of brain uptake and loss of radiotracers after intracarotid injection. Am J Physiol 229:1110–1115, 1975.

    PubMed  CAS  Google Scholar 

  14. Braun LD, Miller LP, Pardridge WM, et al: Kinetics of regional blood-brain barrier glucose transport and cerebral blood flow determined with the carotid injection technique in conscious rats. J Neurochem 44:911–915, 1985.

    PubMed  CAS  Google Scholar 

  15. Brightman MW, Reese TS: Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:648–677, 1969.

    PubMed  CAS  Google Scholar 

  16. Brooks DJ, Beaney RP, Lammertsma AA, et al: Quantitative measurement of blood-brain barrier permeability using rubidium-82 and positron emission tomography. J Cereb Blood Flow Metab 4:535–545, 1984.

    PubMed  CAS  Google Scholar 

  17. Brooks DJ, Beaney RP, Lammertsma AA, et al: Glucose transport across the blood-brain barrier in normal human subjects and patients with cerebral tumours studied using [11C]-3-0-methyl-D-glucose and positron emission tomography. J Cereb Blood Flow Metab 6:230–239, 1986.

    PubMed  CAS  Google Scholar 

  18. Bustany P, Henry JF, de Rotrou J, et al: Correlations between clinical state and positron emission tomography measurement of local braIn proteIn synthesis In Alzheimer’s dementia, Parkinson’s disease, schizophrenia and gliomas, In Greitz T, Ingvar DH, Widen L (eds): The Metabolism of the Human Brain Studied with Positron Emission Tomography. Raven, New York, 1985, pp. 241–249.

    Google Scholar 

  19. Collins JM, Dedrick RL: Distributed model for drug delivery to CSF and brain tissue. Am J Physiol 245.R303–R310, 1983.

    PubMed  CAS  Google Scholar 

  20. Cornford EM, Braun LD, Oldendorf WH, et al: Comparison of lipid-mediated blood-brain barrier penetrability in neonates and adults. Am J Physiol 243:C161–C168, 1982.

    PubMed  CAS  Google Scholar 

  21. Cremer JE, Seville MP: Regional brain blood flow, blood volume and haematocrit values in the adult rat. J Cereb Blood Flow Metab 3:254–256, 1983.

    PubMed  CAS  Google Scholar 

  22. Crone C: The permeability of capillaries in various organs as determined by use of the indicator diffusion method. Acta Physiol Scand 58:292–305, 1963.

    PubMed  CAS  Google Scholar 

  23. Crone C: The permeability of brain capillaries to non-electrolytes. Acta Physiol Scand 64:407–417,1965.

    PubMed  CAS  Google Scholar 

  24. Crone C: Capillary permeability—techniques and problems, In Crone C, Lassen NA (eds): Capillary Permeability, Academic, New York, 1970, pp. 15–31.

    Google Scholar 

  25. Crone C, Levitt DG: Capillary permeability to small solutes, In Renkin EM, Michel CC, (eds): Handbook of Physiology. Section 2: The Cardiovascular System. Vol. 4: Microcirculation. Part 1. American Physiological Society, Bethesda, 1984, pp. 411–466, 1984.

    Google Scholar 

  26. Daniel PM, Pratt OE, Wilson PA: The transport of L-leucine into the brain of the rat in vivo: Saturable and non-saturable components of influx. Proc R Soc Lond B 196:333–346, 1977.

    PubMed  CAS  Google Scholar 

  27. Davson H: A comparative study of the aqueous humor and cerebrospinal fluid in the rabbit. J Physiol (Lond) 129:111–133, 1955.

    CAS  Google Scholar 

  28. Davson H, Welch K: The permeation of several materials into the fluids of the rabbit’s brain. J Physiol (Lond) 218:337–351, 1971.

    CAS  Google Scholar 

  29. Draper N, Smith H: Applied Regression Analysis, 2nd Ed. Wiley, New York, 1981, pp. 458–517.

    Google Scholar 

  30. Eichling JOM, Raichle ME, Grubb RL, et al: Evidence of the limitations of water as a freely diffusible tracer in brain of the rhesus monkey. Circ Res 35:358–364, 1974.

    PubMed  CAS  Google Scholar 

  31. Fenstermacher JD, Blasberg RG, Patlak CS: Methods for quantifying the transport of drugs across brain barrier systems. Pharmacol Ther 14:217–248, 1981.

    PubMed  CAS  Google Scholar 

  32. Fenstermacher JD, Rapoport SI: Blood–brain barrier. In Renkin EM, Michel CC (eds): Handbook of Physiology. Section 2: The Cardiovascular System. Vol. 4: Microcirculation. Part 2. American Physiological Society, Bethesda, 1984, pp. 969–1000.

    Google Scholar 

  33. Frackowiak RSJ, Lenzi GL, Jones T, et al: Quantitative measurement of regional blood flow and oxygen metabolism in man using 1 50 and positron emission tomography: Theory, procedure, and normal values. J Comput Assist Tomogr 4:727–736, 1980.

    PubMed  CAS  Google Scholar 

  34. Fuglsang A, Lomholt M, Gjedde A: Blood–brain transfer of glucose and glucose analogs in newborn rats. J Neurochem 46:1417–1428, 1986.

    PubMed  CAS  Google Scholar 

  35. Gilboe DD: Perfusion of the isolated brain, In Lajtha A (ed): Handbook of Neurochemistry. Vol. 2. Plenum, New York, 1982, pp. 301–330.

    Google Scholar 

  36. Gjedde A: Rapid steady state analysis of blood-brain glucose transfer in rat. Acta Physiol Scand 108:331– 339, 1980.

    PubMed  CAS  Google Scholar 

  37. Gjedde A: High and low-affinity transport of D-glucose from blood to brain. J Neurochem 36:1463–1471, 1981.

    PubMed  CAS  Google Scholar 

  38. Gjedde A: Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: A re-examination. Brain Res Rev 4:237–274, 1982.

    CAS  Google Scholar 

  39. Gjedde A, Diemer NH: Double-tracer study of the fine regional blood–glucose transfer in the rat by computer assisted autoradiography. J Cereb Blood Flow Metab 5:282–289, 1985.

    PubMed  CAS  Google Scholar 

  40. Gjedde A, Rasmussen M: Blood–brain glucose transport in the conscious rat: Comparison of the intravenous and intracarotid injection methods. J Neurochem 35:1375–1381, 1980.

    PubMed  CAS  Google Scholar 

  41. Gjedde A, Weinhard K, Heiss WD, et al: Comparative regional analysis of 2-fluorodeoxyglucose and methylglucose uptake in brain of four stroke patients. With special reference to the regional estimation of lumped constant. J Cereb Blood Flow Metab 5:163–178, 1985.

    PubMed  CAS  Google Scholar 

  42. Goldstein GW, Betz AL, Bowman PD: Use of isolated brain capillaries and cultured endothelial cells to study the blood-brain barrier. Fed Proc 43:191–195, 1984.

    PubMed  CAS  Google Scholar 

  43. Granger DN, Perry MA: Permeability characteristics of the microcirculation, In Mortillaro NA (ed): The Physiology and Pharmacology of the Microcirculation, Vol. 1. Academic, New York, 1983, pp. 157–208.

    Google Scholar 

  44. Greenwood J, Luthert PJ, Pratt OE, et al: Maintenance of the integrity of the blood-brain barrier in the rat during an in situ saline-based perfusion. Neurosci Lett 56:223–227, 1985.

    PubMed  CAS  Google Scholar 

  45. Hardebo JE, Nilsson B: Estimation of cerebral extraction of circulating compounds by the brain uptake index method: Influence of circulation time, volume injection, and cerebral blood flow. Acta Physiol Scand 107:153–159, 1979.

    PubMed  CAS  Google Scholar 

  46. Hasegawa H, Yuritaka U, Hayakawa T, et al: Changes of the blood-brain barrier in experimental metastatic brain tumors. J Neurosurg 59:304–310, 1983.

    PubMed  CAS  Google Scholar 

  47. Hawkins RA, Mans AM, Biebuyck JF: Amino acid supply to individual cerebral structures in awake and anesthetized rats. Am J Physiol 242:E1–E11, 1982.

    PubMed  CAS  Google Scholar 

  48. Hawkins RA, Phelps ME, Huang SC, et al: A kinetic evaluation of blood-brain barrier permeability in human brain tumors with 68Ga-EDTA and positron computed tomography. J Cereb Blood Flow Metab 4:507–515, 1984.

    PubMed  CAS  Google Scholar 

  49. Hertz MM, Bolwig TG: Blood–brain barrier studies in the rat: An indicator dilution technique with tracer sodium as an internal standard for estimation of extracerebral contamination. Brain Res 107:333–343, 1976.

    PubMed  CAS  Google Scholar 

  50. Hertz MM, Paulson OB: Heterogeneity of cerebral capillary flow in man and its consequences for estimation of blood-brain barrier permeability. J Clin Invest 65:1145–1151, 1980.

    PubMed  CAS  Google Scholar 

  51. Hertz MM, Paulson OB: Transfer across human blood-brain barrier: Evidence for capillary recruitment and for paradox glucose permeability increase in hypocapnia. Microvasc Res 24:364–376, 1982.

    PubMed  CAS  Google Scholar 

  52. Huang SC, Carson RE, Hoffman EJ, et al: Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and 15O-water. J Cereb Blood Flow Metab 3:141–153, 1983.

    PubMed  CAS  Google Scholar 

  53. Iannotti F, Alfano B, Pozzilli C, et al: Quantitative assessment of blood-brain barrier permeability to 68Ga-EDTA by positron emission tomography in human brain tumors. Acta Neurol Scand, 72:104, 1985.

    Google Scholar 

  54. Irwin GH, Preskorn SH: A dual label radiotracer technique for the simultaneous measurement of cerebral blood flow and the single-transit cerebral extraction of diffusion limited compounds in rats. Brain Res 249:23–30, 1982.

    PubMed  CAS  Google Scholar 

  55. Jarden JD, Dhawan V, Poltorak A, et al: Positron emission tomographic measurement of blood–to-brain and blood–to-tumor transport of 82Rb: The effect of dexamethasone and whole brain radiation therapy. Ann Neurol 18:636–646, 1985.

    PubMed  CAS  Google Scholar 

  56. Johanson CE, Woodbury DM: Uptake of [14C]urea by the in vivo choroid plexus-cerebrospinal fluidbrain system: Identification of sites of molecular sieving. J Physiol 275:167–176, 1978.

    PubMed  CAS  Google Scholar 

  57. Johnson JA, Wilson TA: A model for capillary exchange. Am J Physiol 210:1299–1303, 1966.

    PubMed  CAS  Google Scholar 

  58. Juhler M, Blasberg RG, Fenstermacher JD, et al: A spatial analysis of the blood-brain barrier in experimental allergic encephalomyelitis. J Cereb Blood Flow Metab 5:545–553, 1985.

    PubMed  CAS  Google Scholar 

  59. Katzman R, Leiderman PH: Brain potassium exchange in normal adult and immature rats. Am J Physiol 175:263–270, 1953.

    PubMed  CAS  Google Scholar 

  60. Kessler RM, Goble JC, Bird JH, et al: Measurement of blood-brain barrier permeability with positron emission tomography and 68Ga-EDTA.J Cereb Blood Flow Metab 4:323–328, 1984.

    PubMed  CAS  Google Scholar 

  61. Knott GD: M Lab—A mathematical modeling tool. Comput Programs Biomed 10:271–280, 1976.

    Google Scholar 

  62. Lammertsma AA, Brooks DJ, Beaney RP, et al: In vivo measurement of regional cerebral hematocrit using positron emission tomography. J Cereb Blood Flow Metab 4:317–332, 1984.

    PubMed  CAS  Google Scholar 

  63. Lammertsma AA, Brooks DJ, Frackowiak RSJ, et al: A method to quantitate fractional extraction of rubidium-82 across blood-brain barrier using positron emission tomography. J Cereb Blood Flow Metab 4:523–534, 1984.

    PubMed  CAS  Google Scholar 

  64. Lassen NA: Regional cerebral blood flow in cerebrovascular disease by SPECT (single photon emission computed tomography). J Neuroradiol 10:181–184, 1983.

    PubMed  CAS  Google Scholar 

  65. Lassen NA, Trap-Jensen J, Alexander SC, et al: Blood–brain barrier studies in man using the doubleindicator method. Am J Physiol 220:1627–1633, 1971.

    PubMed  CAS  Google Scholar 

  66. Lear JL, Ackermann RF, Kameyama M, et al: Evaluation of [123I]isopropyliodoamphetamine as a tracer for cerebral blood flow using direct autoradiographic comparison. J Cereb Blood Flow Metab 2:179–185, 1982.

    PubMed  CAS  Google Scholar 

  67. Levin VA, Ausman JI: Relationship of peripheral venous hematocrit to brain hematocrit. J Appl Physiol 26:433–437,1969.

    PubMed  CAS  Google Scholar 

  68. Levin V, Patlak CS: A compartmental analysis of 24Na kinetics in rat cerebrum, sciatic nerve and cerebrospinal fluid. J Physiol 224:559–581, 1972.

    PubMed  CAS  Google Scholar 

  69. Mans AM, Biebuyck JF, Shelly K, et al: Regional blood-brain barrier permeability to amino acids after portacaval anastomosis. J Neurochem 38:705–717, 1982.

    PubMed  CAS  Google Scholar 

  70. Marcus ML, Heistad DD, Ehrhardt JC, et al: Total and regional cerebral blood flow measurement with 7-, 10-, 25-, and 50 µm microspheres. J Appl Physiol 40:501–507, 1976.

    PubMed  CAS  Google Scholar 

  71. Neuwelt EA, Rapoport SI: Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed Proc 43:214–219, 1984.

    PubMed  CAS  Google Scholar 

  72. Ohno K, Chiueh CC, Burns EM, et al: Cerebrovascular integrity in protein-deprived rats. Brain Res Bull 5:251–255,1980.

    PubMed  CAS  Google Scholar 

  73. Ohno K, Pettigrew KD, Rapoport SI: Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol 235:H299–H307, 1978.

    PubMed  CAS  Google Scholar 

  74. Ohno K, Pettigrew KD, Rapoport SI: Local cerebral blood flow in the conscious rat as measured with 14Cantipyrine, 14C-iodoantipyrine and 3H-nicotine. Stroke 10:62–67, 1979.

    PubMed  CAS  Google Scholar 

  75. Oldendorf WH: Measurement of brain uptake of radiolabeled substances using a tritiated water internal standard. Brain Res 24:372–376, 1970.

    PubMed  CAS  Google Scholar 

  76. Oldendorf WH: The blood-brain barrier. In Bito LZ, Davson H, Fenstermacher JD (eds): The Occular and Cerebrospinal Fluids. Academic, New York, 1977, pp. 177–190.

    Google Scholar 

  77. Oldendorf WH: Clearance of radiolabeled substances by brain after arterial injection using a diffusible internal standard. In Marks N, Rodnight R (eds): Research Methods in Neurochemistry, Vol. 5. Plenum, New York, 1981, pp. 91–112.

    Google Scholar 

  78. Oldendorf WH: Speculations on functions of the blood-brain barrier. Adv Physiol Sci 7:349–353, 1982.

    Google Scholar 

  79. Oldendorf WH, Braun LD: [3H]Tryptamine and 3H-water as diffusible internal standards for measuring brain extraction of radio-labeled substances following carotid injection. Brain Res 113:219–224, 1976.

    PubMed  CAS  Google Scholar 

  80. Pardridge WM: Brain metabolism: A perspective from the blood-brain barrier. Physiol Rev 63:1481–1535, 1983.

    PubMed  CAS  Google Scholar 

  81. Pardridge WM, Crane PD, Mietus LJ, et al: Kinetics of regional blood-brain barrier transport and brain phosphorylation of glucose and 2-deoxyglucose in the barbiturate-anesthetized rat. J Neurochem 38:560–568, 1982.

    PubMed  CAS  Google Scholar 

  82. Pardridge WM, Fierer G: Blood–brain barrier transport of butanol and water relative to N-isopropyl-p- iodoamphetamine as the internal reference. J Cereb Blood Flow Metab 5:275–281, 1985.

    PubMed  CAS  Google Scholar 

  83. Pardridge WM, Landaw EM, Miller LP, et al: Carotid artery injection technique: Bounds for bolus mixing by plasma and by brain. J Cereb Blood Flow Metab 5:576–583, 1985.

    PubMed  CAS  Google Scholar 

  84. Pardridge WM, Oldendorf WH: Transport of metabolic substrates through the blood-brain barrier. J Neurochem 28:5–12, 1977.

    PubMed  CAS  Google Scholar 

  85. Patlak CS, Blasberg RG: Graphical evaluation of blood–to-brain transfer constants from multiple-time uptake data: Generalizations. J Cereb Blood Flow Metab 5:584–590, 1985.

    PubMed  CAS  Google Scholar 

  86. Patlak CS, Blasberg RG, Fenstermacher JD: Graphic evaluation of blood–to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7, 1983.

    PubMed  CAS  Google Scholar 

  87. Patlak CS, Fenstermacher JD: Measurements of dog blood-brain transfer constants by ventriculocisternal perfusion. Am J Physiol 229:877–884, 1975.

    PubMed  CAS  Google Scholar 

  88. Patlak CS, Pettigrew KD: A method to obtain infusion schedules for prescribed blood concentration time courses. J Appl Physiol 40:458–463, 1976.

    PubMed  CAS  Google Scholar 

  89. Paulson OB, Hertz MM: The indicator dilution method: Assumptions and applications to brain uptake. In Lambrecht RM, Rescigno A (eds): Tracer Kinetics and Physiologic Modeling. Springer-Verlag, Berlin, 1983, pp. 429–444.

    Google Scholar 

  90. Perlmutter JS, Larson KB, Raichle ME, et al: Strategies for in vivo measurement of receptor binding using positron emission tomography. J Cereb Blood Flow Metab 6:154–169, 1986.

    PubMed  CAS  Google Scholar 

  91. Phelps ME, Barrio JR, Huang SC, et al: Measurement of cerebral proteIn synthesis In man with positron computerized tomography: Model, assumptions and preliminary results, In Greitz T, Ingvar DH, Widen L, (eds): The Metabolism of the Human Brain Studied with Positron Emission Tomography. Raven, New York, 1985, pp. 215–232.

    Google Scholar 

  92. Phelps ME, Huang SC, Hoffman EJ, et al: Tomographic measurement of cerebral blood volume with 11Clabeled carboxyhemoglobin. J Nucl Med 20:328–334, 1979.

    PubMed  CAS  Google Scholar 

  93. Powers WJ, Raichle ME: Positron emission tomography and its application to the study of cerebrovascular disease in man. Stroke 16:361–376, 1985.

    PubMed  CAS  Google Scholar 

  94. Raichle ME: Positron emission tomography. Ann Rev Neurosci 6:249–267, 1983.

    PubMed  CAS  Google Scholar 

  95. Raichle ME, Eichling JO, Grubb RL: Brain permeability of water. Arch Neurol 30:319–321, 1974.

    PubMed  CAS  Google Scholar 

  96. Raichle ME, Eichling JO, Straatmann MG, et al: Blood–brain barrier permeability of 11C-labeled alcohols and 15O-labeled water. Am J Physiol 230:543–552, 1976.

    PubMed  CAS  Google Scholar 

  97. Rapoport SI: Blood–brain barrier in Physiology and Medicine. Raven, New York, 1976, pp. 1–206.

    Google Scholar 

  98. Rapoport SI, Fitzhugh R, Pettigrew KD, et al: Drug entry into and distribution within brain and cerebrospinal fluid: [14C]urea pharmacokinetics. Am J Physiol 242:R339–R348, 1982.

    PubMed  CAS  Google Scholar 

  99. Rapoport SI, Fredericks WR, Ohno K, et al: Quantitative aspects of reversible osmotic opening of the blood-brain barrier. Am J Physiol 238:R421–R431, 1980.

    PubMed  CAS  Google Scholar 

  100. Rapoport SI, Ohno K, Pettigrew KD: Drug entry into the brain. Brain Res 172:354–359, 1979.

    PubMed  CAS  Google Scholar 

  101. Rapoport SI, Ohno K, Pettigrew KD: Blood–brain barrier permeability in senescent rats. J Gerontol 34:162–169, 1979.

    PubMed  CAS  Google Scholar 

  102. Reese TS, Karnovsky MJ: Fine structural localization of a blood brain barrier to exogenous peroxidase. J Cell Biol 34:207–217, 1967.

    PubMed  CAS  Google Scholar 

  103. Reivich M, Alavi A, Wolf A, et al: Glucose metabolic rate kinetic model parameter determination in humans: The lumped constant and rate constants for [18F]fluorodeoxyglucose and [11C]deoxyglucose. J Cereb Blood Flow Metab 5:170–192, 1985.

    Google Scholar 

  104. Reivich M, Kuhl D, Wolf A, et al: The [18F]fluorodeoxyglucose method for the measurment of local cerebral glucose utilization in man. Circ Res 44:127–137, 1979.

    PubMed  CAS  Google Scholar 

  105. Riggs DS: The Mathematical Approach to Physiological Problems. MIT Press, Cambridge, Massachusetts, 1963, pp. 120–167.

    Google Scholar 

  106. Sage JI, Van Uitert RL, Duffy TE: Simultaneous measurement of cerebral blood flow and unidirectional movement of substances across the blood-brain barrier: Theory, method, and application to leucine. J Neurochem 36:1731–1738, 1981.

    PubMed  CAS  Google Scholar 

  107. Sakai F, Nakazawa K, Tazaki Y, et al: Regional cerebral blood volume and hematocrit measured in normal human volunteers by single photon emission computed tomography. J Cereb Blood Flow Metab 5:207– 213, 1985.

    PubMed  CAS  Google Scholar 

  108. Sakurada O, Kennedy C, Jehle J, et al: Measurement of local cerebral blood flow with iodo[14C]antipyrine. Am J Physiol 234:H59–H66, 1978.

    PubMed  CAS  Google Scholar 

  109. Sarna GS, Bradbury MWB, Cavanagh J: Permeability of the blood-brain barrier after portocaval anastomosis in the rat. Brain Res 138:550–554, 1977.

    PubMed  CAS  Google Scholar 

  110. Schafer JA, Gjedde A, Plum F: Regional cerebral blood flow in rat using n-[14C]butanol. Neurology (NY) 26:394, 1977.

    Google Scholar 

  111. Sisson WB, Oldendorf WH: Brain distribution spaces of mannitol3-H, inulin-14C, and dextran-14C in the rat. Am J Physiol 221:214–217, 1971.

    PubMed  CAS  Google Scholar 

  112. Smith QR, Gnaedinger JM: Comparison of [14C]urea and [14C]sucrose as indicators of regional bloodbrain barrier permeability using quantitative autoradiography. Soc Neurosci Abstr, 12:1258, 1986.

    Google Scholar 

  113. Smith QR, Johanson CE, Woodbury DM: Uptake of 36C1 and 22Na by the brain-cerebrospinal fluid system: Comparison of the permeability of the blood-brain and blood–cerebrospinal fluid barriers. J Neurochem 37:117–124, 1981.

    PubMed  CAS  Google Scholar 

  114. Smith QR, Rapoport SI: Carrier-mediated transport of chloride across the blood-brain barrier. J Neurochem 42:754–763, 1984.

    PubMed  CAS  Google Scholar 

  115. Smith QR, Rapoport SI: Cerebrovascular permeability coefficients to sodium, potassium and chloride. J Neurochem 46:1732–1742, 1986.

    PubMed  CAS  Google Scholar 

  116. Smith QR, Takasato Y. Kinetics of amino acid transport at the blood-brain barrier studied using an in situ brain perfusion technique. Ann NY Acad Sci, 481:186–201, 1986.

    PubMed  CAS  Google Scholar 

  117. Smith QR, Takasato Y, Rapoport SI: Kinetic analysis of L-leucine transport across the blood-brain barrier. Brain Res 311:167–170, 1984.

    PubMed  CAS  Google Scholar 

  118. Smith QR, Takasato Y, Sweeney DJ, et al: Regional cerebrovascular leucine transport as measured by the in situ brainperfusion technique. J Cereb Blood Flow Metab 5:300–311, 1985.

    PubMed  CAS  Google Scholar 

  119. Smith QR, Woodbury DM, Johanson CE: Kinetic analysis of [36C1]-, [22Na]- and [3H]mannitol uptake into the in vivo choroid plexus-cerebrospinal fluid-brain system: Ontogeny of the blood-brain and blood–CSF barriers. Dev Brain Res 3:181–198, 1982.

    CAS  Google Scholar 

  120. Sokoloff L: The radioactive deoxyglucose method: Theory, procedure, and applications for the measurement of local glucose utilization in the CNS. Adv Neurochem 4:46–59, 1982.

    Google Scholar 

  121. Solomon AK: Compartmental methods of kinetic analysis, In Comar CL, Bronner F (eds): Mineral Metabolism. Vol. 1. Academic, New York, 1960, pp. 119–167.

    Google Scholar 

  122. Takasato Y, Momma S, Smith QR: Kinetic analysis of cerebrovascular isoleucine transport from saline and plasma. J Neurochem 45:1013–1020, 1985.

    PubMed  CAS  Google Scholar 

  123. Takasato Y, Rapoport SI, Smith QR: An in situ brain perfusion technique to study cerebrovascular port in the rat. Am J Physiol 247:H484–H493, 1984.

    PubMed  CAS  Google Scholar 

  124. Taylor G: The dispersion of soluble matter in solvent flowing slowly through a tube. Proc R Soc Lond A 219:186–203, 1953.

    CAS  Google Scholar 

  125. Weiss HR, Buchweitz E, Murtha TJ, et al: Quantitative regional determination of morphometric indices of the total and perfused capillary network in the rat brain. Circ Res 51:494–503, 1982.

    PubMed  CAS  Google Scholar 

  126. Welch K: The principles of physiology of the cerebrospinal fluid in relation to hydrocephalus including normal pressure hydrocephalus. In Friedlander WJ (ed): Advances in Neurology. North-Holland, Amsterdam, 1975, pp. 247–332.

    Google Scholar 

  127. Wong DF, Gjedde A, Wagner HN: Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metab 6:137–146, 1986.

    PubMed  CAS  Google Scholar 

  128. Woods HF, Youdim MBH. The isolated perfused rat brain preparation—A critical assesment. Essays Neurochem 3:49–69, 1978.

    Google Scholar 

  129. Wright EM: Transport processes in the formation of the cerebrospinal fluid. Rev Physiol Biochem Pharmacol 83:1–34, 1978.

    CAS  Google Scholar 

  130. Yen CK, Budinger TF, Friedland RP, et al: Brain tumor evaluation using Rb-82 and positron emission tomography. J Nucl Med 23:532–537, 1982.

    PubMed  CAS  Google Scholar 

  131. Yudilevich DL, DeRose N: Blood–brain transfer of glucose and other molecules measured by rapid indicator dilution. Am J Physiol 220:841–846, 1971.

    PubMed  CAS  Google Scholar 

  132. Zivin JA, Snarr JF: A stable preparation for rat brain-perfusion: Effect of flow rate on glucose uptake. J Appl Physiol 32:658–663, 1972.

    PubMed  CAS  Google Scholar 

  133. Zlokovic BV, Begley DJ, Djuricic YY, et al: Measurement of solute transport across the blood-brain barrier in the perfused Guinea pig brain: Method and application to N-methyl-α-aminoisobutyric acid. J Neurochem 46:1444–1451, 1986.

    PubMed  CAS  Google Scholar 

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  1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Quentin R. Smith

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  1. The Oregon Health Sciences University School of Medicine, Portland, Oregon, USA

    Edward A. Neuwelt M.D.

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© 1989 Plenum Publishing Corporation

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Smith, Q.R. (1989). Quantitation of Blood-Brain Barrier Permeability. In: Neuwelt, E.A. (eds) Implications of the Blood-Brain Barrier and Its Manipulation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0701-3_4

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  • DOI: https://doi.org/10.1007/978-1-4613-0701-3_4

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