Abstract
The endothelial barrier between the blood and interstitial or extracellular fluid of the central nervous system (CNS) closely regulates the composition of the immediate extracellular environment of brain cells. This regulation ensures that the ionic composition of the CNS interstitial fluid, so vital to the normal functioning of brain cells, remains stable in the face of fluctuations in the blood circulating through brain and cord (Bradbury 1979). The means by which the regulation is brought about is the endothelium’s restriction in the movement of solutes between blood and its selective transfer of certain solutes. When a bolus of the glycoprotein horseradish peroxidase (HRP, ~40 kDa) is infused into the systemic blood, the HRP is excluded from the brain’s interstitial fluid by a continuous belt of tight junctions between adjacent endothelial cells and by the paucity of endocytotic pits and vesicles (Reese and Karnovsky 1967). The junctions, being zonular, seal the intercellular cleft, thereby preventing movement of solutes from blood into CNS extracellular fluid and from interstitial fluid into blood (Bodenheimer and Brightman 1968). Smaller hydrophilic molecules such as heme-peptide, about 2 kDa in size, are also excluded from brain by the same mechanism (Brightman et al. 1970). The passive flooding of the interstitium with serum that would occur were the junctions patent is prevented by the junctional belts which thereby enable the endothelium to act on a solute. The endothelium can then selectively regulate a solute’s passage by, e.g., metabolizing it or by endocytosing it after it binds to its receptor on the luminal face of the endothelium.
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References
Baker H, Spencer RF (1984) Olfactory receptor neurons are a peripheral conduit for access of foreign substances to the central nervous system. Soc Neurosci Abstr 10: 859
Baker H, Spencer RF (1986) Transneuronal transport of peroxidase-conjugated wheat germ agglutinin ( WGA-HRP) from the olfactory epithelium to the brain of adult rat. Exp Brain Res 63: 461–473
Bodenheimer TS, Brightman MW (1968) A blood-brain barrier to peroxidase in capillaries surrounded by perivascular spaces. Am J Anat 122: 249–267
Bradbury MWB (1979) The concept of the blood-brain barrier. Wiley, New York
Brightman MW (1968) The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. Prog Brain Res 29: 19–37
Brightman MW, Reese TS (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40: 648–677
Brightman MW, Reese TS, Feder N (1970) Assessment with the electronmicroscope of the permeability to peroxidase of cerebral endothelium and epithelium in mice and sharks. In: Crone C, Lassen NA (eds) Capillary permeability. Munksgaard, Copenhagen, pp 468–476
Brightman MW, Hori M, Rapoport SI, Reese TS, Westergard E (1973) Osmotic opening of tight junctions in cerebra; endothelium. J Comp Neurol 152: 317–326
Broadwell RB, Brightman MW (1976) Entry of peroxidase into neurons of the central and peripheral nervous system from extracerebral and cerebral blood. J Comp Neurol 166: 257–284
Broadwell RB, Brightman MW (1979) Cytochemistry of undamaged neurons transporting exogenous protein in vivo. J Comp Neurol 185: 31–74
Broadwell RB, Balin BJ (1985) Olfactory labeling from mucosa. Endocytotic and exocytotic pathways of the neuronal secretory process in transynaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo. J Comp Neurol 242: 632–650
Broadwell RB, Sofroniew MV (1993) Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol 120: 245–263
Card JP, Whealy ME, Robbins AK, Moore RY, Enquist LW (1991) Two a-herpes virus strains are transported differentially in the rodent visual system. Neuron 6: 957–969
Card JP, Rinaman L, Lynn RB, Lee B-H, Meade RP, Miselis RR, Enquist LW (1993) Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport and pathogenesis. J Neurosci 13: 2515–2539
Coulon P, Derbin C, Kucera P, Lafay F, Prehaud C, Flamand A (1989) Invasion of the peripheral nervous systems of adult mice by the CVS strain of rabies and its avirulent derivative Av01. J Virol 63: 3550–3554
Cunningham ET, DeSouza EB (1993) Interleukin 1 receptors in the brain and endocrine tissues. Immunol Today 14: 171–176
Da Cunha A, Jefferson JA, Jackson RW, Vitkovic L (1993) Glial cell-specific mechanisms of TGF-b1 induction by IL-1 in cerebral cortex. J Neuroimmunol 42: 71–86
Faustmann PM, Dermietzel R (1985) Extravasation of polymorophonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by alpha-bungarotoxin. Cell Tissue Res 242: 399–407
Field HJ, Hill TJ (1975) The pathogenesis of pseudorabies in mice: virus replication at the inoculation site and axonal uptake. J Gen Virol 26: 145–148
Flamand A, Gagner J-P, Morrison LA, Fields BN (1991) Penetration of the nervous systems of suckling mice by mammalian reoviruses. J Virol 65: 123–131
Harling-Berg C, Knopf PM, Merriam J, Cserr HF (1989) Role of cervical lymph nodes in the systemic humoral response to human serum albumin microinfused into rat cerebrospinal fluid. J Neuroimmunol 25: 185–193
Hickey WF (1991) T-lymphocyte entry and antigen recognition of the central nervous system. In: Ader R, Felten DL, Cohen N (eds) Psychoneuroimmunology, 2nd edn. Academic, New York, pp 149–175
Hickey WF, Kimura H (1988) Perivascular microglial cells of the CNS are bone marrow derived and present antigen in vivo. Science 239: 290–292
Huang AJ, Furie MB, Nicholson SC, Fischsbarg J, Kiebovitch LS, Silverstein SC (1988) Effects of human neutrophil chemotaxis across human endothelial cell monolayers on the permeability of these monolayers to ions and macromolecules. J Cell Physiol 135: 355–366
Hoogebrugge PM, Suzuki K, Suzuki K, Poorthuis BJHM, Kobayashi T, Wagamaker G, vanBekkum DW (1988) Donor-derived cells in the central nervous system of twitcher mice after bone marrow transplantation. Science 239: 1035–1038
Ishihara S, Sawada M, Chang L, Kim J-M, Brightman MW (1993) Brain vessels near muscle autografts are sites for entry of isogeneic macrophages into brain. Exp Neurol 124: 219–230
Jeffries WA, Brandon MR, Hunt SV (1984) Transferrin receptor on endothelium of brain capillaries. Nature 312: 162–163
Kuypers HGJM, Ugolini G (1990) Viruses as transneuronal tracers. Trends Neurosci 1s3: 71–75
Lucinskas FW, Cybulski MI, Kiely J-M, Pekind CS, Davis VM, Gimbrone MA (1991) Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule. J Immunol 146: 1617–11625
Marchand CF, Schwab ME (1986) Binding, uptake and retrograde axonal transport of herpes virus suis in sympathetic neurons. Brain Res 383: 262–270
Marcial MA, Carlson SL, Madara JL (1984) Partitioning of paracellular conductance along the ileai cryptvillus axis: a hypothesis based on structural analysis with detailed consideration of tight junction structure-function relationships. J Membr Biol 80: 59–70
Marshall DW, Brey RL, Butzin CA, Lucey DR, Abbadessa M, Boswell RN (1991) Changes in a longitudinal study of 124 neurologically normal HIV-1 infected United States Airforce personnel. J Acquir Immuno Defic Syndr 4: 777–781
McArthur JC, Nance-Sporson TE, Griffin DE, Hoover D, Seines OA, Miller EN, Margolick JB, Cohen BA, Farzadegan H, Saah A (1992) The diagnostic utility of elevation in cerebrospinal fluid betamicroglobulin in HIV-1 dementia. Neurology 42: 1707–1712
Metlay JP, Pure E, Steinman R (1989) Control of the immune response at the level of antigen-presenting cells: a comparison of the function of dendritic cells and B lymphocytes. Adv Immunol 47: 45–116
Milks LC, Conyers GP, Cramer EB (1986) The effect of neutrophil migration on epithelial permeability. J Cell Biol 103: 2729–2738
Morrison LA, Fields BN (1991) Viral pathogenesis and central nervous system infection. Semin Neurosci (3): 83–91
Morrison LA, Sidman RL, Fields BN (1991) Direct spread of reovirus from the intestinal lumen to the central nervous system through vagal autonomic nerve fibers. Proc Natl Acad Sci USA 88: 3852–3856
Neuwelt EA, Pagel MA, Dix RD (1991) Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier. J Neurosurg 74: 475–479
Oppenheimer-Marks N, Ziff M (1988) Migration of lymphocytes through endothelial cell monolayers: augmentation by interferon-y. Cell Immunol 114: 307–323
Petito CK, Cash KS (1992) Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol 32: 658–666
PoberJS, Gimbrone MA, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer T (1986) Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor and immune interferon. J Immunol 137: 1893–1896
Power C, Kong P-A, Crawford TO, Wesselingh S, Glass JD, McArthur JC (1993) Cerebral white matter changes in acquired immunodeficiency syndrome dementia: alterations of the blood-brain barrier. Ann Neurol 34: 339–350
Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheid WM (1991) Recombinant interleukin-1 induces mioningitis and blood-brain barrier injury in the rat. J Clin Invest 87: 1360–1366
Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34: 207–217
Rhodes RH (1991) Evidence of serum-protein leakage across the blood-brain barrier in the acquired immunodeficiency syndrome. J Neuropathol Exp Neurol 50: 171–183
Rosenberg ZF, Fauci AS (1990) Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol Today 11: 176–180
Sedgwick JD, Dörries R (1991) The immune system response to viral infection of the CNS. Semin Neurosci 3: 93–100
Shipley MT (1985) Transport of molecules from nose to brain: transneuronal antérograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull 15: 129–142
Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 425–434
Tyler KL, Fields BN (1990) Pathogenesis of viral infection. In: Fields BN, Knipe DM, Chanock RM, Hirsch MS, Melnick JL, Monath TP, Roizman B (eds) Virology, 2nd edn. Raven, New York, pp 1911–1240
Tyler KL, McPhee DA (1987) Molecular and genetic aspects of the pathogenesis of viral infections of the central nervous system. CRC Crit Rev Neurobiol 3: 221–243
Tyor WR, Glass JD, Griffin JW, Becker PS, McArthur JC, Bezman L, Griffin D (1992) Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann Neurol 31: 349–360
Vitkovic L, da Cunha A, Tyor WR (1994) Cytokine expression and pathogenesis in AIDS brain In: Price RW, Perry SW (eds) HIV, AIDS and the brain. Raven, New York, pp 203–222
Wahl S, Hunt DA, Wakefield LM, Francis NM, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor typeß induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84: 5788–5792
Weindl A (1973) Neuroendocrine aspects of circumventricular organs. In: Ganong WF, Martini L (eds) Frontiers in neuroendocrinology. Oxford University Press, London, pp 1–32
Ziegler RJ, Pozos RS (1981) Effects of lectins on peripheral infection by herpes simplex virus of rat sensory neurons in culture. Infect Immunol 34: 588–595
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Brightman, M.W., Ishihara, S., Chang, L. (1995). Penetration of Solutes, Viruses, and Cells Across the Blood-Brain Barrier. In: Oldstone, M.B.A., Vitković, L. (eds) HIV and Dementia. Current Topics in Microbiology and Immunology, vol 202. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79657-9_5
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