Hypoxia and Reoxygenation of a Cellular Barrier Consisting of Brain Capillary Endothelial Cells and Astrocytes

Pharmacological Interventions
  • H. Giese
  • K. Mertsch
  • R. F. Haselof
  • F. H. Härtel
  • I. E. Blasig
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)

Summary

Blood-brain barrier (BBB) has been neglected in pharmacological interventions of ischemic brain although it can be reached easily after systemic administration of a drug. Brain capillary endothelial cells (BCEC) may contain NMDA receptors so that the antagonist MK-80I was studied to protect BBB function. Oxygen deficiency is a main limitation during ischemia known to generate free radicals. During hypoxia and reoxygenation, an increase of radical-induced lipid peroxidation in both BCEC and astrocytes (AC) was found, accompanied by disturbances of BBB function. Therefore, the radical scavenging lazaroid U83836E was also studied. Upon hypoxia, the permeability of the barrier (BCEC and AC, cultured separately on the two sides of a filter) increased. This effect was intensified during the following reoxygenation. MK-801 and U83836E reduced the hypoxia-induced increase of permeability.

Keywords

NMDA Receptor Thiobarbituric Acid Reactive Substance Glutamate Uptake Glutathione Disulfide 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.

Résumé

La barrière hémato-encéphalique (BBB) a été négligée dans des interventions phar­macologiques du cerveau ischémique bien qu’il ne soit pas difficile de le démontrer après application d’un médicament. Des cellules endothéliales de cerveau (BCEC) possèdent des récepteurs NMDA de sorte que l’antagoniste MK-801 a été appliqué pour protéger la fonction de la barrière hémato-encéphalique. Un manque d’oxygène est la limitation essentielle pendant l’ischémie en produisant des radicaux libres. Pendant l’hypoxie et la reoxygenation une augmentation des taux de la péroxidation des lipides induite par des radicaux dans des BCEC et des astrocytes (AC) a été trouvée,ainsi que des modifications de la fonction de la BBB. De plus, l’aminostéroide U83836E, qui est un agent de spin-trap a été étudié. Sous hypoxie la perméabilité de la barrière formée de BCEC et de AC cultivés séparément sur les deux cotés d’un filtre a été augmentée, et le phénomène s’est intensifié après la réoxygena­tion.suivante. MK-801 et U83836E ont réduit le taux d’accroissement de la perméabilité provoqué par l’hypoxie.

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References

  1. 1.
    S.M. Rothman, and J.W. Olney, Glutamate and the pathophysiology of hypoxie-ischemic brain damage, Ann. Neurol., 19: 105 - 111 (1986).PubMedCrossRefGoogle Scholar
  2. 2.
    A. Volterra, D. Trotti, and G. Racagni, Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechnisms, Molec. Pharmacol., 46: 986 - 992 (1994).Google Scholar
  3. 3.
    S. Rehncrona, E. Westerberg, B. Akesson, and B.K. Siesjo, Brain cortical fatty acids during and following complete and severe incomplete ischemia, J. Neurochem., 38: 84 - 93 (1982).PubMedCrossRefGoogle Scholar
  4. 4.
    W. Cao, J.M. Carney, A. Duchon, R.A. Floyd, and M. Cheviot), Oxygen free radical involvment in ischemia and reperfusion injury to brain, Neurosc. Lett., 88: 233 - 238 (1988).CrossRefGoogle Scholar
  5. 5.
    L.L. Rubin, D.E. Hall, S. Porter. K. Barbu, C. Cannon, H.C. Horner, M. Janatpour, C.W. Liaw, K. Manning, J. Morales, L.L. Tanner, J. Tomaselli., and F. Bard, A cell culture model of the blood-brain barrier, J. Cell Biol., 115: 1725 - 1735 (1991).PubMedCrossRefGoogle Scholar
  6. 6.
    R.C. Janzer, and M.C. Raff, Astrocytes induce blood-brain barrier properties in endothelial cells, Nature (London), 325: 235 - 257 (1987).Google Scholar
  7. 7.
    P.M. Beart, K.-A.M. Sheehan, and D.T. Manallack, Absence of N-methyl-D-aspartate receptors on ovine cerebral microvessels, J. Cereb. Blood Flow. Metab., 8: 879 - 882 (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    H. Koenig, J.J. Trout, A.D. Goldstone, and Ch.Y. Lu, Capillary NMDA receptors regulate blood-brain barrier function and breakdown, Brain Res., 588: 297 - 303 (1992).PubMedCrossRefGoogle Scholar
  9. 9.
    T. Müller, J. Grosche, C. Ohlemeyer, and H. Kettenmann, NMDA-activated currents in Bergmann glial cells, Neuroreport, 4: 671 - 674 (1993).PubMedCrossRefGoogle Scholar
  10. 10.
    J.M. Luque, and J.G. Richards, Expression of NMDA 2B receptor subunit mRNA in Bergmann glia, Glia, 13: 228 - 232 (1995).PubMedCrossRefGoogle Scholar
  11. 11.
    A.-M. Lopez-Colome, A. Ortega, and M. Romo-de-Vivar, Excitatory amino acid-induced phosphoinositide hydrolysis in Müller glia, Glia, 9: 127 - 135 (1993).PubMedCrossRefGoogle Scholar
  12. 12.
    I. Sommer. C. Langenaur, and M. Schachner, Recognition of Bergmann glial and ependymal cells in the mouse nervous system by monoclonal antibody, J. Cell Biol., 90:448-458 (I 981).Google Scholar
  13. 13.
    L.A. McNaughton, and S.P. Hunt, Regulation of gene expression in astrocytes by excitatory amino acids. Brain Res. Mol. Brain Res., 16: 261 - 266 (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    D.J. Wyllie, and S.G. Cull-Candy, A comparison of NMDA receptor channels in type-2 astrocytes and granule cells from rat cerebellum, J. Physiol. (London), 475: 95 - 114 (1994).Google Scholar
  15. 15.
    A.J. Patel, A. Hunt. R.D. Gordon, and R. Balazs, The activities of different neural cell types of certain enzymes associated with the metabolic compartmentation of glutamate, Dev. Brain Res., 4: 3 - 11 (1982).CrossRefGoogle Scholar
  16. 16.
    A.M. Benjamin, Ammonia in metabolic interactions between neurons and glial, in glutamine, glutamate, and GABA in the central nervous system, (Hertz L., Kvamme E., McGeer, E.G., and Schousbe A., eds), pp. 399-414. Alan R. Liss, New York, (1983).Google Scholar
  17. 17.
    F.A. Tansey, M. Farooq, and W. Cammer, Glutamine synthetase in oligodendrocytes and astrocytes: New biochemical and immunocytochemical evidence, J. Neurochem., 56: 266 - 272 (1991).PubMedCrossRefGoogle Scholar
  18. 18.
    F.S. Silverstein, K. Buchanan, and M.V. Johnston, Perinatal hypoxia-ischemia disrupts striatal high affinity [3H] glutamate uptake into synaptosomes, J. Neurochem., 47: 1514 - 1619 (1986).CrossRefGoogle Scholar
  19. 19.
    S. Saweda, M. Higashima, and C. Yamamoto. Inhibition of high affinity uptake augment depolarizations of hippocampal neurons induced by glutamate, kainate, and related compounds, Exp. Brain Res., 60: 323 - 329 (1985).Google Scholar
  20. 20.
    G.J. McBean, and P.J. Roberts, Neurotoxicity of L-glutamate and D,L-threo-3-hydroxyaspartate in the rat striatum, J. Neurochem., 44: 247 - 254 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    E.H.F. Wong, J.A. Kemp, T. Priestley, A.R. Knight, G.N. Woodruff, and L.L. Iversen, The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist, Proc. Natl. Acad. Sci. USA, 83: 7104 - 7108 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    G. Sutherland, N. Haas, and J. Peeling, Ischemic neocortical protection with Ú74006F dose-response curve, Neurosci. Lett., 149: 123 - 125 (1986).CrossRefGoogle Scholar
  23. 23.
    H. Giese, K. Mcrtsch, and I.E. Blasig, Effect of MK-801 and U83836E on a porcine brain capillary endothelial cell barier during hypoxia, Neurosci. Lett., 191: 169 - 172 (1995).PubMedCrossRefGoogle Scholar
  24. 24.
    K. Mertsch, T. Crune, A. Ladhoff, and I.E. Blasig, Hypoxia and reoxygenation of brain endothelial cells in vitro: comparison of biochemical and morphological response, Cell. Mol. Biol., 41: 243 - 253 (1995).PubMedGoogle Scholar
  25. 25.
    J.B.M.M. Van Bree, A.G. De Boer. M. Danhof, L.A. Ginsel, and D.D. Breimer, Characterization of an “in vitro” blood-brain harrier: effects of molecular size and lipophilicity on cerebrovascular endothelial transport rates of drugs. J. Pharmacol. Exp. Ther., 247: 1233 - 1239 (1988).PubMedGoogle Scholar
  26. 26.
    J. Oehlke, S. Savoly, and I.E. Blasig, Utilization of endothelial cell monolayers of low tightness for estimation of transcellular transport characteristics of hydrophilic compounds, Eur. J. Pharmac. Sci., 2: 365 - 372 (1994).CrossRefGoogle Scholar
  27. 27.
    O.W. Griffith, Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine, Anal. Biochem., 106: 207 - 212 (1980).PubMedCrossRefGoogle Scholar
  28. 28.
    R.F. Haseloff, I.E. Blasig, H. Meffert, and B. Ebert, Hydroxyl radical scavenging and antipsoriatric activity of benzoic acid derivatives, Free Rad. Biol. Med., 9: 111 - 115 (1990).PubMedCrossRefGoogle Scholar
  29. 29.
    M.-P. Dehouck, St. Meresse, P. Delorme, J.C. Fruchart, and R. Cecchelli, An easier, reproducible, and mass-production method to study the blood-brain barrier in vitro. J. Neurochem., 54: 1798 - 1801 (1990).PubMedCrossRefGoogle Scholar
  30. 30.
    U. Jaehde, R. Masereeuw, A.G. De Boer, G. Fricker, J.F. Nagelkerke, J. Vonderscher, and D.D. Breimer, Quantification and visualization of the transport ofoctreotide, a somatostatin analogue, across monolayers of cerebrovascular endothelial cells, Pharmaceut. Res., 11: 442 - 448 (1994).CrossRefGoogle Scholar
  31. 31.
    K. Ohno, K.D. Pettigrew, and S.I. Rapoport, Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat, Am. J. Physiol., 235:11299-11307 (1978).Google Scholar
  32. 32.
    W.M. Pardridge, D. Triguero, J. Yang, and P.A. Cancilla, Comparison of in vitro and in vivo models of drug transcytosis through the blood-brain barrier, J. Pharmacol. Exp. Then, 253: 884 - 891 (1990).Google Scholar
  33. 33.
    K.L. Audus, F.L. Guillot, and J.M. Braughler, Evidence for 21 aminosteroid association with the hydrophobic domains of brain microvessel endothelial cells, Free Rad. Biol. Med., 11: 361 - 371 (1991).PubMedCrossRefGoogle Scholar
  34. 34.
    J.T. Greenamyre, J.M.M. Olson, J.B. (Jr) Penney, and A.B. Young. Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate-, and kainate-sensitive glutamate binding sites, J. Pharmacol. Exp. Ther., 233. 254 - 263 (1985).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • H. Giese
    • 1
  • K. Mertsch
    • 1
  • R. F. Haselof
    • 1
  • F. H. Härtel
    • 2
  • I. E. Blasig
    • 1
  1. 1.Forschungsinstitut für Molekulare PharmakologieBerlinGermany
  2. 2.Institut für Biologie Humboldt-Universität zu BerlinBerlinGermany

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