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

Pharmacological Interventions

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Biology and Physiology of the Blood-Brain Barrier

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 46))

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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.

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. S.M. Rothman, and J.W. Olney, Glutamate and the pathophysiology of hypoxie-ischemic brain damage, Ann. Neurol., 19: 105 - 111 (1986).

    Article  PubMed  CAS  Google Scholar 

  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).

    CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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. 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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  9. T. Müller, J. Grosche, C. Ohlemeyer, and H. Kettenmann, NMDA-activated currents in Bergmann glial cells, Neuroreport, 4: 671 - 674 (1993).

    Article  PubMed  Google Scholar 

  10. J.M. Luque, and J.G. Richards, Expression of NMDA 2B receptor subunit mRNA in Bergmann glia, Glia, 13: 228 - 232 (1995).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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. 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).

    Article  PubMed  CAS  Google Scholar 

  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).

    CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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. 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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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. 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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  22. G. Sutherland, N. Haas, and J. Peeling, Ischemic neocortical protection with Ú74006F dose-response curve, Neurosci. Lett., 149: 123 - 125 (1986).

    Article  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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).

    PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  27. O.W. Griffith, Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine, Anal. Biochem., 106: 207 - 212 (1980).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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. 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).

    CAS  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

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Giese, H., Mertsch, K., Haselof, R.F., Härtel, F.H., Blasig, I.E. (1996). Hypoxia and Reoxygenation of a Cellular Barrier Consisting of Brain Capillary Endothelial Cells and Astrocytes. In: Couraud, PO., Scherman, D. (eds) Biology and Physiology of the Blood-Brain Barrier. Advances in Behavioral Biology, vol 46. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9489-2_51

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  • DOI: https://doi.org/10.1007/978-1-4757-9489-2_51

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9491-5

  • Online ISBN: 978-1-4757-9489-2

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