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Blood-Brain Barrier Sodium Transport and Brain Edema Formation

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New Concepts of a Blood—Brain Barrier

Abstract

In most forms of brain edema, increased brain water results from a net increase in brain sodium and chloride contents (Betz et al., 1989). In vasogenic edema, the blood-brain barrier (BBB) is disrupted and sodium and chloride enter brain in a relatively unimpeded fashion. However, in cytotoxic edema, sodium and chloride must traverse an intact BBB. Thus, identification of the processes which mediate sodium and chloride transport across the brain capillary endothelial cells could lead to new therapy for cytotoxic brain edema through inhibition of BBB ion transport.

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References

  • Abbott N. J., Butt A. M., and Wallis W., 1986, The Na-K ATPase of the blood-brain barrier: a microelectrode study, Ann New York Acad Sci 481:390–391.

    Article  Google Scholar 

  • Betz A. L., 1983, Sodium transport from blood to brain: inhibition by furosemide and amiloride, J Neurochem 41:1158–1164.

    Article  PubMed  CAS  Google Scholar 

  • Betz A. L., 1985, Epithelial properties of brain capillary endothelium, Fed Proc 44:2614–2615.

    PubMed  CAS  Google Scholar 

  • Betz A. L. and Coester H. C., 1990, Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats, Stroke 21:1199–1204.

    Article  PubMed  CAS  Google Scholar 

  • Betz A. L., Ennis S. R., and Schielke G. P., 1989, Blood-brain barrier sodium transport limits development of brain edema during partial ischemia in gerbils, Stroke 20:1253–1259.

    Article  PubMed  CAS  Google Scholar 

  • Betz A. L., Firth J. A., and Goldstein G. W., 1980, Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells, Brain Res 192:17–28.

    Article  PubMed  CAS  Google Scholar 

  • Betz A. L., Iannotti F., and Hoff J. T., 1989, Brain edema: a classification based on blood-brain barrier integrity, Cerebrovasc Brain Metab Rev 1:133–154.

    PubMed  CAS  Google Scholar 

  • Betz A. L., Keep R. F., Beer M. E., and Ren X.-d., 1994, Blood-brain barrier permeability and brain content of sodium, potassium and chloride during focal ischemia, J Cereb Blood Flow Metab 14:29–37.

    Article  PubMed  CAS  Google Scholar 

  • Bradbury M. W. B. and Stulcová B., 1970, Efflux mechanism contributing to the stability of the potassium concentration in cerebrospinal fluid, J Physiol (Lond.) 208:415–430.

    CAS  Google Scholar 

  • Brust P., Baethmann A., Gjedde A., and Ermisch A., 1991, Atrial natriuretic peptide augments the blood-brain transfer of water but not leucine and glucose, Brain Res 564:91–96.

    Article  PubMed  CAS  Google Scholar 

  • Butt A. M. and Jones H. C, 1992, Effect of histamine and antagonists on electrical resistance across the blood-brain barrier in rat brain-surface microvessels, Brain Res 569:100–105.

    Article  PubMed  CAS  Google Scholar 

  • Chaplin E. R., Free R. G., and Goldstein G. W., 1981, Inhibition by steroids of the uptake of potassium by capillaries isolated from rat brain, Biochem Pharmacol 30:241–245.

    Article  PubMed  CAS  Google Scholar 

  • Crone C., 1986, The blood-brain barrier as a tight epithelium: where is information lacking?, Ann New York Acad Sci 481:174–185.

    Article  CAS  Google Scholar 

  • Davson H., 1955, A comparative study of the aqueous humour and cerebrospinal fluid in the rabbit, J Physiol 129:111–133.

    PubMed  CAS  Google Scholar 

  • Davson H. and Segal M. B., 1970, The effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid and the brain, J Physiol 209:131–153.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • DePasquale M, Patlak C. S., and Cserr H. F., 1989, Brain ion and volume regulation during acute hypernatremia in Brattleboro rats, Am J Physiol 256: F1059–F1066.

    PubMed  CAS  Google Scholar 

  • Dickinson L. D. and Betz A. L., 1992, Attenuated development of ischemic brain edema in vasopressin-deficient rats, J Cereb Blood Flow Metab 12:681–690.

    Article  PubMed  CAS  Google Scholar 

  • Ennis S. R., Keep R. F., Schielke G. P., and Betz A. L., 1990, Decrease in perfusion of cerebral capillaries during incomplete ischemia and reperfusion, J Cereb Blood Flow Metab 10:213–220.

    Article  PubMed  CAS  Google Scholar 

  • Ermisch A., Riihle H. J., Kretzschmar R., and Baethmann A., 1991, On the blood-brain barrier to peptides: Specific binding of atrial natriuretic peptide in vivo and in vitro, Brain Res 554:209–216.

    Article  PubMed  CAS  Google Scholar 

  • Firth J. A., 1976, Cytochemical localization of the K+ regulation interface between blood and brain, Experientia 33:1093–1094.

    Article  Google Scholar 

  • Gadsby D. C, 1984, The Na/K pump of cardiac cells, Ann Rev Biophys Bioeng 13:373–398.

    Article  CAS  Google Scholar 

  • Goldstein G. W., 1979, Relation of potassium transport to oxidative metabolism in isolated brain capillaries, J Physiol 286:185–195.

    PubMed  CAS  Google Scholar 

  • Gotoh O., Asano T., Koide T., and Takakura K., 1985, Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125 I-albumin, Stroke 16:101–109.

    Article  PubMed  CAS  Google Scholar 

  • Hansen A. J. and Nedergaard M., 1988, Brain ion homeostasis in cerebral ischemia, Neurochem Path 9:195–209.

    CAS  Google Scholar 

  • Harik S. I., 1986, Blood-brain barrier sodium/potassium pump: modulation by central noradrenergic innervation, Proc Natl Acad Sci USA 83:4067–4070.

    Article  PubMed  CAS  Google Scholar 

  • Harik S. I., Sharma V. K., Wetherbee J. R., Warren R. H., and Banerjee S. P., 1981, Adrenergic and cholinergic receptors of cerebral microvessels, J Cereb Blood Flow Metab 1:329–338.

    Article  PubMed  CAS  Google Scholar 

  • Herbst T. J., Raichle M. E., and Ferrendelli J. A., 1979, β-Adrenergic regulation of adenosine 3′,5′-monophosphate concentration in brain microvessels, Science 204:330–332.

    Article  PubMed  CAS  Google Scholar 

  • Hoyer J., Popp R., Meyer J., Galla H.-J., and Gögelein H., 1991, Angiotensin II, vasopressin and GTP[Îł-S] inhibit inward-rectifying K+ channels in porcine cerebral capillary endothelial cells, J Membrane Biol 123:55–62.

    Article  CAS  Google Scholar 

  • Ibaragi M.-A., Niwa M., and Ozaki M., 1989, Atrial natriuretic peptide modulates amiloride-sensitive Na+ transport across the blood-brain barrier, J Neurochem 53:1802–1806.

    Article  PubMed  CAS  Google Scholar 

  • Ishimaru S., Okada Y., Mies G., and Hossmann K.-A., 1993, Relationship between blood flow and blood-brain barrier permeability of sodium and albumin in focal ischaemia of rats: a triple tracer autoradiographic study, Acta Neurochir (Wien) 120:72–80.

    Article  CAS  Google Scholar 

  • Kalaria R. N., Stockmeier C. A., and Harik S. I., 1989, Brain microvessels are innervated by locus ceruleus noradrenergic neurons, Neurosci Lett 97:203–208.

    Article  PubMed  CAS  Google Scholar 

  • Kanda F., Sarnacki P., and Arieff A. I., 1992, Atrial natriuretic peptide inhibits amiloride-sensitive sodium uptake in rat brain, Am J Physiol Regul Integr Comp Physiol 263:R279–R283.

    CAS  Google Scholar 

  • Keep R. F., Xiang J., and Betz A. L., 1993, Potassium transport at the blood-brain and blood-CSF barriers, in: “Frontiers in Cerebrovascular Biology. Transport and its Regulation,” L. R. Drewes and A. L. Betz, eds., New York, Plenum, pp. 43–54.

    Google Scholar 

  • Longa E. Z., Weinstein P. R., Carlson S., and Cummins R., 1989, Reversible middle cerebral artery occlusion without craniectomy in rats, Stroke 20:84–91.

    Article  PubMed  CAS  Google Scholar 

  • McDonough A. A., Geering K., and Farley R. A., 1990, The sodium pump needs its β subunit, FASEB J 4:1598–1605.

    PubMed  CAS  Google Scholar 

  • Menzies S.A., Betz A. L., and Hoff J. T., 1993, Contributions of ions and albumin to the formation and resolution of ischemic brain edema, J Neurosurg 78:257–266.

    Article  PubMed  CAS  Google Scholar 

  • Milhorat T. H., Hammock M. K., and Fenstermacher J. D., 1971, Cerebrospinal fluid production by the choroid plexus and brain, Science 173:330–332.

    Article  PubMed  CAS  Google Scholar 

  • Murphy V. A. and Johanson C. E., 1989, Acidosis, acetazolamide, and amiloride: effects on 22Na transfer across the blood-brain and blood-CSF barriers, J Neurochem 52:1058–1063.

    Article  PubMed  CAS  Google Scholar 

  • Nag S., 1990, Ultracytochemical localisation of Na+, K+-ATPase in cerebral endothelium in acute hypertension, Acta Neuropathol(Berl) 80:7–11.

    Article  CAS  Google Scholar 

  • Nakao N., Itakura T., Hideyoshi Y., Nakai K., and Komai N., 1990, Effect of atrial natriuretic peptide on ischemic brain edema: changes in brain water and electrolytes, Neurosurg 27:39–44.

    Article  CAS  Google Scholar 

  • Oldendorf W. H., Cornford M. E., and Brown W. J., 1977, The large apparent work capacity of the blood-brain barrier: a study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat, Ann Neurol 1:409–417.

    Article  PubMed  CAS  Google Scholar 

  • Pearlmutter A. F., Szkrybala M., Kim Y., and Harik S. I., 1988, Arginine vasopressin receptors in pig cerebral microvessels, cerebral cortex and hippocampus, Neurosci Lett 87:121–126.

    Article  PubMed  CAS  Google Scholar 

  • Raichle M. E. and Grubb R. L. Jr., 1978, Regulation of brain water permeability by centrally-released vasopressin, Brain Res 143:191–194.

    Article  PubMed  CAS  Google Scholar 

  • Raichle M. E., Hartman B. K., Eichling J. O., and Sharpe L. G., 1975, Central noradrenergic regulation of cerebral blood flow and vascular permeability, Proc Nat Acad Sci USA 72:3726–3730.

    Article  PubMed  CAS  Google Scholar 

  • Rapoport S. I., 1976, “Blood-Brain Barrier in Physiology and Medicine,” Raven Press, New York.

    Google Scholar 

  • Rosenberg G. A., Kyner W. T., Fenstermacher J. D., and Patlak C. S., 1986, Effect of vasopressin on ependymal and capillary permeability to tritiated water in cat, Am J Physiol 251:F485–F489.

    PubMed  CAS  Google Scholar 

  • Schielke G. P. and Betz A. L., 1993, Electrolyte transport, in: “Physiology and Pharmacology of the Blood-Brain Barrier,” M. W. B. Bradbury, ed., Heidelberg, Springer-Verlag, pp. 221–244.

    Google Scholar 

  • Schielke G. P., Moises H. C., and Betz A. L., 1990, Potassium activation of the Na, K-pump in isolated brain microvessels and synaptosomes, Brain Res 524:291–296.

    Article  PubMed  CAS  Google Scholar 

  • Schielke G. P., Moises H. C., and Betz A. L., 1991, Blood to brain sodium transport and interstitial fluid potassium concentration during focal ischemia in the rat, J Cereb Blood Flow Metab 11:466–471.

    Article  PubMed  CAS  Google Scholar 

  • Spector R. and Johanson C. E., 1989, The mammalian choroid plexus, Sci Am 261:68–74.

    Article  PubMed  CAS  Google Scholar 

  • Steardo L. and Nathanson J. A., 1987, Brain barrier tissues: end organs for atriopeptins, Science 235:470–473.

    Article  PubMed  CAS  Google Scholar 

  • Sweadner K. J., 1989, Isozymes of the Na+/K+-ATPase, Biochim Biophys Acta 988:185–220.

    Article  PubMed  CAS  Google Scholar 

  • Szentistványi I., Patlak C. S., Ellis R. A., and Cserr H. F., 1984, Drainage of interstitial fluid from different regions of rat brain, Am J Physiol 246:F835–F844.

    PubMed  Google Scholar 

  • Vigne P., Champigny G., Marsault R., Barbry P., Frelin C., and Lazdunski M., 1989, A new type of amiloride-sensitive cationic channel in endothelial cells of brain microvessels, J Biol Chem 264:7663–7668.

    PubMed  CAS  Google Scholar 

  • Vorbrodt A. W., Lossinsky A. S., and Wisniewski H. M., 1982, Cytochemical localization of ouabain-sensitive, K+-dependent P-nitro-phenylphosphatase (transport ATPase) in the mouse central and peripheral nervous systems, Brain Res 243:225–234.

    Article  PubMed  CAS  Google Scholar 

  • Yang G. Y., Chen S. F., Kinouchi H., Chan P. H., and Weinstein P. R., 1992, Edema, cation content, and ATPase activity after middle cerebral artery occlusion in rats, Stroke 23:1331–1336.

    Article  PubMed  CAS  Google Scholar 

  • Young W., Rappaport Z. H., Chalif D. J., and Flamm E. S., 1987, Regional brain sodium, potassium, and water changes in the rat middle cerebral artery occlusion model of ischemia, Stroke 18:751–759.

    Article  PubMed  CAS  Google Scholar 

  • Zlokovic B. V., Mackic J. B., Wang L., McComb J. G., and McDonough A., 1993, Differential expression of Na, K-ATPase alpha and beta subunit isofonns at the blood-brain barrier and the choroid plexus, J Biol Chem 268:8019–8025.

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, MI, USA

    A. Lorris Betz, Steven R. Ennis, Xiao-dan Ren & Richard F. Keep

  2. Departments of Pediatrics, and Neurology, University of Michigan, Ann Arbor, MI, USA

    A. Lorris Betz

  3. Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI, USA

    Gerald P. Schielke

Authors
  1. A. Lorris Betz
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  2. Steven R. Ennis
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  3. Xiao-dan Ren
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  4. Gerald P. Schielke
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  5. Richard F. Keep
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Editor information

Editors and Affiliations

  1. Institute of Ophthalmology, University College London, London, England

    John Greenwood

  2. King’s College, University of London, London, England

    David J. Begley

  3. United Medical and Dental Schools, St. Thomas’ Hospital, London, England

    Malcolm B. Segal

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Betz, A.L., Ennis, S.R., Ren, Xd., Schielke, G.P., Keep, R.F. (1995). Blood-Brain Barrier Sodium Transport and Brain Edema Formation. In: Greenwood, J., Begley, D.J., Segal, M.B. (eds) New Concepts of a Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1054-7_16

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  • DOI: https://doi.org/10.1007/978-1-4899-1054-7_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-1056-1

  • Online ISBN: 978-1-4899-1054-7

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