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Some Aspects of the Pharmacology of Adrenal Steroids and the Central Nervous System

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Steroids and Brain Edema

Abstract

The pharmacology and biochemistry of adrenal steroids as they relate to the central nervous system (CNS) have been extensively reviewed by Woodbury [76, 77]. In order to reduce redundancy, the present review has been limited to aspects of steroid pharmacology pertinent to their use in the therapy of brain edema. First, the uptake, distribution, exit and metabolism of glucorticoids have been discussed in detail. Second, the effects of both glucocorticoids and mineralocorticoids on CNS electrolyte metabolism in normal and pathological states have been summarized.

Supported by a United States Public Health Service Program-Project Grant (5-PO1-NS-04553) from the National Institute of Neurological Diseases and Stroke, National Institutes of Health.

Recipient of a USPHS Research Career Program Award (5-K6-NS-13, 838) from the National Institute of Neurological Diseases and Stroke, National Institutes of Health.

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References

  1. Angel, C, Burkett, M. L.: Effects of hydrocortisone and cycloheximide on blood-brain barrier function in the rat. Dis. nerv. Syst. 32, 53–58 (1971).

    PubMed  CAS  Google Scholar 

  2. Axelrod, L. R.: The metabolism of corticosteroids by incubated and perfused brain tissues. In: Influence of Hormones on the Nervous System, pp. 74–84. Ford, D. H. (Ed.), Basel: S. Karger 1971.

    Google Scholar 

  3. Bakay, L., Lee, J. C: Cerebral Edema. Springfield, Illinois: Charles C. Thomas 1965.

    Google Scholar 

  4. Baron, D. N., Abelson, D.: Cortisone and hydrocortisone in cerebrospinal fluid. Nature 173, 174 (1954).

    Article  PubMed  CAS  Google Scholar 

  5. Benson, V. M., McLaurin, R. L., Foulkes, E. C: Traumatic cerebral edema. Arch. Neurol. 23, 179–186 (1970).

    PubMed  CAS  Google Scholar 

  6. Blinderman, E. E., Graf, C. J., Fitzpatrick, T.: Basic studies in cerebral edema. Its control by a corticosteroid (solu-medrol). J. Neurosurg. 19, 319–324 (1962).

    Article  PubMed  CAS  Google Scholar 

  7. Bottoms, G., Goetsch, D. D.: Subcellular distribution of the (8H) corticosterone fraction in brain, thymus, heart, and liver of the rat. Proc. Soc. exp. Biol. 124, 662–665 (1967).

    PubMed  CAS  Google Scholar 

  8. Brooks, S. M., Werk, E. E., Ackerman, S. J., Sullivan, I., Thrasher, K.: Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. New Engl. J. Med. 286, 1125–1128 (1972).

    Article  PubMed  CAS  Google Scholar 

  9. Buhrley, L. E., Reed, D. J.: The effect of furosemide on sodium-22 uptake into cerebrospinal fluid and brain. Exp. Brain Res. 14, 503–510 (1972).

    Article  PubMed  CAS  Google Scholar 

  10. Butte, J. C, Kakihana, R., Noble, E. P.: Rat and mouse brain corticosterone. Endocrinology 90, 1091–1100 (1972).

    Article  PubMed  CAS  Google Scholar 

  11. Clasen, R. A., Cooke, P. M., Pandolfi, S., Carnecki, G, Hass, G. M.: Steroid-antihistaminic therapy in experimental cerebral edema. Arch. Neurol. 13, 584–592 (1965).

    PubMed  CAS  Google Scholar 

  12. Colfer, H. F.: Studies on the relationship between electrolytes of the cerebral cortex and the mechanism of convulsions. Proc. Ass. Res. Nerv. Diseases 26, 98–117 (1947).

    CAS  Google Scholar 

  13. Coppen, A., Brooksbank, B. W. L., Noguera, R., Wilson, D. A.: Cortisol in the cerebrospinal fluid of patients suffering from affective disorders. J. Neurol. Neurosurg. Psychiat. 34, 432–435 (1971).

    Article  PubMed  CAS  Google Scholar 

  14. DeVenuto, F., Chader, G.: Interactions between Cortisol or corticosterone and fractions of rat thymus, brain and heart cell. Biochim. biophys. Acta (Amst.) 121, 151–158 (1966).

    CAS  Google Scholar 

  15. Domer, F. R.: Effects of diuretics on cerebrospinal fluid formation and potassium movement. Exp. Neurol. 24, 54–64 (1969).

    Article  PubMed  CAS  Google Scholar 

  16. Eik-Nes, K. B., Brizzee, K. R.: Concentration of tritium in brain tissue of dogs given [1,2-3H2] Cortisol intravenously. Biochim. biophys. Acta (Amst.) 97, 320–333 (1965).

    CAS  Google Scholar 

  17. Eisenberg, H. M., Barlow, C. F., Lorenzo, A. V.: Effect of dexamethasone on altered brain vascular permeability. Arch. Neurol. 23, 18–22 (1970).

    PubMed  CAS  Google Scholar 

  18. Fingl, E.: Absorption, distribution, and elimination: practical pharmacokinetics. In: Antiepileptic Drugs, pp. 7–21. Woodbury, D. M., Penry, J. K., Schmidt, R. P. (Eds), New York: Raven Press 1972.

    Google Scholar 

  19. Fishman, R. A., Christy, N. P.: Fate of adrenal cortical steroids following intrathecal injection. Neurology 15, 1–6 (1965).

    PubMed  CAS  Google Scholar 

  20. Ford, D. H., Rhines, R. K., Stieg, C.: Hormone localization in the nervous system. In: Influence of Hormones on the Nervous System, pp. 2–16. Ford, D. H. (Ed.), Basel: S. Karger 1971.

    Google Scholar 

  21. Fukuda, T., Ui, J.: Breakdown of blood-cerebrospinal fluid barrier for calcium ions in the absence of glucosteroids. Nature 214, 598–599 (1967).

    Article  CAS  Google Scholar 

  22. Gallagher, B. B., Glaser, G. H.: Seizure threshold, adrenalectomy and sodium-potassium stimulated ATPase in rat brain. J. Neurochem. 15, 525–528 (1968).

    Article  PubMed  CAS  Google Scholar 

  23. Gerlach, J. L., McEwen, B. S.: Rat brain binds adrenal steroid hormone: radioautography of hippocampus with corticosterone. Science 175, 1133–1136 (1972).

    Article  PubMed  CAS  Google Scholar 

  24. Grosser, B. I: 11β-hydroxysteroid metabolism by mouse brain and glioma 261. J. Neurochem. 13, 475–478 (1966).

    Article  PubMed  CAS  Google Scholar 

  25. Grosser, B. I., Axelrod, L. R.: Acetylation of Cortisol by neonatal rat brain in vitro. Steroids 9,229–234 (1967).

    Article  PubMed  CAS  Google Scholar 

  26. Grosser, B. I., Axelrod, L. R.: Conversion of Cortisol to Cortisol acetate, cortisone acetate and cortisone by the developing primate brain. Steroids 11, 827–836 (1968).

    Article  PubMed  CAS  Google Scholar 

  27. Grosser, B. I., Bliss, E. L.: Metabolism of 11-hydroxysteroids by cerebral tissues in vitro. Steroids 8,915–928 (1966).

    Article  PubMed  CAS  Google Scholar 

  28. Grosser, B. I., Krowas, S. T.: Acetylation of Cortisol by a human astrocytoma. J. clin. Endocr. 31,591 (1970).

    Article  Google Scholar 

  29. Grosser, B. I., Reed, D. J.: Uptake and metabolism of Cortisol and corticosterone by rat cerebral cortex in vivo. Exp. Neurol, (in press).

    Google Scholar 

  30. Grosser, B. I., Stevens, W., Bruenger, F. W., Reed, D. J.: Corticosterone binding by rat brain cytosol. J. Neurochem. 18, 1725–1732 (1971).

    Article  PubMed  CAS  Google Scholar 

  31. Haque, N., Thrasher, K., Werk, Jr., E. E., Knowles, Jr., H. C, Sholiton, L. J.: Studies on dexamethasone metabolism in man: effect of diphenylhydantoin. J. clin. Endocr. 34, 44–50 (1972).

    Article  PubMed  CAS  Google Scholar 

  32. Harris, A. B.: Steroids and blood-brain barrier alterations in sodium acetrizoate injury. Arch. Neurol. 17, 282–297 (1967).

    PubMed  CAS  Google Scholar 

  33. Henkin, R. I., Casper, A. G. T., Brown, R., Harlan, A. B., Bartter, F. C.: Presence of corticosterone and Cortisol in the central and peripheral nervous system of the cat. Endocrinology 82, 1058–1061 (1968).

    Article  PubMed  CAS  Google Scholar 

  34. Hoagland, H.: Studies of brain metabolism and electrical activity in relation to adrenocortical physiology. Recent Progr. Hormone Res. 10, 29–63 (1954).

    CAS  Google Scholar 

  35. Hooshmand, H., Dove, J., Houff, S., Suter, C.: Effects of diuretics and steroids on CSF pressure. Arch. Neurol. 21, 499–509 (1969).

    PubMed  CAS  Google Scholar 

  36. Johnson, J. A., Assam, S.: Use of betamethasone in reduction of cerebral edema. Milit. Med. 131, 44–47 (1966).

    CAS  Google Scholar 

  37. Katzman, R., Aleu, F., Wilson, C.: Further observations on triethyltin edema. Arch. Neurol. 9, 178–187 (1963).

    PubMed  CAS  Google Scholar 

  38. Klatzo, I.: Presidential address. Neuropathological aspects of brain edema. J. Neuropath, exp. Neurol. 26, 1–14 (1967).

    Article  CAS  Google Scholar 

  39. Long, D. M., Hartmann, J. F., French, L. A.: The response of experimental cerebral edema to glucosteroid administration. J. Neurosurg. 24, 842–854 (1966).

    Google Scholar 

  40. Mahesh, V. B., Ulrich, F.: Metabolism of Cortisol and cortisone by various tissues and subcellular particles. J. biol. Chem. 235, 356–360 (1960).

    PubMed  CAS  Google Scholar 

  41. Maxwell, R. E., Long, D. M., French, L. A.: The effects of glucosteroids on experimental cold-induced brain edema. J. Neurosurg. 34, 477–487 (1971).

    Article  PubMed  CAS  Google Scholar 

  42. McEwen, B. S., Magnus, C., Wallach, G.: Soluble corticosterone-binding macromolecules extracted from rat brain. Endocrinology 90, 217–226 (1972).

    Article  PubMed  CAS  Google Scholar 

  43. McEwen, B. S., Weiss, J. M., Schwartz, L. S.: Selective retention of corticosterone by limbic structures in rat brain. Nature 220, 911–912 (1968).

    Article  PubMed  CAS  Google Scholar 

  44. McEwen, B. S., Weiss, J. M., Schwartz, L. S.: Uptake of corticosterone by rat brain and its concentration by certain limbic structures. Brain Res. 16, 227–241 (1969).

    Article  PubMed  CAS  Google Scholar 

  45. McEwen, B. S., Weiss, J. M., Schwartz, L. S.: Retention of corticosterone by cell nuclei from brain regions of adrenalectomized rats. Brain Res. 17, 471–482 (1970).

    Article  PubMed  CAS  Google Scholar 

  46. Miner, L. C, Reed, D. J.: The effect of ethacrynic acid on sodium uptake into the cerebrospinal fluid of the rat. Arch. int. Pharmacodyn. 190, 316–321 (1971).

    PubMed  CAS  Google Scholar 

  47. Mitus, A.: Dexamethasone. Its effectiveness in the treatment of the acute symptoms of meningeal leukemia. Amer. J. Dis. Child. 117, 307–312 (1969).

    PubMed  CAS  Google Scholar 

  48. Murphy, B. E. P., Cosgrove, J. B., McIlquham, M. C, Pattee, C. J.: Adrenal corticoid levels in human cerebrospinal fluid. Canad. med. Ass. J. 97, 13–17 (1967).

    PubMed  CAS  Google Scholar 

  49. Nakazawa, S.: Biochemical studies of cerebral tissues in experimentally induced edema. Neurology 19, 269–276 (1969).

    PubMed  CAS  Google Scholar 

  50. O’Toole, R. D., Thornton, G. F., Mukherjee, M. K., Nath, R. L.: Dexamethasone in tuberculous meningitis. Relationship of cerebrospinal fluid effects to therapeutic efficacy. Ann. intern. Med. 70, 39–48 (1969).

    PubMed  Google Scholar 

  51. Overman, R. R., Davis, A. K., Bass, A. C: Effects of cortisone and DCA on radiosodium transport in normal and adrenalectomized dogs. Amer. J. Physiol. 167, 333–340 (1951).

    PubMed  CAS  Google Scholar 

  52. Pappius, H. M., Gulati, D. R.: Water and electrolyte content of cerebral tissues in experimentally induced edema. Acta neuropath. (Berl.) 2, 451–460 (1963).

    Article  CAS  Google Scholar 

  53. Pappius, H. M., McCann, W. P.: Effects of steroids on cerebral edema in cats. Arch. Neurol. 20, 207–216 (1969).

    PubMed  CAS  Google Scholar 

  54. Peterson, N. A., Chaikoff, I. L.: Uptake of intravenously-injected [4-14C] Cortisol by adult rat brain. J. Neurochem. 10, 17–23 (1963).

    Article  CAS  Google Scholar 

  55. Peterson, N. A., Chaikoff, I. L. Jones, C.: The in vitro conversion of Cortisol to cortisone by subcellular brain fractions of young and adult rats. J. Neurochem. 12, 273–278 (1965).

    Article  PubMed  CAS  Google Scholar 

  56. Reed, D. J.: The effects of acetazolamide on pentobarbital sleep-time and cerebrospinal fluid flow of rats. Arch. int. Pharmacodyn. 171, 206–215 (1968).

    PubMed  CAS  Google Scholar 

  57. Reed, D. J.: The effect of furosemide on cerebrospinal fluid flow in rabbits. Arch. int. Pharmacodyn. 178, 324–330 (1969).

    PubMed  CAS  Google Scholar 

  58. Reulen, H. J., Medzihradsky, F., Enzenbach, R., Marguth, F., Brendel W.: Electrolytes, fluids, and energy metabolism in human cerebral edema. Arch. Neurol. 21,517–525 (1969).

    PubMed  CAS  Google Scholar 

  59. Rovit, R. L., Hagan, R.: Steroids and cerebral edema: the effects of glucocorticoids on abnormal capillary permeability following cerebral injury in cats. J. Neuropath, exp. Neurol. 27, 277–299 (1968).

    Article  CAS  Google Scholar 

  60. Sato, K., Yamaguchi, M., Mullan, S., Evans, J. P., Ishii, S.: Brain edema. A study of biochemical and structural alterations. Arch. Neurol. 21, 413–424 (1969).

    PubMed  CAS  Google Scholar 

  61. Schwartz, M. L., Tator, C. H., Hoffman, H. J.: The uptake of hydrocortisone in mouse brain and ependymoblastoma. J. Neurosurg. 36, 178–183 (1972).

    Article  PubMed  CAS  Google Scholar 

  62. Shenkin, H. A., Gutterman, P.: The analysis of body water compartments in postoperative craniotomy patients. Part 3: The effects of dexamethasone. J. Neurosurg. 31, 400–407 (1969).

    Article  PubMed  CAS  Google Scholar 

  63. Sholiton, L. J., Werk, Jr., E. E., MacGee, J.: Metabolism of cortisol-4-C14 and cortisone-4-C14 by rat brain homogenates. Metabolism 14, 1122–1127 (1965).

    Article  PubMed  CAS  Google Scholar 

  64. Steiner, F. A., Ruf, K., Akert, K.: Steroid-sensitive neurones in rat brain: anatomical localization and responses to neurohumours and ACTH. Brain Res. 12, 74–85 (1969).

    Article  PubMed  CAS  Google Scholar 

  65. Stevens, W., Grosser, B. I., Reed, D. J.: Corticosterone-binding molecules in rat brain cytosols: regional distribution. Brain Res. 35, 602–607 (1971).

    Article  PubMed  CAS  Google Scholar 

  66. Taylor, J. M., Levy, W. A., Herzog, I., Scheinberg, L. C: Prevention of experimental cerebral edema by corticosteroids. Neurology 15, 667–674 (1965).

    PubMed  CAS  Google Scholar 

  67. McCoy, G, Scheinberg, L.: Prevention of cerebral edema induced by triethyltin in rabbits by cortico-steroids. Nature 204, 891–892 (1964).

    Article  PubMed  Google Scholar 

  68. Timiras, P. S., Woodbury, D. M., Goodman, L. S.: Effect of adrenalectomy, hydrocortisone acetate, and desoxycorticosterone acetate on brain excitability and electrolyte distribution in mice. J. Pharmacol, exp. Ther. 112, 80–93 (1954).

    CAS  Google Scholar 

  69. Torack, R., Gordon, J., Prokop, J.: PathobioJogy of acute triethyltin intoxication. Int. Rev. Neurobiol. 12, 45–86 (1970).

    Article  PubMed  CAS  Google Scholar 

  70. Touchstone, J. C, Kasparow, M., Hughes, P. A., Horwitz, M. R.: Corticosteroids in human brain. Steroids 7, 205–211 (1966).

    Article  PubMed  CAS  Google Scholar 

  71. Uete, T., Nishimura, S.: The effect of the administration of Cortisol on the levels of Cortisol and electrolytes in blood and cerebrospinal fluid in man. Metabolism 20Metabolism, 319–325 (1971).

    Article  Google Scholar 

  72. Ohya, H., Shimomura, T., Tatebayashi, Y.: Corticosteroid levels in blood and cerebrospinal fluid in various diseases. J. clin. Endocr. 30, 208–214 (1970).

    Article  Google Scholar 

  73. Walker, M. D., Henkin, R. I., Harlan, A. B., Casper, A. G. T.: Distribution of tritiated Cortisol in blood, brain, CSF and other tissues of the cat. Endocrinology 88, 224–232 (1971).

    Article  PubMed  CAS  Google Scholar 

  74. Withrow, C. D., Woodbury, D. M.: Direct and indirect effects of desoxycorticosterone (DOC) on skeletal muscle electrolyte and acid-base metabolism. First Int. Congr. Horm. Steroids 1, 503–513 (1964).

    Google Scholar 

  75. Woodbury, D. M.: Effects of hormones on brain excitability and electrolytes. Recent Progr. Hormone Res. 10, 65–107 (1954).

    CAS  Google Scholar 

  76. Woodbury, D. M.: Relation between the adrenal cortex and the central nervous system. Pharmacol. Rev. 10, 275–357 (1958).

    PubMed  CAS  Google Scholar 

  77. Woodbury, D. M.: Biochemical effects of adrenocortical steroids on the central nervous system. In: Handbook of Neurochemistry, Vol. 7, Chapter 13, pp. 255–287. Lajtha, A. (Ed.), Plenum Press 1972.

    Google Scholar 

  78. Woodbury, D. M. Davenport, V. D.: Brain and plasma cations and experimental seizures in normal and desoxycorticosterone treated rats. Amer. J. Physiol. 157, 234–240 (1949).

    CAS  Google Scholar 

  79. Woodbury, D. M. Koch, A.: Effects of aldosterone and desoxycorticosterone on tissue electrolytes. Proc. Soc. exp. Biol. 94, 720–723 (1957).

    PubMed  CAS  Google Scholar 

  80. Woodbury, D. M. Timiras, P. S., Vernadakis, A.: Influence of adrenocortical steroids on brain function and metabolism. In: Hormones, Brain Function and Behavior, pp. 27–54. Hoagland, H. (Ed.), New York: Academic Press 1957.

    Google Scholar 

  81. Zarrow, M. X., Philpott, J. E., Denenberg, V. H.: Passage of 14C-4-corticosterone from the rat mother to the foetus and neonate. Nature 226, 1058–1059 (1970).

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pharmacology, College of Medicine, University of Utah, Salt Lake City, UT, 84112, USA

    C. D. Withrow & Dixon M. Woodbury

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  1. Neurochirurgische Universitätsklinik Mainz, 6500, Mainz, Langenbeckstr. 1, W. Germany

    H. J. Reulen  & K. Schürmann  & 

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Withrow, C.D., Woodbury, D.M. (1972). Some Aspects of the Pharmacology of Adrenal Steroids and the Central Nervous System. In: Reulen, H.J., Schürmann, K. (eds) Steroids and Brain Edema. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65448-0_5

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  • DOI: https://doi.org/10.1007/978-3-642-65448-0_5

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