Advertisement

Journal of Neurology

, Volume 220, Issue 3, pp 199–209 | Cite as

The response of focal ischemic cerebral edema to dexamethasone

  • A. Fenske
  • M. Fischer
  • F. Regli
  • U. Hase
Original Investigations

Summary

Twenty-four h after permanent occlusion of the middle cerebral artery (MCA) in the cat, the hemispheric swelling due to edema is markedly reduced under treatment with large doses of dexamethasone than is the case with the untreated group. The increase of regional water and sodium content in the MCA territory is less in the dexamethasone treated group, whereas the potassium changes in the ischemic tissue showed only small differences between the two groups. The potassium content of the non-ischemic tissue is slightly increased in the dexamethasone treated animals when comparing with the untreated group. RISA activity in the tissue is increased in the grey and the white matter of both groups. The less marked RISA−131 activity in the cortical grey matter of the treated animals indicates blood-brain barrier damage of a smaller degree due to dexamethasone. These findings indicate a beneficial effect of dexamethasone on local ischemic edema. Regarding our results and the pharmacokinetics of this steroid the dexamethasone loading of a patient has to be in the range of about 100 mg per day for the adult, and has to be started immediately after the onset of a stroke.

Key words

Ischemia focal Cerebral edema Blood-brain barrier Dexamethasone Stroke 

Zusammenfassung

Vierundzwanzig Stunden nach permanentem Verschluß der Arteria cerebri media der Katze ist die ödembedingte Volumenzunahme der geschädigten Hemisphäre unter hochdosierter Dexamethasonbehandlung gegenüber nichtbehandelten Tieren deutlich geringer. Auch der Vergleich der regionalen Wasser- und Natriumzunahme ergibt für die behandelten Tiere geringere Werte. Gleichzeitig findet sich ein nur geringerer Kaliumverlust aus dem geschädigten Gewebe, während sich unter Dexamethasongabe in den ungeschädigten Hirnregionen eine erhöhte Kaliumkonzentration nachweisen läßt. Die RISA−131-Aktivität im Hirngewebe, Indikator für eine Blut-Hirn-Schrankenschädigung, ist 24 h nach Ischämiebeginn sowohl in der grauen als auch der weißen Substanz in beiden Gruppen erhöht, wobei das Ausmaß der BHS-Schädigung im betroffenen Cortexareal der behandelten Gruppe gegenüber den Kontrollen wiederum geringer ist. Diese Befunde sprechen unter Berücksichtigung der Pharmakokinetik des Steroids für eine günstige Wirkung bei der Therapie des lokalen ischämischen Hirnödems. Voraussetzung scheint jedoch die frühzeitige, hochdosierte Steroidgabe zu sein, wobei eine Tagesdosis entsprechend über 100 mg Dexamethason beim erwachsenen Menschen erreicht werden sollte.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Allen, N.: The chemical basis of neurological disorders. Clin. Neurosurg.14, 386–423 (1967)Google Scholar
  2. 2.
    Atkinson, D. E.: The energy charge of the adenylate pool as a regulatory parameter. Interaction with feed back modifiers. Biochemistry7, 4030–4034 (1968)Google Scholar
  3. 3.
    Aulich, A., Fenske, A.: Das Computertomogramm des Schlaganfalls. Akt. Neurol.4, 129–140 (1977)Google Scholar
  4. 4.
    Baethmann, A., Lanksch, W., Schmiedek, P.: Formation and treatment of cerebral edema. Neurochirurgica17, 37–47 (1974)Google Scholar
  5. 5.
    Barlow, C. F.: Physiology and pathophysiology of protein permeability in the central nervous system. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 139–146. Berlin-Heidelberg-New York: Springer 1972Google Scholar
  6. 6.
    Bartko, D., Reulen, H. J., Koch, H., Schürmann, K.: Effect of dexamethasone on the early edema following occlusion of the middle cerebral artery in cats. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 127–137. Berlin-Heidelberg-New York: Springer 1972Google Scholar
  7. 7.
    Bauer, R. B., Tellez, H.: Dexamethasone as treatment in cerebrovascular disease. A control study in acute cerebral infarction. Stroke4, 547–555 (1973)Google Scholar
  8. 8.
    Gandelise, L., Colombo, A., Spinnler, H.: Therapy against brain swelling in stroke patients. Stroke6, 353–356 (1975)Google Scholar
  9. 9.
    Torre, J. C. de la, Surgeon, J. W.: Dexamethasone and DMSO in experimental transorbital cerebral infarction. Stroke7, 577–583 (1976)Google Scholar
  10. 10.
    Donley, R. F., Sundt, T. M.: The effect of dexamethasone on the edema of focal cerebral ischemia. Stroke4, 148–155 (1973)Google Scholar
  11. 11.
    Elliot, K., Jaspers, H.: Measurement of experimentally induced brain swelling and shrinkage. Am. J. Physiol.157, 122–129 (1949)Google Scholar
  12. 12.
    Fenske, A., Samii, M., Reulen, H. J., Hey, O.: Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced edema. Acta neurochir.28, 81–94 (1973)Google Scholar
  13. 13.
    Fenske, A., Kohl, J., Fischer, M., Regli, F., Reulen, H. J.: The effect of arterial hypertension following occlusion of the middle cerebral artery. In: Blood flow and metabolism in the brain, A. M. Harper et al., eds., pp. 25–26. Edinburgh-London-New York: 1975Google Scholar
  14. 14.
    Fenske, A., Reulen, H. J.: Pharmakokinetic studies of dexamethasone in edematous brain tissue. In preparationGoogle Scholar
  15. 15.
    Fujimoto, T., Walker, J. T. Jr., Spatz, M., Klatzo, I.: Pathophysiologic aspects of ischemic edema. In: Dynamics of brain edema, H. M. Pappius, W. Feindel, eds., pp. 171–180. Berlin: Springer 1976Google Scholar
  16. 16.
    Garcia, J. H., Cox, J. V., Hudgins, W. R.: Ultrastructure of the microvasculature in experimental cerebral infarction. Acta neuropath.18, 273–285 (1971)Google Scholar
  17. 17.
    Hoppe, W. E., Waltz, A. G., Jordan, M. J., Chem, B., Jacobson, R. L.: Effects of dexamethasone on distribution of water and pertechnetate in brains of cats after middle cerebral artery occlusion. Stroke5, 617–622 (1974)Google Scholar
  18. 18.
    Hudgins, W. R., Garcia, J. H.: Transorbital approach to the middle cerebral artery of the squirrel monkey: a technique for experimental cerebral infarction applicable to ultrastructural studies. Stroke1, 107–111 (1970)Google Scholar
  19. 19.
    Ito, U., et al.: Cerebral changes during recirculation following temporary ischemia in Mongolian gerbils. Neurol. Med. Chirurg.16, 313–322 (1976)Google Scholar
  20. 20.
    Klatzo, I.: Neuropathological aspects of brain edema. Presidential address. J. Neuropath. exp. Neurol.26, 1–14 (1967)Google Scholar
  21. 21.
    Klatzo, I.: Pathophysiological aspects of brain edema. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 1–8. Berlin-Heidelberg-New York: Springer 1972Google Scholar
  22. 22.
    Kogure, K., Busto, R., Scheinberg, D., Reinmuth, O.: Energy metabolits and water content in rat brain during the early stage of development of cerebral infarction. Brain97, 103–114 (1974)Google Scholar
  23. 23.
    Lee, C. J.: Evaluation in the concept of the blood-brain barrier phenomenon. In: Progress in neuropathology, H. M. Zimmermann, ed., Vol. I, pp. 84–145. New York-London: Grune and Stratton 1971Google Scholar
  24. 24.
    Lee, M. C., Mastri, A. R., Waltz, A. G., Loewenson, R. B.: Ineffectiveness of dexamethasone for treatment of experimental cerebral infarction. Stroke5, 215–218 (1974)Google Scholar
  25. 25.
    Lky, N., Nimmannitya, J.: Massive cerebral infarction with severe brain swelling. Stroke1, 158–163 (1970)Google Scholar
  26. 26.
    Little, R. J., Kerr, W. L. F., Sundt, T. M. Jr.: Significance of neuronal alterations in developing cortical infarction. Mayo Clin. Proc.49, 827–836 (1974)Google Scholar
  27. 27.
    Little, J. R., Kerr, F. W. L., Sundt, T. M. Jr.: Microvasculatory abstruction in focal cerebral ischemia. An electronmicroscopic investigation in monkeys. Stroke7, 25–30 (1976)Google Scholar
  28. 28.
    Long, D. M., Hartmann, J. F., French, L. A.: The response of experimental cerebral edema to glucosteroid administration. J. Neurosurg.24, 843–854 (1966)Google Scholar
  29. 29.
    O'Brien, M. D., Waltz, A. G.: Transorbital approach for occluding the middle cerebral artery without craniotomy. Stroke4, 201–206 (1973)Google Scholar
  30. 30.
    O'Brien, M. D., Waltz, A. G.: Ischemic cerebral edema. Arch. Neurol.30, 456–460 (1974)Google Scholar
  31. 31.
    O'Brien, M. D., Jordan, M. M., Waltz, A. G.: Ischemic cerebral edema and the blood-brain barrier. Arch. Neurol.30, 461–465 (1974)Google Scholar
  32. 32.
    Olsson, Y., Crowell, R. M., Klatzo, I.: The blood-brain barrier to protein tracers in focal cerebral ischemia and infarction caused by occlusion of the middle cerebral artery. Acta neuropath.18, 89–102 (1971)Google Scholar
  33. 33.
    Pappius, H. M.: Biochemical studies on experimental brain edema. In: Brain edema, I. Klatzo, F. Seitelberger, eds., pp. 445–460. New York: Springer 1967Google Scholar
  34. 34.
    Pappius, H. M.: Effects of steroids on cold injury edema. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 57–63. Berlin-Heidelberg-New York: Springer (1972)Google Scholar
  35. 35.
    Patten, B. M., Mendell, J., Bruun, B., et al.: Double-blind study of the effects of dexamethasone on acute stroke. Neurology22, 377–383 (1972)Google Scholar
  36. 36.
    Plum, F., Alvord, E. C., Posner, J. B.: Effect of steroids on experimental cerebral infarction. Arch. Neurol.9, 571–573 (1963)Google Scholar
  37. 37.
    Regli, F., Yamaguchi, T., Waltz, A. G.: Effects of vasodilating drugs on blood flow and the microvasculature of ischemic and nonischemic cerebral cortex. Arch. Neurol.24, 467–474 (1971)Google Scholar
  38. 38.
    Reulen, H. J., Steude, U., Brendel, H., et al.: Energetische Störung des Kationentransportes als Ursache des intrazellulären Hirnödems. Acta neurochir.22, 129–166 (1970)Google Scholar
  39. 39.
    Reulen, H. J., Hadjidimos, A., Schürmann, K.: The effect of dexamethasone on water and electrolyte content and on rCBF in perifocal brain edema in man. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 239–252. Berlin-Heidelberg-New York: Springer 1972Google Scholar
  40. 40.
    Reulen, H. J.: Vasogenic brain edema. Brit. J. Anaest.48, 741–752 (1976)Google Scholar
  41. 41.
    Rubinstein, M. K.: The influence of adrenocortical steroids on severe cerebrovascular accidents. J. Nerv. Ment. Dis.141, 291–299 (1965)Google Scholar
  42. 42.
    Westergaard, E., Go, G., Klatzo, I., et al.: Increased permeability of cerebral vessles to horseradish peroxidase induced by ischemia in Mongolian gerbils. Acta neuropath.35, 307–325 (1976)Google Scholar
  43. 43.
    Withrow, C. D., Woodbury, D. M.: Some aspects of the pharmacology of adrenal steroids and the central nervous system. In: Steroids and brain edema, H. J. Reulen, K. Schürmann, eds., pp. 41–55. Berlin-Heidelberg-New York: Springer 1972Google Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • A. Fenske
    • 1
  • M. Fischer
    • 1
  • F. Regli
    • 2
  • U. Hase
    • 3
  1. 1.Department of NeurologyUniversity Hospital, MainzMainzGermany
  2. 2.Head of the Department of NeurologyUniversity LausanneLausanneSwitzerland
  3. 3.Department of NeurosurgeryUniversity Hospital MainzMainzGermany

Personalised recommendations