Cerebral Protection With Barbiturates, Nizofenone and Steroids

  • Shinya Manaka
  • Takaaki Kirino
  • Mamoru Sasaki


Steroids and barbiturates have been considered to be very reasonable drugs for cerebral protection from ischemic or traumatic insult. However, controversies on the effectiveness of these drugs have been growing [1–3]. On one hand there are experimental studies which strongly support the utility of these drugs for cerebral trauma or ischemia, but recent clinical studies based on randomized well-controlled trials have failed to show any advantages for these drugs [4–8]. The initial clinical enthusiasm for the widespread application of barbiturates to protects the brain from head injury, circulatory arrest, asphyxia, or ischemia has almost disappeared. Clinical and experimental data showed that complete global ischemic injury has not been favorably altered by barbiturate coma therapy, while barbiturates do appear to protect the brain damage from focal or incomplete ischemia/hypoxia [2,3]. If barbiturates are given before permanent occlusion, the size of the ensuing infarct is significantly reduced [9]. Barbiturate protection from cerebral ischemia/hypoxia is, at least partially, the result of a depressed metabolic demand for oxygen. Astrup demonstrated that the metabolic depression resulted from inhibition of neurotransmission [10].


Head Injury Middle Cerebral Artery Occlusion Severe Head Injury Mongolian Gerbil Neuronal Density 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bircher NG (1985) Ischemic brain protection. Ann Emerg Med 14: 784–788PubMedCrossRefGoogle Scholar
  2. 2.
    Hoff JT (1966) Cerebral protection. J Neurosurg 65: 579–591Google Scholar
  3. 3.
    Newberg LA (1984) Cerebral Resuscitation; advances and controversies. Ann Emerg Med 13: 853–856PubMedCrossRefGoogle Scholar
  4. 4.
    Braakman R, Shouten HJA, Dishoeck MB, Minderhoud JM (1983) Megadose steroids in severe head injury. J Neurosurg 58: 326–330PubMedCrossRefGoogle Scholar
  5. 5.
    Cooper PR, Moody S, Clark WK, Kirkpatrick J, Maravilla K, Gould AL, Drane W (1979) Dexamethasone and sever head injury, a prospective double-blind study. J Neurosurg 51: 307–316PubMedCrossRefGoogle Scholar
  6. 6.
    Dearden NM, Gibson JS, McDowall DG, Gibson RM, Cameron MM (1986) Effect of high-dose dexamethasone on outcome from severe head injury. J Neurosurg 64: 81–88PubMedCrossRefGoogle Scholar
  7. 7.
    Grafton GT (1988) Steroids after cardiac arrest: A retrospective study with concurrent, nonrandomized controls. Neurology 38: 1315–1316PubMedGoogle Scholar
  8. 8.
    Ward JD, Becker DP, Miller JD, Choi SC, Marmarou A, Wood C, Newlon PG, Keenan R (1985) Failure of prophylactic barbiturate coma in the treatment of severe head injury. J Neurosurg 62: 283–388Google Scholar
  9. 9.
    Michenfelder JD, Milde JH, Sundt TJ Jr (1976) Cerebral protection by barbiturate anesthesia. Use after middle cerebral artery occlusion in Java monkeys. Arch Neurol 33: 345–350PubMedCrossRefGoogle Scholar
  10. 10.
    Astrup J (1982) Energy-requiring cell functions in the ischemic brain, their critical supply and possible inhibition in protective therapy. J Neurosurg 56: 482–497PubMedCrossRefGoogle Scholar
  11. 11.
    Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker MD, and the Comprehensive Central Nervous System Trauma Centers (1988) High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg 69: 15–23Google Scholar
  12. 12.
    Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69PubMedCrossRefGoogle Scholar
  13. 13.
    Kirino T, Tamura A, Sano K (1986) A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17: 455–459PubMedCrossRefGoogle Scholar
  14. 14.
    Akiten PG, Schiff SJ (1986) Barbiturate protection against hypoxic neuronal damage in vitro. J Neurosurg 65: 230–232CrossRefGoogle Scholar
  15. 15.
    Kirino T, Tamura A, Tomukai N, Sano K (1986) Treatable ischemic neuronal damage in the gerbil hippocampus. Brain and Nerve 38: 1157–1163PubMedGoogle Scholar
  16. 16.
    Benveniste HB, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43: 1369–1374PubMedCrossRefGoogle Scholar
  17. 17.
    Tamura A, Asano T, Sano K, Tsumagari T, Nakajima A (1979) Protection from cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital. A comparative study in chronic middle cerebral artery occlusion in cats. Stroke 10: 126–134PubMedCrossRefGoogle Scholar
  18. 18.
    Saito I, Asano T, Ochiai C, Takakura K. Tamura A, Sano K (1983) A double-blind clinical evaluation of the effect of nizofenone (Y-9179) on delayed ischemic neurological deficits following aneurysmal rupture. Neurol Res 5: 29–47PubMedGoogle Scholar
  19. 19.
    Ohta T, Kikuchi H, Hashi K, Kudo Y (1986) Nizofenone administration in the acute stage following subarachnoid hemorrhage. J Neurosurg 64: 420–426PubMedCrossRefGoogle Scholar
  20. 20.
    Watanabe H (1985) Brain protection in head injury and cerebrovascular disease by nizofenone. Rinsho-iyaku 1: 307–313Google Scholar
  21. 21.
    Ochiai C, Asano T, Tamura A, Sano K, Fukuda T and Nakamura T (1981) An experimental study on the mechanism of the protective action of pentobarbital and Y-9179 against cerebral ischemia. Neurol Med Chir (Tokyo) 21: 303–311CrossRefGoogle Scholar
  22. 22.
    Sasaki M, Manaka S, Takakura K (1987) Time course of the cerebroprotective effect of dexamethasone in the experimental head injury. Brain and Nerve 39: 155–161PubMedGoogle Scholar
  23. 23.
    Braughler JM, Hall ED (1985) Current application of “high-dose” steroid the therapy for INS injury, a pharmacological perspective. J Neurosurg 62: 806–810PubMedCrossRefGoogle Scholar
  24. 24.
    Jane JA, Rimel RW, Pobereskin LH (1982) Outcome and pathology of head injury. In: Grossman RG, Gildenberg PL (eds) head injury: Basic and clinical aspects. Raven, New York, pp. 229–237Google Scholar
  25. 25.
    Giannotta SL Weiss MH Apuzzo Mil, Martin E (1984) High dose glucocorticoids in the management of severe head injury. Neurosurgery 15: 497–501Google Scholar
  26. 26.
    Hall ED (1985) High-dose glucocorticoid treatment improves neurological recovery in head-injured mice. J Neurosurg 62: 882–887PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Shinya Manaka
    • 1
  • Takaaki Kirino
    • 2
  • Mamoru Sasaki
    • 3
  1. 1.Department of NeurosurgeryIchihara Hospital, Teikyo University, School of MedicineIchiharaJapan
  2. 2.Department of NeurosurgeryTeikyo University School of MedicineTokyo, 173Japan
  3. 3.Department of NeurosurgeryTeraoka Memorial HospitalShinichi-machi, HiroshimaJapan

Personalised recommendations