Glutamine Synthetase Inhibition Prevents Cerebral Oedema During Hyperammonemia

  • H. Takahashi
  • R. C. Koehler
  • S. W. Brusilow
  • R. J. Traystman
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 51)


The relationship between cerebral oedema and cerebral glutamine accumulation was investigated during acute hyperammonemia in anesthetized rats. Six hours of ammonium acetate infusion resulted in an increase in cortical glutamine concentration and a decrease in specific gravity. Pretreatment with methionine sulfoximine inhibited glutamine synthetase, prevented the increase in glutamine during hyperammonemia, and prevented the decrease in specific gravity. We conclude that the increase in brain water content is linked to the glutamine accumulation derived from the detoxification of ammonia by glutamine synthetase.


Glutamine Synthetase Brain Water Content Carbamyl Phosphate Urea Cycle Enzyme Plasma Ammonium Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Brusilow SW, Batshaw ML, Waber L (1982) Neonatal hyperammonemic coma. Adv Pediatr 29: 69–103PubMedGoogle Scholar
  2. 2.
    Brusilow SW, Traystman RJ (1986) Letter to the Editor. N Engl J Med 314: 786PubMedGoogle Scholar
  3. 3.
    Butterworth RF, Giguere JF, Michaud J, Lavoie J, Layrargues GP (1987) Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem Pathol 6: 1–12PubMedCrossRefGoogle Scholar
  4. 4.
    Cooper AJL, Plum F (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67: 440–519PubMedGoogle Scholar
  5. 5.
    Marmarou A, Poll W, Shulman K, Bhagavan H (1978) A simple gravimetric technique for measurement of cerebral edema. J Neurosurg 49: 530–537PubMedCrossRefGoogle Scholar
  6. 6.
    Norenberg MD, Martinez-Hernandez A (1979) Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 161: 303–310PubMedCrossRefGoogle Scholar
  7. 7.
    Pilbeam CM, McD Anderson R, Bhathal PS (1983) The brain in experimental portal-systemic encephalopathy. II. Water and electrolyte changes. J Pathol 140: 347–355PubMedCrossRefGoogle Scholar
  8. 8.
    Rao SLN, Meister A (1972) In vivo formation of methionine sulfoximine phosphate, a protein bound metabolite of methonine sulfoximine. Biochemistry 11: 1123–1127PubMedCrossRefGoogle Scholar
  9. 9.
    Shaywitz AB, Rothstein P, Venes JL (1980) Monitoring and management of increased intracranial pressure in Reye syndrome: Result in 29 children. Pediatrics 66: 198–204PubMedGoogle Scholar
  10. 10.
    Zimmerman S, Bachman C, Columbo J (1981) Ultrastructural pathology in congenital defects of the urea cycle: ornithine transcarbamylase and carbamyl phosphate synthetase deficiency. Virchows Arch [A] 393: 321–331CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • H. Takahashi
    • 1
  • R. C. Koehler
    • 2
  • S. W. Brusilow
    • 1
  • R. J. Traystman
    • 1
  1. 1.Department of Anesthesiology/Critical Care Medicine, and PediatricsThe Johns Hopkins Medical InstitutionBaltimoreUSA
  2. 2.Department of Anesthesiology & Critical Care MedicineThe Johns Hopkins HospitalBaltimoreUSA

Personalised recommendations