Metabolic Brain Disease

, Volume 20, Issue 4, pp 303–318 | Cite as

Mechanisms of Ammonia-Induced Astrocyte Swelling

  • M. D. NorenbergEmail author
  • K. V. Rama Rao
  • A. R. Jayakumar


Astrocyte swelling represents the major factor responsible for the brain edema associated with fulminant hepatic failure (FHF). The edema may be of such magnitude as to increase intracranial pressure leading to brain herniation and death. Of the various agents implicated in the generation of astrocyte swelling, ammonia has had the greatest amount of experimental support. This article reviews mechanisms of ammonia neurotoxicity that contribute to astrocyte swelling. These include oxidative stress and the mitochondrial permeability transition (MPT). The involvement of glutamine in the production of cell swelling will be highlighted. Evidence will be provided that glutamine induces oxidative stress as well as the MPT, and that these events are critical in the development of astrocyte swelling in hyperammonemia.


Ammonia glutamine cell swelling oxidative stress mitochondrial permeability transition aquaporin-4 lactate peripheral benzodiazepine receptor neurosteroids glutathione 


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • M. D. Norenberg
    • 1
    • 2
    • 3
    • 4
    Email author
  • K. V. Rama Rao
    • 2
  • A. R. Jayakumar
    • 2
  1. 1.Veterans Affairs Medical CenterMiamiFlorida
  2. 2.Department of PathologyUniversity of Miami School of MedicineMiami
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of Miami School of MedicineMiami
  4. 4.Department of Pathology (D-33)University of Miami School of MedicineMiami

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