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New concepts in the mechanism of ammonia-induced astrocyte swelling

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Abstract

It is generally accepted that astrocyte swelling forms the major anatomic substrate of the edema associated with acute liver failure (ALF) and that ammonia represents a major etiological factor in its causation. The mechanisms leading to such swelling, however, remain elusive. Recent studies have invoked the role of oxidative stress in the mechanism of hepatic encephalopathy (HE), as well as in the brain edema related to ALF. This article summarizes the evidence for oxidative stress as a major pathogenetic factor in HE/ALF and discusses mechanisms that are triggered by oxidative stress, including the induction of the mitochondrial permeability transition (MPT) and activation of signaling kinases. We propose that a cascade of events initiated by ammonia-induced oxidative stress results in cell volume dysregulation leading to cell swelling/brain edema. Blockade of this cascade may provide novel therapies for the brain edema associated with ALF.

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Acknowledgments

This work was supported by the Department of Veterans Affairs and NIH Grant No. DK063311. K.V.R. and A.R.J. are recipients of the American Association for the Study of Liver Disease/American Liver Foundation Grants.

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  1. K. S. Panickar

    Present address: Nutrient Requirements & Functions Laboratory, Beltsville Human Nutrition Research Center, United States Department of Agriculture, Beltsville, MD, 20705, USA

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  1. Veterans Affairs Medical Center, Miami, FL, 33101, USA

    M. D. Norenberg

  2. Department of Pathology, University of Miami School of Medicine, Miami, FL, 33101, USA

    M. D. Norenberg, A. R. Jayakumar, K. V. Rama Rao & K. S. Panickar

  3. Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL, 33101, USA

    M. D. Norenberg

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Norenberg, M.D., Jayakumar, A.R., Rama Rao, K.V. et al. New concepts in the mechanism of ammonia-induced astrocyte swelling. Metab Brain Dis 22, 219–234 (2007). https://doi.org/10.1007/s11011-007-9062-5

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