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The Involvement of Ammonia with the Mechanisms that Enhance Gaba-Ergic Neurotransmission in Hepatic Failure

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Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 420))

Abstract

There are currently two primary hypotheses regarding the pathogenic mechanisms contributing to the development of hepatic encephalopathy (HE). Ammonia has been implicated in the pathogenesis of the encephalopathies associated with hepatic failure since the 1950’s1. While challenged by other hypotheses over time, the ammonia hypothesis of the pathogenesis of HE has remained dominant. The other main hypothesis postulates a role for increased GABAergic neurotransmission in the development of HE, a concept supported by a large body of evidence that has been accumulating since 19802. Over the years, these hypotheses have had a uneasy, and apparently mutually exclusive relationship. However, recently reported information now makes it appear possible that both elevated levels of ammonia and increased GABAergic neurotransmission are involved in the pathogenesis of HE3,4. Thus, it now appears that these two hypotheses are not mutually incompatible, but essential for the development of the encephalopathy. Furthermore, the new findings suggest a concept that unifies both hypotheses.

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Authors and Affiliations

  1. Department of Gastrointestinal and Liver Diseases, Academic Medical Center, Amsterdam, The Netherlands

    E. Anthony Jones

  2. Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD, 20892, USA

    Anthony S. Basile

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  1. E. Anthony Jones
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  1. Instituto de Investigaciones Citologicas de la F. V. I. B., Valencia, Spain

    Vicente Felipo  & Santiago Grisolía  & 

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Jones, E.A., Basile, A.S. (1997). The Involvement of Ammonia with the Mechanisms that Enhance Gaba-Ergic Neurotransmission in Hepatic Failure. In: Felipo, V., Grisolía, S. (eds) Advances in Cirrhosis, Hyperammonemia, and Hepatic Encephalopathy. Advances in Experimental Medicine and Biology, vol 420. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5945-0_5

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  • DOI: https://doi.org/10.1007/978-1-4615-5945-0_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7724-5

  • Online ISBN: 978-1-4615-5945-0

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