Abstract
Ammonia (NH4 +) has been implicated since the 1950’s as the primary pathogenic agent contributing to the encephalopathies associated with hepatic failure1. NH4 + is clearly neurotoxic, but the molecular mechanisms by which ammonia exerts its toxic actions remain the subject of active investigation. Because the primary neurologic manifestations of these encephalopathies are consistent with central nervous system depression, increased activity of neuronal pathways using the principle inhibitory neurotransmitter, γ-aminobutyric acid (GABA) appeared likely to contribute to the pathogenesis of these syndromes. Despite ample evidence for the presence of both increased GABAergic neurotransmission and elevated NH4 + concentrations in the brain during hepatic failure, these two pathogenic mechanisms appear to be mutually exclusive. However, recent investigations suggest that these two pathogenic mechanisms are linked, in that NH4 + may enhance GABAergic neurotransmission by directly interacting with the GABAA receptor at pathophysiologically relevant concentrations. These new findings not only have important implications for the mechanisms contributing to the encephalopathies associated with hepatic failure and congenital hyperammonemia syndromes, but may provide a locus for the development of new treatment modalities.
Keywords
- Hepatic Encephalopathy
- Ammonium Salt
- GABAergic Neurotransmission
- Ammonium Tartrate
- Central Nervous System Depression
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.
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Ha, JH., Knauer, S., Moody, E., Jones, E.A., Basile, A.S. (1997). Direct Enhancement of Gaba-Ergic Neurotransmission by Ammonia. 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_6
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DOI: https://doi.org/10.1007/978-1-4615-5945-0_6
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