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Updated: May 25, 2026

Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Theories of the pathogenesis of hepatic encephalopathy
E Anthony Jones1, Kevin D Mullen
1Division of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109, USA.
Abstract:
The earliest hypothesis of the pathogenesis of HE implicated ammonia, although effects of appreciable concentrations of this neurotoxin did not resemble HE. Altered eurotransmission in the brain was suggested by similarities between increased GABA-mediated inhibitory neurotransmission and HE, specifically decreased consciousness and impaired motor function. Evidence of increased GABAergic tone in models of HE has accumulated; potential mechanisms include increased synaptic availability of GABA and accumulation of natural benzodiazepine receptor ligands with agonist properties. Pathophysiological concentrations of ammonia associated with HE, have the potential of enhancing GABAergic tone by mechanisms that involve its interactions with the GABAa receptor complex.
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