Neurochemical studies of hepatic encephalopathy

Abstract

Despite intensive research, the neurochemical basis of hepatic encephalopathy (HE) has not been defined. Theories that are currently favoured to explain the cerebral dysfunction that accompanies acute or chronic hepatic failure include: (1) ammonia acting as the putative neurotoxin; (2) perturbed monoamine neutrotransmission as a result of altered plasmo amino acid metabolism; (3) an imbalance between excitatory amino acid neurotransmission, mediated by glutamate, and inhibitory amino acid neurotransmission, mediated by gamma-aminobutyric acid (GABA); and (4) increased cerebral concentrations of an endogenous benzodiazepine-like substance. Studies of amino acid neurotransmitter receptors in HE have yielded conflicting results. The majority of studies in different animal models of acute and chronic HE and in patients have reported that brain GABA receptor density and affinity are unchanged. There have been fewer studies of excitatory amino acid receptors and these have also yielded conflicting results. However, the majority suggest that components of the glutamate receptor system are perturbed in HE. Further investigation is required to determine the significance of these findings to the pathogenesis of HE.