(HE). 1 Despite considerable work by many research groups, however, the mechanism (s) of
ammonia neurotoxicity remains largely unknown. Current views on its pathogenesis include
impaired bioenergetics, altered neurotransmission, electrophysiologic derangements, and
glutamate-mediated excitotoxicity. Indirect effects of ammonia metabolism may also be
involved, particularly the excessive production of glutamine, that may be deleterious to the
central nervous system. 2 Oxidative stress is an evolving concept in the pathogenesis of …

Increased ammonia accumulation in the brain due to liver dysfunction is a major contributor
to the pathogenesis of hepatic encephalopathy (HE). Fatal outcome of rapidly progressing
(acute) HE is mainly related to cytotoxic brain edema associated with astrocytic swelling. An
increase of brain ammonia in experimental animals or treatment of cultured astrocytes with
ammonia generates reactive oxygen and nitrogen species in the target tissues, leading to
oxidative/nitrosative stress (ONS). In cultured astrocytes, ammonia-induced ONS is …