Pathogenesis of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome during the course of acute or chronic liver disease. It is functional in nature, potentially reversible and precipitated by rather heterogeneous factors. At the neurophysiological level HE is characterized by a low frequent cortico-cortical electrical coupling, which may explain the cognitive deficits and a low frequent corticomuscular coupling, which may explain the fine motor deficits. Current evidence suggests that HE is the consequence of a low grade chronic glial edema with subsequent alterations of glioneuronal communication. Different factors, such as ammonia, benzodiazepines, inflammatory cytokines can induce or aggravate astrocyte swelling, which results in the activation of osmosignaling cascades, protein modifications, alterations in gene expression and neurotransmission. Among the protein modifications nitration of critical tyrosine residues in glial proteins may play an important role. Several proteins, which are nitrated in response to ammonia, benzodiazepines, hypoosmotic astrocyte swelling or inflammatory cytokines have been identified, including glutamine synthetase and the peripheral type benzodiazepine receptor.