Pathological role for exocytotic glutamate release from astrocytes in hepatic encephalopathy.

Liver failure can lead to generalized hyperammonemia, which is thought to be the underlying cause of hepatic encephalopathy. This neuropsychiatric syndrome is accompanied by functional changes of astrocytes. These glial cells enter ammonia-induced self-amplifying cycle characterized by brain oedema, oxidative and osmotic stress that causes modification of proteins and RNA. Consequently, protein expression and function are affected, including that of glutamine synthetase and plasmalemmal glutamate transporters, leading to glutamate excitotoxicity; Ca(2+)-dependent exocytotic glutamate release from astrocytes contributes to this extracellular glutamate overload.