Increased extracellular brain glutamate in acute liver failure: decreased uptake or increased release?
Glutamatergic dysfunction has been suggested to play an important role in the pathogenesis of hepatic encephalopathy (HE) in acute liver failure (ALF). Increased extracellular brain glutamate concentrations have consistently been described in different experimental animal models of ALF and in patients with increased intracranial pressure due to ALF. High brain ammonia levels remain the leading candidate in the pathogenesis of HE in ALF and studies have demonstrated a correlation between ammonia and increased concentrations of extracellular brain glutamate both clinically and in experimental animal models of ALE Inhibition of glutamate uptake or increased glutamate release from neurons and/or astrocytes could cause an increase in extracellular glutamate. This review analyses the effect of ammonia on glutamate release from (and uptake into) both neurons and astrocytes and how these pathophysiological mechanisms may be involved in the pathogenesis of HE in ALF.
Rose
Christopher
C
Department of Cellular Neurosciences, Max-Delbrück Center for Molecular Medicine, Robert-Rössle Str. 10, Berlin 13122. Germany. c.rose@mdc-berlin.de
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000378:metabolism*
D018698:Glutamic Acid