Alterations in expression of genes coding for key astrocytic proteins in acute liver failure

Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure a s a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammoni a by the brain is the major cause of the central nervous system complicatio ns of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentratio ns or by inhibition of glutamate removal from brain extracellular space. Ac ute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT-1) and glutamate (GLT-1) transporters, the astrocytic str uctural protein glial fibrillary acidic protein (GFAP) the "peripheral-type " benzodiazepine receptor (PTBR) and the water channel protein, aquaporin I V. Loss of expression of GLT-1 results in increased extracellular brain glu tamate in acute liver failure. Experimental acute liver failure also result s in post-translational modifications of the serotonin and noradrenaline tr ansporters resulting in increased extracellular concentrations of these mon oamines Therapeutic measures currently used to prevent an treat brain edema and encephalopathy in patients with acute liver failure include mild hypot hermia and the ammonia-lowering agent L-ornithine-L-aspartate. (C) 2001 Wil ey-Liss, Inc.