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Semin Liver Dis 2003; 23(3): 251-258
DOI: 10.1055/s-2003-42643
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Molecular Neurobiology of Acute Liver Failure

Roger F. Butterworth
  • Director, Neuroscience Research Unit Hôpital Saint-Luc (CHUM) Montreal, Québec Canada
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Publication History

Publication Date:
02 October 2003 (online)

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ABSTRACT

Acute liver failure results in encephalopathy and brain edema that is characterized by astrocytic cell swelling. Molecular biological techniques have led to the identification of alterations in expression of several genes coding for key astrocytic proteins in acute liver failure. Such proteins include amino acid transporters, structural proteins, the endothelial cell glucose transporter GLUT-1, the mitochondrial “peripheral-type” benzodiazepine receptor, and the water channel protein aquaporin IV. Magnetic resonance spectroscopic studies reveal increased brain lactate concentrations that are positively correlated with severity of encephalopathy and brain edema in acute liver failure, suggesting a deficit of cellular oxidative capacity and impending brain energy failure. Mild hypothermia prevents brain edema in acute liver failure, and mechanisms responsible for this beneficial effect include reduced blood-brain ammonia transfer as well as normalization of astrocytic amino acid transport and brain energy metabolism. Further elucidation of the molecular mechanisms responsible for brain edema and encephalopathy in acute liver failure will undoubtedly lead to novel treatment strategies for these complications.

KEYWORDS

Acute liver failure - brain edema - gene expression - ammonia - brain energy metabolism - astrocytes - transporters - osmoregulation - hypothermia

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