Neurochemical Pathology

, Volume 6, Issue 1–2, pp 131–144 | Cite as

Cerebral GABA-ergic and glutamatergic function in hepatic encephalopathy

  • Roger F. Butterworth
  • Joël Lavoie
  • Jean-François Giguère
  • Gilles Pomier Layrargues
  • Marcelle Bergeron


Measurement of amino acids in brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma revealed a threefold increase in glutamine and a concomitant decrease in brain glutamate. The GABA levels were found to be unaltered. Studies using an animal model of portal-systemic encephalopathy gave similar results. Glutamic acid decarboxylase (GAD) activities were within normal limits, both in the brains of cirrhotic patients and portocaval-shunted rats. A previous study reported normal [3H]GABA binding to synaptic membrane preparations from cerebral cortex in these animals. Taken together, these findings suggest that cerebral GABA function is not impaired in hepatic encephalopathy associated with chronic liver disease and portal-systemic shunting. On the other hand, there is evidence to suggest that the releasable pool ofglutamate may be depleted in brain in hepatic encephalopathy. Data consistent with this hypothesis include: (i) Reduction in the evoked release of endogenous glutamate by superfusion of hippocampal slices with pathophysiological levels of ammonia; (ii) ammonia-induced reduction of glutamatergic neurotransmission; and (iii) an increase in the number of [3H]glutamate binding sites in synaptic membrane preparations from hyperammonemia rats and from rats with portocaval shunts. Such neurochemical changes may be of pathophysiological significance in hepatic encephalopathy.

Index Entries

Hepatic encephalopathy portocaval anastomosis GABA glutamate glutamic acid decarboxylase 


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Copyright information

© The Humana Press Inc. 1987

Authors and Affiliations

  • Roger F. Butterworth
    • 1
  • Joël Lavoie
    • 1
  • Jean-François Giguère
    • 1
  • Gilles Pomier Layrargues
    • 2
  • Marcelle Bergeron
    • 1
  1. 1.Laboratory of Neurochemistry, André-Viallet Clinical Research Center, Hôpital Saint-LucUniversity of MontrealCanada
  2. 2.Liver Unit, André-Viallet Clinical Research Center, Hôpital Saint-LucUniversity of MontrealCanada

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