Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy

A. H. Lockwood, Myron Ginsberg, H. M. Rhoades, M. T. Gutierrez

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Abstract

The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of 'threshold' amounts of ammonia were assessed, Eight weeks after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ranged from 12 to 18%. Unilateral infusions of ammonia did not affect behavior but altered the electroencephalogram and selectively increased the glucose metabolic rate in the thalamus, hypothalamus, and substantia nigra in half of the animals, a pattern similar to that seen after a portacaval shunt, suggesting hyperammonemia as the cause of postshunt increases in glucose metabolism. Visual inspection of autoradiograms, computed correlation coefficients relating interregional metabolism, and principal component analysis suggest that normal cerebral metabolic and functional interrelationships are altered by shunting. Ammonia stimulation of the hypothalamic satiety centers may suppress appetite and lead to cachexia. Reductions in the ammonia detoxification capacity of skeletal muscle may increase the probability of developing future episodes of hyperammonemia, perpetuating the process. Direct effects of ammonia on specific brain centers such as the dorsomedial hypothalamus and reticular activating system may continue with global disruptions of cerebral metabolic-functional relationships to produce the protean manifestations of portal-systemic encephalopathy.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalJournal of Clinical Investigation
Volume78
Issue number1
StatePublished - Jan 1 1986
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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