Brain monoamines in human hepatic encephalopathy

Jellinger, K. A.; Riederer, Peter; Kleinberger, G; Wuketich, S; Kothbauer, P

doi:10.1007/bf00684999

Cited by 49 publications

(26 citation statements)

References 22 publications

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“…Administration of large doses of tryptophan to Eck-fistula dogs results in a neuropsychiatric syndrome resembling PSE (67). Furthermore, CSF and brain concentrations of tryptophan are increased in patients in hepatic coma (68,69). There is evidence to suggest that such changes are linked to ammonia accumulation in brain.…”

Section: Neuroactive Tryptophan Metabolites Serotonin (5-hydroxytrypmentioning

confidence: 97%

Current Theories on the Pathogenesis of Hepatic Encephalopathy

Mousseau

Butterworth

1994

Experimental Biology and Medicine

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Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of both acute and chronic liver disease. Several hypotheses have emerged following the development of appropriate animal models of HE and following studies using postmortem brain tissue from HE patients. It was originally suggested that primary energy failure was responsible for HE; however, there is now mounting evidence that the pathogenetic defect involves neurotransmission failure. Specific neurotransmitter systems implicated in the pathogenesis of portal-systemic encephalopathy (PSE) include the excitatory amino acid glutamate as well as neuroactive and/or neurotoxic biogenic amine metabolites. Although it has been proposed that alterations in the gamma-aminobutyric acid (GABA) system may play a pathogenic role in HE associated with both chronic and acute liver failure, there is now overwhelming evidence to the contrary. On the other hand, there is evidence to suggest that a subgroup of patients with HE have increased blood and CSF concentrations of substances that bind to GABA-related benzodiazepine receptors in brain. Alterations of both the glutamatergic and serotoninergic neurotransmitter systems in PSE likely result from the metabolic consequences of chronic exposure of brain to toxic levels of ammonia. In addition to its effects on glutamatergic and serotoninergic systems during chronic liver disease, ammonia has been intimately associated with the brain edema invariably observed in acute liver failure. It is evident that, regardless of the type of liver failure, effective reductions of ammonia levels remains the strategy of choice in the prevention of encephalopathy. The further elucidation of neurotransmitter alterations in HE could result in novel "downstream" neuropharmacologic approaches to its prevention and treatment.

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Section: Neuroactive Tryptophan Metabolites Serotonin (5-hydroxytrypmentioning

confidence: 97%

Current Theories on the Pathogenesis of Hepatic Encephalopathy

Mousseau

Butterworth

1994

Experimental Biology and Medicine

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“…The high levels of octopamine in these two patients could not be influenced by the infusion of the branched chain amino acid L-valine, although normalization of plasma amino acid patterns and improvement of hepatic encephalopathy could be dem- onstrated in dogs following infusion of amino acids rich in branched chain amino acids and low in aromatic amino acids (Fischer et al I975). Furthermore after treatment of patients with hepatic coma with L-valine postmortem levels of 5-hydroxyindole acetic acid and serotonin in the brain were found to be normal or even decreased compared to control, whereas elevated levels of 5-hydroxyindole acetic acid and serotonin were present in the brain of a comparable group of patients without L-valine infusion [14].…”

Section: Discussionmentioning

confidence: 80%

Plasma catecholamines in hepatic coma and liver cirrhosis: Role of octopamine

et al. 1981

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“…Therefore, the development of coma in experimental hyperammonemia and in experimental hepatic encephalopathy caused by a failing liver function may have different biochemical background, and the study casts doubt on the role of serotonin for the development of coma as a consequence of hyperammonemia, while some neurologic findings in HE may be referred to an altered brain serotonin metabolism as suggested by others [15,17,22,23].…”

Section: Discussionmentioning

confidence: 96%

“…This has been suggested to be the reason for the altered brain levels of the neurotransmitter serotonin (5-HT) demonstrable in patients with hepatic encephalopathy [23] and in experimental animals after portacaval shunt [1], hepatectomy [17], or liver devascularization [13]. The concentrations of norepinephrine (NE) in the brain are decreased after hepatectomy [18] and liver ischemia [14].…”

Section: Introductionmentioning

confidence: 99%

The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats

et al. 1989

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The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portocaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.

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Brain monoamines in human hepatic encephalopathy

Cited by 49 publications

References 22 publications

Current Theories on the Pathogenesis of Hepatic Encephalopathy

Current Theories on the Pathogenesis of Hepatic Encephalopathy

Plasma catecholamines in hepatic coma and liver cirrhosis: Role of octopamine

The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats

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