Brain monoamines in metabolic (endotoxic) coma a preliminary biochemical study in human postmortem material

Abstract

Spectrofluorometric assays of DA, 5-HT and 5-HIAA were performed in different areas of postmortem brains of humans who died in hepatic and uremic coma. Brain DA showed a mild general decrease, the average reduction being 20 to 30 percent of the controls. By contrast, 5-HT and 5-HIAA were markedly increased in most brain areas, most significantly in the reticular and raphé nuclei of the brainstem and in some parts of the limbic system. Despite individual and regional differences, the monoamine changes had similar patterns in both hepatic and uremic coma. These data in human brain which confirm previous clinical and experimental studies in hepatic encephalopathy suggest some common disorders of central monoamine metabolism in endotoxic coma of different origin. Brain edema, a constant feature in toxic coma, is probably due to increased 5-HT content in the brain, the pathophysiologic effect of 5-HT on the blood-brain barrier being well established. The prominent changes of indoleamine metabolism in the reticular brainstem and limbic systems may be related to disorders of consciousness.

Oral and Parenteral Nutrition with <i>L-</i><i>V</i>aline: Mode of Action

“…This could give rise to an increased concentra tion of serotonin and 5-hydroxyindole acetic acid in brain. In fact, such assumption has been confirmed recently in our laboratory with human autopsy material (16)(17)(18). The increased serotonin in brain may play a decisive role in the neurological sequelae of metabolic encephalopathy by changing neurotrans mission especially in the brain stem areas.…”

“…Previous biochemical studies have shown that this functional importance is reflected by excessive changes in concentrations of indoles in metabolic comata, while other brain regions do not show such profound changes (16,18). Postmortem time ranged from 3 to 10 h (mean: 7.6 t 3.1 h).…”

“…Raphe nuclei plus reticular formation were chosen, as they are part of the brainstem tegmentum, which has been shown to be involved in the natural control of consciousness (19) as discussed by Jellinger et al (16,18). Previous biochemical studies have shown that this functional importance is reflected by excessive changes in concentrations of indoles in metabolic comata, while other brain regions do not show such profound changes (16,18).…”

“…Spectrophotofluorometric assays of tryptophan, 5-hydroxytryptamine and 5-hydroxy indole acetic acid were performed in human postmortem brain material (raphe plus reticular formation) from 16 controls (9 males, 7 females; age 66 ± 4.2 years) who died of cardiac infarction, cardiovascular failures or bronchopneumonia and 8 individuals (4 males, 4 females: age 64.5 ± 2.8 years) who died of acute grade III or IV hepatic coma (see 16,22) due to alcoholic or postnecrotic liver cirrhosis, 3 of them with portocaval shunts with serum ammonia levels ranging from 173 to 352 /*g/100 ml (mean 268.3 t 25.5 jig/100 ml). These patients received partial parenteral treatment with commercial standard solutions, but none of them received parenteral administration of ¿-valine.…”

“…The peripheral and central tryptophan metabolism is disturbed in hepatic coma (16,18,28,30). The rate of production of cerebral serotonin is dependent upon the supply of tryptophan from the periphery and the rate of delivery of tryptophan depends upon its concentration in the plasma (7) as well as from other competing amino acids.…”