Hyperammonaemia depresses glucose consumption throughout the brain

Abstract

1. Recent studies showed that hyperammonaemia caused many of the metabolic changes in portacaval-shunted rats, a model of hepatic encephalopathy. These changes included a depression in the cerebral metabolic rate of glucose (CMR(Glc)), an indication of decreased brain function. 2. The purpose of the present experiments was to determine whether the depression of CMR(Glc) caused by ammonia is confined to certain brain structures, or whether the depression is an overall decrease in all structures, such as occurs in portacaval-shunted rats. To accomplish this objective, rats were made hyperammonaemic by giving them intraperitoneal injections of 40 units of urease/kg body wt. every 12 h; control rats received 0.154 M-NaCl. CMR(Glc) was measured 48 h after the first injection, by using quantitative autoradiography with [6-(l4)C]glucose as a tracer. 3. The experimental rats had high plasma ammonia concentrations (control 70 nmol/ml, experimental 610 nmol/ml) and brain glutamine levels (control 5.4 μmol/ml, experimental 19.5 μmol/ml). Hyperammonaemia decreased CMR(Glc) throughout the brain by an average of 19 %. CMR(Glc) showed an inverse correlation with plasma ammonia, but a stronger correlation with the brain glutamine content. 4. Hyperammonaemia led to a decrease in CMR(Glc) throughout the brain that was indistinguishable from the pattern seen in portacaval-shunted rats. This is taken as further evidence that the cerebral depression found in portacaval-shunted rats is a consequence of hyperammonaemia. The observation that depression of CMR(Glc) correlated more closely with brain glutamine content than with plasma ammonia suggests that metabolism of ammonia is an important step in the pathological sequence.