Hyperammonaemia depresses glucose consumption throughout the brain.
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 (CMRGlc), an indication of decreased brain function. 2. The purpose of the present experiments was to determine whether the depression of CMRGlc 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. CMRGlc was measured 48 h after the first injection, by using quantitative autoradiography with [6-14C]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 mumol/ml). Hyperammonaemia decreased CMRGlc throughout the brain by an average of 19%. CMRGlc showed an inverse correlation with plasma ammonia, but a stronger correlation with the brain glutamine content. 4. Hyperammonaemia led to a decrease in CMRGlc 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 CMRGlc correlated more closely with brain glutamine content than with plasma ammonia suggests that metabolism of ammonia is an important step in the pathological sequence.
Jessy
J
J
Department of Physiology and Biophysics, Chicago Medical School, North Chicago, IL 60064.
DeJoseph
M R
MR
Hawkins
R A
RA
D000641:Ammonia / Q000097:blood*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D001931:Brain Mapping; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats
D001786:Blood Glucose; D000641:Ammonia; D005947:Glucose