Changes in brain metabolism during hyperammonemia and acute liver failure: results of a comparative 1H-NMR spectroscopy and biochemical investigation.
The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease-treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators. In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease-treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats. These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative.
Bosman
D K
DK
Laboratory of Experimental Medicine, University of Amsterdam, The Netherlands.
Deutz
N E
NE
De Graaf
A A
AA
vd Hulst
R W
RW
Van Eijk
H M
HM
Bovée
W M
WM
Maas
M A
MA
Jörning
G G
GG
Chamuleau
R A
RA
D000208:Acute Disease; D000641:Ammonia / Q000097:blood* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001927:Brain Diseases / Q000209:etiology; D004569:Electroencephalography; D005971:Glutamates / Q000097:blood / Q000378:metabolism; D018698:Glutamic Acid; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008102:Liver Circulation; D008107:Liver Diseases / Q000097:blood / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D011522:Protons; D051381:Rats; D011919:Rats, Inbred Strains; D014510:Urease / Q000494:pharmacology
D005971:Glutamates; D007773:Lactates; D011522:Protons; D008717:Methionine Sulfoximine; D019344:Lactic Acid; D018698:Glutamic Acid; D000641:Ammonia; D014510:Urease