THE EFFECTS OF AMMONIA AND PORTAL-SYSTEMIC SHUNTING ON BRAIN METABOLISM, NEUROTRANSMISSION AND INTRACRANIAL HYPERTENSION IN HYPERAMMONEMIA-INDUCED ENCEPHALOPATHY
Bapm. Vogels et al., THE EFFECTS OF AMMONIA AND PORTAL-SYSTEMIC SHUNTING ON BRAIN METABOLISM, NEUROTRANSMISSION AND INTRACRANIAL HYPERTENSION IN HYPERAMMONEMIA-INDUCED ENCEPHALOPATHY, Journal of hepatology, 26(2), 1997, pp. 387-395
Background/Aims: The pathogenetic factors contributing to encephalopat
hy in portacaval shunted rats with hyperammonaemia were studied. Metho
ds: Hyperammonaemia was induced by ammonium-acetate infusions in porta
caval shunted rats (2.8 mmol . kg bw(-1). h(-1); AI-portacaval shunted
rats) and in sham-portacaval shunted rats (6.5 mmol . kg bw(-1). h(-1
); AI-NORM rats). Severity of encephalopathy was quantified by clinica
l grading and EEG spectral analysis. Changes in brain metabolites were
assessed by amino acid analysis of brain cortex homogenates, whereas
changes in amino acids with neurotransmitter activity were assessed in
cerebrospinal fluid; brain water content was measured by subtracting
dry from wet brain weights and intracranial pressure was measured by a
pressure transducer connected to a cisterna magna cannula. Results: A
lthough similar increased blood and brain ammonia concentrations were
obtained in both experimental groups, only AI-portacaval shunted rats
developed encephalopathy, associated with a significant increase in in
tracranial pressure. Other significant differences were: higher concen
trations of brain glutamine and aromatic amino acids, higher concentra
tions of cerebrospinal fluid glutamine, aromatic amino acids, glutamat
e and aspartate in AI-portacaval shunted rats than in AI-NORM rats. Co
nclusions: These results indicate that hyperammonaemia alone does not
induce encephalopathy, whereas portal-systemic shunting adds an essent
ial contribution to the pathogenesis of encephalopathy. It is hypothes
ised that the larger increase in brain glutamine in AI-portacaval shun
ted rats than in AI-NORM rats is responsible for increased brain conce
ntrations of aromatic amino acids, for cell swelling and for extracell
ular release of glutamate and aspartate. This might promote encephalop
athy. If cell swelling is not restricted, intracranial hypertension wi
ll develop.