THE EFFECTS OF AMMONIA AND PORTAL-SYSTEMIC SHUNTING ON BRAIN METABOLISM, NEUROTRANSMISSION AND INTRACRANIAL HYPERTENSION IN HYPERAMMONEMIA-INDUCED ENCEPHALOPATHY

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.