Jessica Heins1,2, Weinlei Jiang2, Sven Gottschalk2, Dieter Leibfritz1, Roger F. Butterworth2, Claudia Zwingmann1,2
1Department of Organic Chemistry, University of Bremen, Bremen, Germany; 2Centre de Recherche, Hospital Saint-Luc, Montreal, Quebec, Canada
Hyperammonemia is a key factor leading to neurological dysfunction in acute hepatic encephalopathy (HE). Recent evidence suggests a limited capacity of brain glutamine synthetase, the major detoxification mechanism for ammonia. Our aim was to determine in rats with HE whether prevention of ammonia-induced NMDA receptor overactivation is related to increased glutamine synthesis and attenuation of encephalopathy. 1H-, and 13C-NMR was used to measure brain metabolites following administration of [U-13C]glucose to rats with end-to-side portacaval anastomosis followed by hepatic artery ligation. The data demonstrate that memantine delays the time to coma, decreased blood ammonia and improves cerebral glutamine synthesis in HE.