Mild swelling of astrocytes is proposed as the key event in the pathogenesis of HE (e.g., Takahashi et al. 1991). In cirrhosis, elevated blood level of ammonia is thought to result in elevated brain ammonia, which can be toxic (Weissenborn et al. 2007). It often has been proposed that the brain’s response to elevated ammonia levels is to combine ammonia and glutamate to make glutamine using glutamine synthetase, found primarily in astrocytes (Yamamoto et al. 1987). Thus, brain swelling in cirrhosis is thought to reflect an increase in astrocytic glutamine formation. The decrease in mI is thought to be a compensatory mechanism to counterbalance the osmotic effect of cerebral glutamine accumulation (Balata et al. 2003; Mardini et al. 2011). Although some articles claim to measure in vivo glutamine (e.g., Binesh et al. 2006; Chavarria et al. 2013; Jain et al. 2013; Kreis et al. 1992; McConnell et al. 1995), it is unlikely that the MRS method used in these cases permitted the separate detection of glutamate and glutamine, which are strongly coupled and difficult to detect independently, even with very
