Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis

Presented in part as a poster at 2005 Meeting EASL, Paris.
Studies of the pathogenesis of hepatic encephalopathy are hampered by the lack of a satisfactory animal model. We examined the neurological features of rats after bile duct ligation fed a hyperammonemic diet (BDL+HD). Six groups were studied: sham, sham pair-fed, hyperammonemic, bile duct ligation (BDL), BDL pair fed, and BDL+HD. The BDL+HD rats were made hyperammonemic via an ammonia-containing diet that began 2 weeks after operation. One week later, the animals were sacrificed. BDL+HD rats displayed an increased level of cerebral ammonia and neuroanatomical characteristics of hepatic encephalopathy (HE), including the presence of type II Alzheimer astrocytes. Both BDL and BDL+HD rats showed activation of the inflammatory system. BDL+HD rats showed an increased amount of brain glutamine, a decreased amount of brain myo-inositol, and a significant increase in the level of brain water. In coordination tests, BDL+HD rats showed severe impairment of motor activity and performance as opposed to BDL rats, whose results seemed only mildly affected. In conclusion, the BDL+HD rats displayed similar neuroanatomical and neurochemical characteristics to human HE in liver cirrhosis. Brain edema and inflammatory activation can be detected under these circumstances.
Supported by grants from Instituto de Salud Carlos III, Convocatoria de RedesTematicas (G03/155 and C03/02); Conselleria de Sanitat, Escuela Valenciana para Estudios de la Salud (BM-004/2002); Organisme Public Valencia d’Investigacio, Ajudes per a Accions Especials (21-2002), Generalitat Valenciana,GV Grupos 03/053, Junta de Comunidades de Castilla-La Mancha (GC-02-022)and Instituto de Salud Carlos III (PI03/0576).