title: Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis.
abstract: 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.
authors.affiliation: Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain. jover_rod@gva.es
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Regina
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Vicente
authors.initials: V
authors.lastname: Felipo
authors.forename: Ricardo
authors.initials: R
authors.lastname: Insausti
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
authors.forename: M Salud
authors.initials: MS
authors.lastname: García-Ayllón
authors.forename: Isabel
authors.initials: I
authors.lastname: Suárez
authors.forename: Asunción
authors.initials: A
authors.lastname: Candela
authors.forename: Antonio
authors.initials: A
authors.lastname: Compañ
authors.forename: Angel
authors.initials: A
authors.lastname: Esteban
authors.forename: Omar
authors.initials: O
authors.lastname: Cauli
authors.forename: Eva
authors.initials: E
authors.lastname: Ausó
authors.forename: Erika
authors.initials: E
authors.lastname: Rodríguez
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Eva
authors.initials: E
authors.lastname: Girona
authors.forename: Slaven
authors.initials: S
authors.lastname: Erceg
authors.forename: Pere
authors.initials: P
authors.lastname: Berbel
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Mateo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001652:Bile Ducts / Q000503:physiopathology; D001929:Brain Edema / Q000473:pathology* / Q000503:physiopathology; D004032:Diet; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000473:pathology* / Q000503:physiopathology; D022124:Hyperammonemia / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000032:analysis*; D008026:Ligation; D008106:Liver Cirrhosis, Experimental / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D018709:Statistics, Nonparametric
chemical_list: D018836:Inflammation Mediators