Brain edema and inflammatory activation in bile duct ligated rats with diet-induced hyperammonemia: A model of hepatic encephalopathy in cirrhosis.
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.
Jover
Rodrigo
R
Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain. jover_rod@gva.es
Rodrigo
Regina
R
Felipo
Vicente
V
Insausti
Ricardo
R
Sáez-Valero
Javier
J
García-Ayllón
M Salud
MS
Suárez
Isabel
I
Candela
Asunción
A
Compañ
Antonio
A
Esteban
Angel
A
Cauli
Omar
O
Ausó
Eva
E
Rodríguez
Erika
E
Gutiérrez
Ana
A
Girona
Eva
E
Erceg
Slaven
S
Berbel
Pere
P
Pérez-Mateo
Miguel
M
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
D018836:Inflammation Mediators