title: Rat CCl(4)-induced cirrhosis plus total portal vein ligation: a new model for the study of hyperammonaemia and brain oedema.
abstract: BACKGROUND
  Animal models used to study hyperammonaemic disorders related to chronic liver disease are unsatisfactory. These animals only develop hyperammonaemia and brain oedema when fed with diets supplemented with amonium acetate.
  
  
  OBJECTIVE
  To develop a novel experimental model of hyperammonaemia and brain oedema in CCl(4)-induced cirrhosis in rats.
  
  
  METHODS
  Four groups were studied: rats with sham intervention (S), rats with total portal vein ligation (TPVL), cirrhotic rats (LC), and cirrhotic rats with TPVL (LC+TPVL). When ascites was diagnosed, oral glutamine challenge (OGC) test was performed. Blood, liver, lungs and brain samples were collected to quantify liver function parameters, plasmatic and cerebral ammonia, endotoxaemia, liver and brain histology, brain oedema and portosystemic shunting degree.
  
  
  RESULTS
  LC+TPVL rats showed a significant increase in portosystemic shunting when compared with LC group and a significant derangement in liver function when compared with TPVL group. These alterations resulted in a significant increase in plasmatic and brain ammonia concentrations and a higher plasmatic endotoxaemia as compared with others. Similarly, the area under OGC curve was significantly increased in LC+TPVL group as compared with the others, and correlates with portal shunting. Low-grade brain oedema was only observed in LC+TPVL group. All cirrhotic groups showed liver regeneration nodules and type-II Alzheimer astrocytes
  
  
  CONCLUSIONS
  LC+TPVL reproduce the main alterations - portosystemic shunting, plasmatic and cerebral hyperammonaemia and low-grade brain oedema - observed in cirrhotic patients with hepatic encephalopathy.
authors.affiliation: Germans Trias i Pujol Health Science Research Institute, Badalona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Miquel
authors.forename: Ramon
authors.initials: R
authors.lastname: Bartolí
authors.forename: Gemma
authors.initials: G
authors.lastname: Odena
authors.forename: Anna
authors.initials: A
authors.lastname: Serafín
authors.forename: Eduard
authors.initials: E
authors.lastname: Cabré
authors.forename: Amparo
authors.initials: A
authors.lastname: Galan
authors.forename: Ignasi
authors.initials: I
authors.lastname: Barba
authors.forename: Joan
authors.initials: J
authors.lastname: Córdoba
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
mesh_terms: D000818:Animals; D001201:Ascites / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001929:Brain Edema / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002251:Carbon Tetrachloride; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000209:etiology; D006501:Hepatic Encephalopathy / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D022124:Hyperammonemia / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011168:Portal System / Q000503:physiopathology; D011169:Portal Vein / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002251:Carbon Tetrachloride