title: Murine model to study brain, behavior and immunity during hepatic encephalopathy.
abstract: OBJECTIVE
  To propose an alternative model of hepatic encephalopathy (HE) in mice, resembling the human features of the disease.
  
  
  METHODS
  Mice received two consecutive intraperitoneal injections of thioacetamide (TAA) at low dosage (300 mg/kg). Liver injury was assessed by serum transaminase levels (ALT) and liver histology (hematoxylin and eosin). Neutrophil infiltration was estimated by confocal liver intravital microscopy. Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time. Hemodynamic parameters were measured through tail cuff. Ammonia levels were quantified in serum and brain samples. Electroencephalography (EEG) and psychomotor activity score were performed to show brain function. Brain edema was evaluated using magnetic resonance imaging.
  
  
  RESULTS
  Mice submitted to the TAA regime developed massive liver injury, as shown by elevation of serum ALT levels and a high degree of liver necrosis. An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury. This led to mice mortality and weight loss, which was associated with severe coagulopathy. Furthermore, TAA-treated mice presented with increased serum and cerebral levels of ammonia, in parallel with alterations in EEG spectrum and discrete brain edema, as shown by magnetic resonance imaging. In agreement with this, neuropsychomotor abnormalities ensued 36 h after TAA, fulfilling several HE features observed in humans. In this context of liver injury and neurological dysfunction, we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome.
  
  
  CONCLUSIONS
  In summary, we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans, which may provide new insights for treatment.
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Lindisley Ferreira
authors.initials: LF
authors.lastname: Gomides
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Pedro Elias
authors.initials: PE
authors.lastname: Marques
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Bruno Engler
authors.initials: BE
authors.lastname: Faleiros
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Rafaela Vaz
authors.initials: RV
authors.lastname: Pereira
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Sylvia Stella
authors.initials: SS
authors.lastname: Amaral
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Thais Reis
authors.initials: TR
authors.lastname: Lage
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Gustavo Henrique Souza
authors.initials: GH
authors.lastname: Resende
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Patricia Alves Maia
authors.initials: PA
authors.lastname: Guidine
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Giselle
authors.initials: G
authors.lastname: Foureaux
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Fabíola Mara
authors.initials: FM
authors.lastname: Ribeiro
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Fabiana Paiva
authors.initials: FP
authors.lastname: Martins
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Marco Antônio Peliky
authors.initials: MA
authors.lastname: Fontes
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Anderson José
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Remo Castro
authors.initials: RC
authors.lastname: Russo
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Márcio Flávio
authors.initials: MF
authors.lastname: Moraes
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Antonio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Laboratório de Imunobiofotônica, Department of Morphology, ICB, UFMG, Belo Horizonte 31270-901, Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
keywords: Cerebral herniation; Hepatic encephalopathy; Intracranial hypertension; Liver injury; Neurological dysfunction; Neuropsychomotor abnormalities; Thioacetamide