Murine model to study brain, behavior and immunity during hepatic encephalopathy

Lindisley Ferreira Gomides, Pedro Elias Marques, Rafaela Vaz Pereira, Sylvia Stella Amaral, Thais Reis Lage, Gustavo Batista Menezes, Bruno Engler Faleiros, Fabiana Paiva Martins, Antonio Lúcio Teixeira, Gustavo Henrique Souza Resende, Patricia Alves Maia Guidine, Marco Antônio Peliky Fontes, Remo Castro Russo, Márcio Flávio Moraes, Giselle Foureaux, Anderson José Ferreira, Fabíola Mara Ribeiro, Mauro Martins Teixeira

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

AIM: 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 parameterswere 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalWorld Journal of Hepatology
Volume6
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Cerebral herniation
  • Hepatic encephalopathy
  • Intracranial hypertension
  • Liver injury
  • Neurological dysfunction
  • Neuropsychomotor abnormalities
  • Thioacetamide

ASJC Scopus subject areas

  • Hepatology

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