Brain Energy Metabolism in Chronic Hepatic Encephalopathy: an in vivo and longitudinal Magnetic Resonance Spectroscopy study on a rat model of Biliary Cirrhosis

• Autor(a) principal: Morais, André Rocha
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/103154
• topic: Hepatic Encephalopathy; chronic liver disease; hyperammonemia; ligation; osmoregulation; Glutamine Hypothesis; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Hepatic Encephalopathy is a major neuropsychiatric syndrome that arises from acute and chronic liver disease-induced cerebral disorders. Chronic hepatic encephalopathy is associated with cirrhosis and stems from progressive liver brosis, thereby inducing portal hypertension and deterioration in liver function. Hepatic encephalopathy is characterized by increased levels of ammonia, named hyperammonemia. Given that hepatic encephalopathy induces disturbances in cerebral osmoregulation, neurotransmission, antioxidant and energy metabolism, 1H magnetic resonance spectroscopy was performed longitudinally on a rat model of Type C chronic hepatic encephalopathy to assess cerebral osmolyte, energy, neurotransmitter and antioxidant metabolite concentrations. This technique was combined with 31P Magnetic resonance spectroscopy with the purpose of measuring additional energy metabolite concentrations. The studies were carried out at 9.4 Tesla. Rats undergone bile-duct ligation and studies were performed at several stages of disease progression: 0, 4, 6 and 8 weeks after surgery. Results regarding brain osmolyte concentration showed a signi cant increase in Gln, a decrease in tChol and Ins as well as trends of decrease in Tau and Cr. These results suggest an osmoregulatory response to the increase of Gln. In what concerns to neurotransmission, a decrease was observed in Asp and Glu suggesting that neurotransmission is a ected by hyperammonemia which may be an evidence of alterations in the out ow of Gln from astrocytes and interfere with Glu synthesis. The reduction of antioxidants Asc and GSH may indicate oxidative stress due to ammonia exposure. Small trends of decrease observed in -ATP and other energy metabolites which may be a sign of energy disturbances but not signi cant to cause brain oedema. Overall, an increase in concentration levels of Gln it is pointed as the main cause of the minimal brain oedema supported by Glutamine Hypothesis. The results of this study are encouraging and relevant for future studies.