title: 1H and31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism.
abstract: Chronic liver disease (CLD) leads to a spectrum of neuropsychiatric disorders named hepatic encephalopathy (HE). Even though brain energy metabolism is believed to be altered in chronic HE, few studies have explored energy metabolism in CLD-induced HE, and their findings were inconsistent. The aim of this study was to characterize for the first time in vivo and longitudinally brain metabolic changes in a rat model of CLD-induced HE with a focus on energy metabolism, using the methodological advantages of high field proton and phosphorus Magnetic Resonance Spectroscopy (1H- and31P-MRS). Wistar rats were bile duct ligated (BDL) and studied before BDL and at post-operative weeks 4 and 8. Glutamine increased linearly over time (+146 %) together with plasma ammonium (+159 %). As a compensatory effect, other brain osmolytes decreased: myo-inositol (-36 %), followed by total choline and creatine. A decrease in the neurotransmitters glutamate (-17 %) and aspartate (-28 %) was measured only at week 8, while no significant changes were observed for lactate and phosphocreatine. Among the other energy metabolites measured by31P-MRS, we observed a non-significant decrease in ATP together with a significant decrease in ADP (-28 %), but only at week 8 after ligation. Finally, brain glutamine showed the strongest correlations with changes in other brain metabolites, indicating its importance in type C HE. In conclusion, mild alterations in some metabolites involved in energy metabolism were observed but only at the end stage of the disease when edema and neurological changes are already present. Therefore, our data indicate that impaired energy metabolism is not one of the major causes of early HE symptoms in the established model of type C HE.
authors.affiliation: Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Rackayova
authors.affiliation: Service of Biomedicine, University Hospital of Lausanne, Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Braissant
authors.affiliation: Swiss Center for Liver Disease in Children, Department of Pediatrics, University Hospitals Geneva, Geneva, Switzerland.
authors.forename: Valérie A
authors.initials: VA
authors.lastname: McLin
authors.affiliation: Centre d'Imagerie Biomedicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Corina
authors.initials: C
authors.lastname: Berset
authors.affiliation: Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Lanz
authors.affiliation: Centre d'Imagerie Biomedicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. cristina.cudalbu@epfl.ch.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cudalbu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology*; D006501:Hepatic Encephalopathy / Q000175:diagnosis* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D010761:Phosphorus Radioisotopes; D011522:Protons; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010761:Phosphorus Radioisotopes; D011522:Protons
keywords: Bile duct ligation; Energy metabolism; Phosphorus magnetic resonance spectroscopy; Proton magnetic resonance spectroscopy; Type C hepatic encephalopathy; in vivo