title: Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy.
abstract: Hepatic encephalopathy has traditionally been considered a reversible disorder. However, recent studies suggested that repeated episodes of hepatic encephalopathy cause persistent impairment leading to neuronal loss. The aims of our study were the development of a new animal model that reproduces the course of episodic hepatic encephalopathy and the identification of neurodegeneration evidences. Rats with portacaval anastomosis underwent simulated episodes of hepatic encephalopathy, triggered by the regular administration of ammonium acetate, and/or lipopolysaccharide. The neurological status was assessed and neuronal loss stereologically quantified in motor areas. During the simulated episodes, ammonia induced reversible motor impairment in portacaval anastomosis rats. In cerebellum, stereology showed a reduction in Purkinje cell population in portacaval anastomosis and PCA+NH3groups and morphological changes. An increase in astrocyte size in PCA+NH3group and activated microglia in groups treated with ammonium acetate and/or lipopolysaccharide was observed. A modulation of neurodegeneration-related genes and the presence of apoptosis in Bergmann glia were observed. This new animal model reproduces the clinical course of episodic hepatic encephalopathy when ammonia is the precipitant factor and demonstrates the existence of neuronal loss in cerebellum. The persistence of over-activated microglia and reactive astrocytes could participate in the apoptosis of Bergmann glia and therefore Purkinje cell degeneration.
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.|3 Departament Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: García-Lezana
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.|3 Departament Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.|4 Center for Fetal, Cellular and Mollecular Therapy, Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center (CCHMC), OH, US.
authors.forename: Marc
authors.initials: M
authors.lastname: Oria
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Romero-Giménez
authors.affiliation: 5 Neurodegenerative Diseases Research Group, Institut de Recerca Valld'Hebron (VHIR) - Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bové
authors.affiliation: 5 Neurodegenerative Diseases Research Group, Institut de Recerca Valld'Hebron (VHIR) - Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Barcelona, Spain.|6 Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain.|7 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Vila
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.|3 Departament Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Genescà
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.|3 Departament Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Chavarria
authors.affiliation: 1 Liver Unit, Institut de Recerca Valld'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Barcelona, Spain.|2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.|3 Departament Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cordoba
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000473:pathology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D017628:Microglia / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D011689:Purkinje Cells / Q000473:pathology; D051381:Rats
chemical_list: D000085:Acetates; D008070:Lipopolysaccharides; C018824:ammonium acetate
keywords: Apoptosis; astrocytes; inflammation; microglia; neurodegeneration