Cerebellar neurodegeneration in a new rat model of episodic hepatic encephalopathy

Teresa García-Lezana, Marc Oria, Jordi Romero-Giménez, Jordi Bové, Miquel Vila, Joan Genescà, Laia Chavarria, Juan Cordoba

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12 Citations (Scopus)


© The Author(s) 2016. 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+NH 3 groups and morphological changes. An increase in astrocyte size in PCA+NH 3 group 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.
Original languageEnglish
Pages (from-to)927-937
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number3
Publication statusPublished - 1 Mar 2017


  • Apoptosis
  • astrocytes
  • inflammation
  • microglia
  • neurodegeneration


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