title: Main target of minimal hepatic encephalopathy: Morphophysiological, inflammatory and metabolic view.
abstract: Although often not considered clinically relevant and, therefore, not diagnosed or treated, minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. To discover early impairments involved in MHE, we studied one of its precipitating factors, portal hypertension. Rats were trained on a stimulus-response task using the Morris water maze. Two groups of animals were used: a SHAM (sham-operated) group (n= 13) and a portal hypertension (PH) group (n= 13). The triple portal vein ligation method was used to create an animal model of an early developmental phase of HE. Brain metabolic activity was studied with cytochrome c-oxidase histochemistry (C.O.). Neuronal nuclear volume was assessed by nucleator probe; the number of glial fibrillary acidic protein-immunoreactive astrocytes (GFAP-IR) and proinflammatory mediators was measured. The results revealed that the PH group was not able to reach the behavioural criterion, in contrast to the SHAM group. The metabolic brain consumption revealed decreased C.O. activity in the ventral striatum. The PH group showed lower density of GFAP-IR and an increase in the tumour necrotic factor-α (TNF-α). The PH group showed decreased neuronal nuclear volume in the dorsal striatum. On the contrary, increased neuronal nuclear volume was found in the ventral striatum. For the first time, a relationship has been established between inflammation, astrocytic and neural damage, and brain metabolic impairment in a model of MHE. Disruption of the striatum and related structures was highlighted as the main target in early stages of HE. Finally, a simple task was presented to assess the subtle impairments found in the clinic, which could provide fresh insights into the development of new tools for the assessment of MHE.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK; INEUROPA, Instituto de Neurociencias del Principado de Asturias, Plaza Feijoo s/n., 33003 Oviedo, Spain. Electronic address: na423@cam.ac.uk.
authors.forename: Natalia
authors.initials: N
authors.lastname: Arias
authors.affiliation: Laboratorio de Neurociencias, Departamento de Psicología, Universidad de Oviedo, Plaza Feijoo s/n., 33003 Oviedo, Spain; INEUROPA, Instituto de Neurociencias del Principado de Asturias, Plaza Feijoo s/n., 33003 Oviedo, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Méndez
authors.affiliation: Department of Basic Psychological Processes and their Development, Basque Country University, Avda, Tolosa 70, 20018 San Sebastian, Spain.
authors.forename: Eneritz
authors.initials: E
authors.lastname: Gómez-Lázaro
authors.affiliation: Department of Basic Psychological Processes and their Development, Basque Country University, Avda, Tolosa 70, 20018 San Sebastian, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Azpiroz
authors.affiliation: Laboratorio de Neurociencias, Departamento de Psicología, Universidad de Oviedo, Plaza Feijoo s/n., 33003 Oviedo, Spain; INEUROPA, Instituto de Neurociencias del Principado de Asturias, Plaza Feijoo s/n., 33003 Oviedo, Spain.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Arias
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D053145:Cell Nucleus Size; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006975:Hypertension, Portal / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure*; D009929:Organ Size / Q000502:physiology; D011169:Portal Vein / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D013154:Spleen / Q000473:pathology
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D003576:Electron Transport Complex IV
keywords: Cytochrome c-oxidase; GFAP-IR; Inflammation; Minimal hepatic encephalopathy; Nucleator; Stimulus–response task; Striatum