Main target of minimal hepatic encephalopathy: Morphophysiological, inflammatory and metabolic view

被引:11
作者
Arias, Natalia [1 ,2 ,3 ]
Mendez, Marta [2 ,3 ]
Gomez-Lazaro, Eneritz [4 ]
Azpiroz, Arantxa [4 ]
Arias, Jorge L. [2 ,3 ]
机构
[1] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England
[2] Univ Oviedo, Dept Psicol, Lab Neurociencias, Oviedo 33003, Spain
[3] Inst Neurociencias Principado Asturias, INEUROPA, Oviedo 33003, Spain
[4] Univ Basque Country, Dept Basic Psychol Proc & Their Dev, San Sebastian 20018, Spain
关键词
Minimal hepatic encephalopathy; Stimulus-response task; Cytochrome c-oxidase; Inflammation; GFAP-IR; Nucleator; Striatum; FIBRILLARY ACIDIC PROTEIN; WATER MAZE; DORSAL STRIATUM; DORSOLATERAL STRIATUM; EXPERIMENTAL-MODELS; MEMORY-SYSTEMS; SPATIAL MEMORY; LIVER-FAILURE; AMYGDALA; BRAIN;
D O I
10.1016/j.physbeh.2015.06.019
中图分类号
B84 [心理学];
学科分类号
04 ; 0402 ;
摘要
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 CO. activity in the ventral striatum. The PH group showed lower density of GFAP-IR and an increase in the tumour necrotic factor-alpha (TNF-alpha). 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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:247 / 254
页数:8
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