Natalia Arias1, Marta Méndez2, Ignacio Alcalde3, Almudena Íñigo-Portugués3, Jesús Merayo-Lloves3, Jaime Arias4, Jorge L Arias2. 1. Institute for Liver and Digestive Health, University College of London, Department of Medicine, Rowland Hill Street, London, UK; INEUROPA, Instituto de Neurociencias del Principado de Asturias, Spain. Electronic address: n.arias@ucl.ac.uk. 2. INEUROPA, Instituto de Neurociencias del Principado de Asturias, Spain; Laboratorio de Neurociencias, Departamento de Psicología, Universidad de Oviedo, Plaza Feijoo s/n, 33003 Oviedo, Spain. 3. Fundación de Investigación Oftalmológica (FIO), Instituto Oftalmológico Fernández-Vega, Avda. Dres Fernández-Vega, 34, 33012 Oviedo, Spain. 4. Surgery Department, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
Abstract
BACKGROUND & AIMS: Minimal hepatic encephalopathy (mHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments in mHE. We studied one of its precipitating factors, portal hypertension which is driving the inflammatory process behind mHE. The purpose was to describe an indirect diagnostic method able to detect the pathology at early stages based on the study of the vascularization and mast cells conjunctival hyperplasia as secondary inflammatory response associated to portal hypertension. Finally, we correlated the presence of histological changes in the eye in mHE with deficits in behavioral task acquisition. METHODS: Rats were trained on a stimulus-response task and a spatial working memory task using the Morris water maze. Two groups of animals were used: a SHAM (sham-operated) group (n=10) and a portal hypertension (HT) group (n=10). The triple portal vein ligation method was used to create an animal model of mHE. Latencies to reach the platform, number of glial fibrillary acidic protein-immunoreactive astrocytes (GFAP-IR), mast cell expression and presence/absence of blood and lymphatic vessels were examined. RESULTS: There were differences in stimulus-response behavioral performance, with a deficit in the acquisition in the HT group. However, no differences between groups were found on the spatial working memory task. At the same time, differences between groups were found in the GFAP-IR density, which was lower in the HT group, and in the number of mast cells and the presence of vessels, which were higher in the HT group. CONCLUSIONS: In this study, we provide the first preliminary insight into the validity of exploring the eye as a possible tool to assess the diagnosis of mHE conditions.
BACKGROUND & AIMS: Minimal hepatic encephalopathy (mHE) has been shown to affect daily functioning, quality of life, driving and overall mortality. However, little is known about treating or diagnosing early impairments in mHE. We studied one of its precipitating factors, portal hypertension which is driving the inflammatory process behind mHE. The purpose was to describe an indirect diagnostic method able to detect the pathology at early stages based on the study of the vascularization and mast cells conjunctival hyperplasia as secondary inflammatory response associated to portal hypertension. Finally, we correlated the presence of histological changes in the eye in mHE with deficits in behavioral task acquisition. METHODS:Rats were trained on a stimulus-response task and a spatial working memory task using the Morris water maze. Two groups of animals were used: a SHAM (sham-operated) group (n=10) and a portal hypertension (HT) group (n=10). The triple portal vein ligation method was used to create an animal model of mHE. Latencies to reach the platform, number of glial fibrillary acidic protein-immunoreactive astrocytes (GFAP-IR), mast cell expression and presence/absence of blood and lymphatic vessels were examined. RESULTS: There were differences in stimulus-response behavioral performance, with a deficit in the acquisition in the HT group. However, no differences between groups were found on the spatial working memory task. At the same time, differences between groups were found in the GFAP-IR density, which was lower in the HT group, and in the number of mast cells and the presence of vessels, which were higher in the HT group. CONCLUSIONS: In this study, we provide the first preliminary insight into the validity of exploring the eye as a possible tool to assess the diagnosis of mHE conditions.