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Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study
In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Fu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967408/ https://www.ncbi.nlm.nih.gov/pubmed/33799986 http://dx.doi.org/10.3390/ijerph18052683 |
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author | Carrino, Donatello Branca, Jacopo Junio Valerio Becatti, Matteo Paternostro, Ferdinando Morucci, Gabriele Gulisano, Massimo Di Cesare Mannelli, Lorenzo Pacini, Alessandra |
author_facet | Carrino, Donatello Branca, Jacopo Junio Valerio Becatti, Matteo Paternostro, Ferdinando Morucci, Gabriele Gulisano, Massimo Di Cesare Mannelli, Lorenzo Pacini, Alessandra |
author_sort | Carrino, Donatello |
collection | PubMed |
description | In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood–brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10–1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood–brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol. |
format | Online Article Text |
id | pubmed-7967408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79674082021-03-18 Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study Carrino, Donatello Branca, Jacopo Junio Valerio Becatti, Matteo Paternostro, Ferdinando Morucci, Gabriele Gulisano, Massimo Di Cesare Mannelli, Lorenzo Pacini, Alessandra Int J Environ Res Public Health Article In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood–brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10–1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood–brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol. MDPI 2021-03-07 /pmc/articles/PMC7967408/ /pubmed/33799986 http://dx.doi.org/10.3390/ijerph18052683 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Carrino, Donatello Branca, Jacopo Junio Valerio Becatti, Matteo Paternostro, Ferdinando Morucci, Gabriele Gulisano, Massimo Di Cesare Mannelli, Lorenzo Pacini, Alessandra Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title | Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title_full | Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title_fullStr | Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title_full_unstemmed | Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title_short | Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study |
title_sort | alcohol-induced blood-brain barrier impairment: an in vitro study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967408/ https://www.ncbi.nlm.nih.gov/pubmed/33799986 http://dx.doi.org/10.3390/ijerph18052683 |
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