Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study

Donatello Carrino, Jacopo Junio Valerio Branca, Matteo Becatti, Ferdinando Paternostro, Gabriele Morucci, Massimo Gulisano, Lorenzo Di Cesare Mannelli and Alessandra Pacini
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Donatello Carrino: Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy
Jacopo Junio Valerio Branca: Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy
Matteo Becatti: Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Firenze, 50134 Firenze, Italy
Ferdinando Paternostro: Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy
Gabriele Morucci: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
Massimo Gulisano: Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy
Lorenzo Di Cesare Mannelli: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Firenze, 50139 Firenze, Italy
Alessandra Pacini: Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy

IJERPH, 2021, vol. 18, issue 5, 1-14

Abstract: 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.

Keywords: alcoholism; alcohol abuse; oxidative stress; blood–brain barrier; tight junction (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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