{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:57:14Z","timestamp":1789873034642,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>In recent years, alcohol abuse has dramatically grown with deleterious consequence for people\u2019s 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\u2013brain 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\u20131713 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\u2013brain 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.<\/jats:p>","DOI":"10.3390\/ijerph18052683","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:20:43Z","timestamp":1615148443000},"page":"2683","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Donatello","family":"Carrino","sequence":"first","affiliation":[{"name":"Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3179-0706","authenticated-orcid":false,"given":"Jacopo Junio Valerio","family":"Branca","sequence":"additional","affiliation":[{"name":"Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-5908","authenticated-orcid":false,"given":"Matteo","family":"Becatti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-3499","authenticated-orcid":false,"given":"Ferdinando","family":"Paternostro","sequence":"additional","affiliation":[{"name":"Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Morucci","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gulisano","sequence":"additional","affiliation":[{"name":"Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-4432","authenticated-orcid":false,"given":"Lorenzo","family":"Di Cesare Mannelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Firenze, 50139 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-7626","authenticated-orcid":false,"given":"Alessandra","family":"Pacini","sequence":"additional","affiliation":[{"name":"Department Experimental and Clinical Medicine, Anatomy and Histology Section, University of Firenze, 50134 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,7]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). 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