{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:25:57Z","timestamp":1789050357985,"version":"build-2803163510"},"reference-count":144,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP18K06498"],"award-info":[{"award-number":["JP18K06498"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP16K06988"],"award-info":[{"award-number":["JP16K06988"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Excessive intake of ethanol is associated with severe brain dysfunction, and the subsequent neurological and behavioral abnormalities are well-established social risks. Many research studies have addressed how ethanol induces neurological toxicity. However, the underlying mechanisms with which ethanol induces neurological toxicity are still obscure, perhaps due to the variety and complexity of these mechanisms. Epithelial cells are in direct contact with blood and can thus mediate ethanol neurotoxicity. Ethanol activates the endothelial cells of blood vessels, as well as lymphatic vessels, in a concentration-dependent manner. Among various signaling mediators, nitric oxide plays important roles in response to ethanol. Endothelial and inducible nitric oxide synthases (eNOS and iNOS) are upregulated and activated by ethanol and enhance neuroinflammation. On the other hand, angiogenesis and blood vessel remodeling are both affected by ethanol intake, altering blood supply and releasing angiocrine factors to regulate neuronal functions. Thus, ethanol directly acts on endothelial cells, yet the molecular target(s) on endothelial cells remain unknown. Previous studies on neurons and glial cells have validated the potential contribution of membrane lipids and some specific proteins as ethanol targets, which may also be the case in endothelial cells. Future studies, based on current knowledge, will allow for a greater understanding of the contribution and underlying mechanisms of endothelial cells in ethanol-induced neurological toxicity, protecting neurological health against ethanol toxicity.<\/jats:p>","DOI":"10.3390\/life12111882","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T02:28:58Z","timestamp":1668479338000},"page":"1882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Blood Vessels as a Key Mediator for Ethanol Toxicity: Implication for Neuronal Damage"],"prefix":"10.3390","volume":"12","author":[{"given":"Kei","family":"Nakayama","sequence":"first","affiliation":[{"name":"Laboratory of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-8737","authenticated-orcid":false,"given":"Hiroshi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11910-003-0035-8","article-title":"Cerebrovascular complications of alcohol and sympathomimetic drug abuse","volume":"3","author":"Bruno","year":"2003","journal-title":"Curr. 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