{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:23:56Z","timestamp":1791685436809,"version":"4.3.4"},"reference-count":124,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"#NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)\u2014a multiscale integrated approach to the study of the nervous system in health and disease","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]},{"name":"#NEXTGENERATIONEU (NGEU) and funded by the Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP), project MNESYS (PE0000006)\u2014a multiscale integrated approach to the study of the nervous system in health and disease","award":["CVU121216"],"award-info":[{"award-number":["CVU121216"]}]},{"name":"European Commission\u2019s FESR FSE 2014\u20132020 and POR CALABRIA FESR AZIONE 1.5.1 \u201cSupport for research infrastructures considered critical\/crucial for regional systems\u201d Nuova Piattaforma di Farmacologia Integrata e Tecnologie Avanzate. R.B.R. has been supported by the National Council of Science and Technology (CONACYT)","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}]},{"name":"European Commission\u2019s FESR FSE 2014\u20132020 and POR CALABRIA FESR AZIONE 1.5.1 \u201cSupport for research infrastructures considered critical\/crucial for regional systems\u201d Nuova Piattaforma di Farmacologia Integrata e Tecnologie Avanzate. R.B.R. has been supported by the National Council of Science and Technology (CONACYT)","award":["CVU121216"],"award-info":[{"award-number":["CVU121216"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma. Herein, we review the role of eNOS in both the regulation of cerebral blood flow and of synaptic plasticity and discuss the mechanisms by which cerebrovascular endothelial cells may transduce synaptic inputs into a NO signal. We further suggest that eNOS could play a critical role in vascular-to-neuronal communication by integrating signals converging onto cerebrovascular endothelial cells from both the streaming blood and active neurons.<\/jats:p>","DOI":"10.3390\/ijms25169071","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-6146","authenticated-orcid":false,"given":"Giorgia","family":"Scarpellino","sequence":"first","affiliation":[{"name":"Laboratory of General Physiology, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Laboratory of General Physiology, Department of Biology and Biotechnology \u201cL. Spallanzani\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4884-0925","authenticated-orcid":false,"given":"Roberto","family":"Berra-Romani","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, School of Medicine, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-6579","authenticated-orcid":false,"given":"Giovambattista","family":"De Sarro","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-962X","authenticated-orcid":false,"given":"Germano","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cV. Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7728-6815","authenticated-orcid":false,"given":"Teresa","family":"Soda","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Magna Graecia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0010-0098","authenticated-orcid":false,"given":"Francesco","family":"Moccia","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Sciences \u201cV. Tiberio\u201d, University of Molise, 86100 Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/288373a0","article-title":"The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine","volume":"288","author":"Furchgott","year":"1980","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9265","DOI":"10.1073\/pnas.84.24.9265","article-title":"Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide","volume":"84","author":"Ignarro","year":"1987","journal-title":"Proc. Natl. Acad. Sci. 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