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We hypothesized that BK channel openers would be neuroprotective during neuroinflammatory, autoimmune disease. The neurodegenerative disease was induced in a mouse experimental autoimmune encephalomyelitis model with translational value to detect neuroprotection in multiple sclerosis. Following the treatment with the BK channel openers, BMS-204253 and VSN16R, neuroprotection was assessed using subjective and objective clinical outcomes and by quantitating spinal nerve content. Treatment with BMS-204253 and VSN16R did not inhibit the development of relapsing autoimmunity, consistent with minimal channel expression via immune cells, nor did it change leukocyte levels in rodents or humans. However, it inhibited the accumulation of nerve loss and disability as a consequence of autoimmunity. Therefore, in addition to symptom control, BK channel openers have the potential to save nerves from excitotoxic damage and could be useful as either stand-alone neuroprotective agents or as add-ons to current disease-modifying treatments that block relapsing MS but do not have any direct neuroprotective activity.<\/jats:p>","DOI":"10.3390\/ph16070972","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T02:37:29Z","timestamp":1688697449000},"page":"972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroprotection in an Experimental Model of Multiple Sclerosis via Opening of Big Conductance, Calcium-Activated Potassium Channels"],"prefix":"10.3390","volume":"16","author":[{"given":"Gareth","family":"Pryce","sequence":"first","affiliation":[{"name":"BartsMS, The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Sisay","sequence":"additional","affiliation":[{"name":"BartsMS, The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Giovannoni","sequence":"additional","affiliation":[{"name":"BartsMS, The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6817-5064","authenticated-orcid":false,"given":"David L.","family":"Selwood","sequence":"additional","affiliation":[{"name":"Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-8711","authenticated-orcid":false,"given":"David","family":"Baker","sequence":"additional","affiliation":[{"name":"BartsMS, The Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.13819","article-title":"Multiple sclerosis\u2014A review","volume":"26","author":"Dobson","year":"2019","journal-title":"Eur. 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