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Inflammasome activation has recently been implicated as a driver of myelin injury in multiple sclerosis (\n                    <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                    ) and its animal models, although the regulation and contributions of inflammasome activation in the demyelinated central nervous system (\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    ) are not completely understood. Herein, we investigated the\n                    <jats:styled-content style=\"fixed-case\">NLRP3<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">NBD<\/jats:styled-content>\n                    \u2010,\n                    <jats:styled-content style=\"fixed-case\">LRR<\/jats:styled-content>\n                    \u2010 and pyrin domain\u2010containing protein 3) inflammasome and its endogenous regulator\n                    <jats:styled-content style=\"fixed-case\">microRNA<\/jats:styled-content>\n                    \u2010223\u20103p within the demyelinated\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    in both\n                    <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                    and an animal model of focal demyelination. We observed that\n                    <jats:styled-content style=\"fixed-case\">NLRP3<\/jats:styled-content>\n                    inflammasome components and\n                    <jats:styled-content style=\"fixed-case\">microRNA<\/jats:styled-content>\n                    \u2010223\u20103p were upregulated at sites of myelin injury within activated macrophages and microglia. Both\n                    <jats:styled-content style=\"fixed-case\">microRNA<\/jats:styled-content>\n                    \u2010223\u20103p and a small\u2010molecule\n                    <jats:styled-content style=\"fixed-case\">NLRP3<\/jats:styled-content>\n                    inhibitor,\n                    <jats:styled-content style=\"fixed-case\">MCC950<\/jats:styled-content>\n                    , suppressed inflammasome activation in macrophages and microglia in vitro; compared with microglia, macrophages were more prone to inflammasome activation in vitro. Finally, systemic delivery of\n                    <jats:styled-content style=\"fixed-case\">MCC950<\/jats:styled-content>\n                    to mice following lysolecithin\u2010induced demyelination resulted in a significant reduction in axonal injury within demyelinated lesions. In conclusion, we demonstrate that\n                    <jats:styled-content style=\"fixed-case\">NLRP3<\/jats:styled-content>\n                    inflammasome activity by macrophages and microglia is a critical component of the inflammatory microenvironment following demyelination and represents a potential therapeutic target for inflammatory\u2010mediated demyelinating diseases, including\n                    <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\n                    .\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15650-fig-0010-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>\n                    Cover Image for this issue:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15422\">https:\/\/doi.org\/10.1111\/jnc.15422<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15650","type":"journal-article","created":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T11:24:35Z","timestamp":1653737075000},"page":"94-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Investigating the\n                    <scp>NLRP3<\/scp>\n                    inflammasome and its regulator\n                    <scp>miR<\/scp>\n                    \u2010223\u20103p in multiple sclerosis and experimental demyelination"],"prefix":"10.1111","volume":"163","author":[{"given":"Dylan A.","family":"Galloway","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Carew","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie N.","family":"Blandford","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochelle\u00a0Y.","family":"Benoit","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neva J.","family":"Fudge","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangyne","family":"Berry","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Division of Biomedical Sciences Memorial University of Newfoundland  St. John's Newfoundland and Labrador Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R. 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