{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:18:22Z","timestamp":1790363902630,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:00:00Z","timestamp":1733616000000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072488"],"award-info":[{"award-number":["82072488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272549"],"award-info":[{"award-number":["82272549"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102620"],"award-info":[{"award-number":["82102620"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472498"],"award-info":[{"award-number":["82472498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472505"],"award-info":[{"award-number":["82472505"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The treatment of spinal cord injury (SCI) is usually ineffective, because neuroinflammatory secondary injury is an important cause of the continuous development of spinal cord injury, and microglial pyroptosis is an important step of neuroinflammation. Recently, Bmal1, a core component of circadian clock genes (CCGs), has been shown to play a regulatory role in various tissues and cells. However, it is still unclear whether Bmal1 regulates microglial pyroptosis after SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we established an in\u00a0vivo mouse model of SCI using Bmal1 knockout (KO) mice and wild\u2010type (WT) mice, and lipopolysaccharide (LPS)\u2010induced pyroptosis in BV2 cells as an in\u00a0vitro model. A series of molecular and histological methods were used to detect the level of pyroptosis and explore the regulatory mechanism in\u00a0vivo and in\u00a0vitro respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both in\u00a0vitro and in\u00a0vivo results showed that Bmal1 inhibited NLRP3 inflammasome activation and microglial pyroptosis after SCI. Further analysis showed that Bmal1 inhibited pyroptosis\u2010related proteins (NLRP3, Caspase\u20101, ASC, GSDMD\u2010N) and reduced the release of IL\u201018 and IL\u20101\u03b2 by inhibiting the NF\u2010\u03baB \/MMP9 pathway. It was important that NF\u2010\u03baB was identified as a transcription factor that promotes the expression of MMP9, which in turn regulates microglial pyroptosis after SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study initially identified that Bmal1 regulates the NF\u2010\u03baB \/MMP9 pathway to reduce microglial pyroptosis and thereby reduce secondary spinal cord injury, providing a new promising therapeutic target for SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70130","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T02:35:13Z","timestamp":1733711713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Circadian Clock Gene Bmal1 Regulates Microglial Pyroptosis After Spinal Cord Injury via\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>MMP9<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-4245","authenticated-orcid":false,"given":"Dachuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feizhou","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Huashan Hospital Fudan University  Shanghai 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