{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:45:33Z","timestamp":1792759533991,"version":"4.5.0"},"reference-count":66,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Zhejiang Provincial Clinical Key Specialty Construction Program - Department of Emergency Medicine","award":["2025-ZJZK-001"],"award-info":[{"award-number":["2025-ZJZK-001"]}]},{"name":"Jiaxing Health Science and Technology Plan Project","award":["No. JWKJ-25003"],"award-info":[{"award-number":["No. JWKJ-25003"]}]},{"name":"Key Research and Development Program of Zhejiang Province","award":["2024C3186"],"award-info":[{"award-number":["2024C3186"]}]},{"name":"the Jiaxing Key Discipline Project","award":["No. 2023-ZC-004"],"award-info":[{"award-number":["No. 2023-ZC-004"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) induces severe secondary injury where molecular mechanisms remain unclear. This study investigates the involvement of the cyclic GMP-AMP synthase\u2013stimulator of interferon genes (cGAS-STING) signaling pathway in this process and evaluates the neuroprotective effect of the L-type calcium channel blocker nimodipine, focusing on calcium homeostasis, mitochondrial function, and inflammatory signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Using primary neuronal and mouse TBI models, we assessed outcomes\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      fluorescent calcium imaging, JC-1 staining, Western blot, quantitative PCR (qPCR)\/reverse transcription\u2013quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and behavioral tests. Nimodipine was applied to inhibit L-type channels, specifically testing its role in reducing mitochondrial DNA (mtDNA) release, blocking cGAS-STING activation, and suppressing neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      TBI markedly activated the cGAS-STING pathway, increasing pro-inflammatory factors and apoptosis. In the cellular oxygen\u2013glucose deprivation model, calcium overload was directly observed by Fluo-4 AM staining and was associated with subsequent mitochondrial permeability transition pore opening and mtDNA release, identifying this process as a key upstream event for cGAS-STING activation. Nimodipine inhibited intracellular calcium overload, reduced mitochondrial injury and mtDNA release, and consequently suppressed cGAS-STING pathway activation. Both\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      experiments showed dose-dependent decreases in pro-inflammatory factors, along with improved neurological function and attenuated brain tissue pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Nimodipine attenuates secondary neuroinflammation and neuronal apoptosis after TBI by inhibiting calcium influx, decreasing mtDNA release, and suppressing cGAS-STING signaling. These results suggest that the Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -mtDNA-cGAS-STING axis contributes to TBI pathology and that nimodipine may serve as a potential multitarget therapy.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      00, 000\u2013000.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261496716","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:03:27Z","timestamp":1792555407000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the Calcium\u2013mtDNA\u2013cGAS-STING Signaling Nexus: A Novel Redox Mechanism for Nimodipine\u2019s Neuroprotection in Traumatic Brain Injury"],"prefix":"10.1177","author":[{"given":"Xiaoming","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuning","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, Jiaxing, 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