{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T23:35:22Z","timestamp":1780961722234,"version":"3.54.1"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072168"],"award-info":[{"award-number":["82072168"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211044"],"award-info":[{"award-number":["BK20211044"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) remains a major global public health challenge with high morbidity and mortality, and secondary injury characterized by neuroinflammation, brain edema, and neuronal cell death is a critical determinant of patient prognosis. Neutrophil extracellular traps (NETs) and necroptosis are involved in TBI pathology, but their crosstalk remains unclear. Here, we used NETs inhibitors (Cl\u2010amidine and DNase I) and the necroptosis inhibitor Necrostatin\u20101 (Nec\u20101) to investigate the roles of NETs and necroptosis in neuronal injury following TBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Male C57BL\/6J mice were used to establish a TBI model via controlled cortical impact (CCI). Cl\u2010amidine, DNase I, and Necrostatin\u20101 were administered to explore the mechanism by which NETs regulate necroptosis and exacerbate TBI\u2010induced secondary injury. The modified neurological severity score (mNSS) assessment, brain edema measurement, enzyme\u2010linked immunosorbent assay (ELISA), Western blotting, immunofluorescence staining, and TUNEL staining were performed in this study. Mice were sacrificed at 1, 3, 5, and 7 days post\u2010TBI, with Day 3 post\u2010TBI designated as the key time point for primary analyses due to the peak expression of NETs markers: myeloperoxidase (MPO) and peptidyl arginine deiminase 4 (PAD4).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Finding<\/jats:title>\n                    <jats:p>Our results showed that TBI induced a time\u2010dependent upregulation of MPO and PAD4 in the ipsilateral cortex. Inhibition of NETs or blockade of necroptosis significantly reduced neuronal apoptosis, alleviated brain edema, improved mNSS scores, preserved blood\u2013brain barrier integrity, and decreased levels of pro\u2010inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2). Western blot analysis revealed that TBI markedly upregulated the expression of RIP1, RIP3, MLKL, and their phosphorylated forms, while NETs inhibition downregulated these necroptosis\u2010related proteins. Notably, combined inhibition of NETs and necroptosis did not exert synergistic protective effects on TBI\u2010induced brain injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NETs exacerbate TBI\u2010induced secondary brain injury partially by activating the necroptosis pathway. Inhibition of NETs exerts neuroprotective effects. Targeting NETs may serve as a promising therapeutic strategy to improve prognosis in TBI patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71275","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:00:27Z","timestamp":1773136827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Study on the Function and Mechanism of Neutrophil Extracellular Traps in Regulating Necroptosis Following Traumatic Brain Injury"],"prefix":"10.1002","volume":"16","author":[{"given":"Ao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Wuxi Clinical College of Anhui Medical University (The 904th Hospital of PLA)\/Fifth Clinical Medical College of Anhui Medical University  Wuxi Jiangsu Province 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