{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:47:48Z","timestamp":1791884868191,"version":"4.3.4"},"reference-count":106,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["82572467"],"award-info":[{"award-number":["82572467"]}],"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":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) and spinal cord injury (SCI) induce PANoptosis, a pro\u2010inflammatory programmed cell death modality orchestrated by the PANoptosome. This modality integrates pyroptosis, apoptosis, and necroptosis molecular machinery and contrasts with canonical single\u2010pathway cell death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review (PROSPERO CRD420261383435) followed PRISMA and searched PubMed, Web of Science, and Cochrane Library. The in\u00a0vivo studies confirming PANoptosis at the protein level were included; quality was assessed using CRIME\u2010Q, and shared genes\/protein interactions were analyzed via GeneCards, STRING, and Cytoscape.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten studies (five TBI and five SCI) were included. PANoptosis occurs in microglia and neurons, with significant crosstalk in secondary injury. Regulatory mechanisms included transcriptional regulation, inflammatory signaling, ubiquitination, energy metabolism, proteolysis, and mitophagy. Interventions comprised specific inhibitors, Chinese medicine formula granules, small molecules, siRNAs, drugs, metabolites, plasmids, and metal ions. Key sensors included ZBP1 and NLRP12, with ASC as the main adaptor; executioners included CASP1, GSDMD, CASP3\/8, RIPK1\/3, MLKL, and activated forms. Ischemia was the most significant disease\u2010gene network factor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The primary injury activates microglia and neurons, inducing PANoptosis via multiple pathways; targeting PANoptosome assembly may preserve immuno\u2010inflammatory balance and limit secondary damage. Future research should prioritize comprehensive PANoptosome detection, standardized animal models, CNS cell interactions, novel drug delivery, and ischemia\u2013reperfusion injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71208","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:15:51Z","timestamp":1791882951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PANoptosis In Microglia and Neurons Following Traumatic\n                    <scp>CNS<\/scp>\n                    Injury: A Systematic Review of Pathological Features and Therapeutic Implications"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7765-8922","authenticated-orcid":false,"given":"Zhusheng","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Emergency Xijing Hospital, The Fourth Military Medical University  Xi'an Shaanxi 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