{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:50:15Z","timestamp":1768387815376,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"DOI":"10.1186\/s12974-025-03653-7","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T10:06:42Z","timestamp":1765447602000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Remimazolam attenuates traumatic brain injury-induced acute lung injury by suppressing pulmonary epithelial pyroptosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Chang","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bailun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angran","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuelan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changping","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"3653_CR1","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1002\/msj.20100","volume":"76","author":"CR Summers","year":"2009","unstructured":"Summers CR, Ivins B, Schwab KA. Traumatic brain injury in the United States: an epidemiologic overview. Mt Sinai J Med. 2009;76:105\u201310.","journal-title":"Mt Sinai J Med"},{"key":"3653_CR2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40560-016-0138-3","volume":"4","author":"K Kinoshita","year":"2016","unstructured":"Kinoshita K. Traumatic brain injury: pathophysiology for neurocritical care. J Intensive Care. 2016;4:29.","journal-title":"J Intensive Care"},{"key":"3653_CR3","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1097\/TA.0000000000000903","volume":"80","author":"IP Aisiku","year":"2016","unstructured":"Aisiku IP, Yamal JM, Doshi P, Rubin ML, Benoit JS, Hannay J, Tilley BC, Gopinath S, Robertson CS. The incidence of ARDS and associated mortality in severe TBI using the Berlin definition. J Trauma Acute Care Surg. 2016;80:308\u201312.","journal-title":"J Trauma Acute Care Surg"},{"key":"3653_CR4","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nature15514","volume":"526","author":"J Shi","year":"2015","unstructured":"Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526:660\u20135.","journal-title":"Nature"},{"key":"3653_CR5","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41419-019-1761-4","volume":"10","author":"L Sun","year":"2019","unstructured":"Sun L, Ma W, Gao W, Xing Y, Chen L, Xia Z, Zhang Z, Dai Z. Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome. Cell Death Dis. 2019;10:542.","journal-title":"Cell Death Dis"},{"key":"3653_CR6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.59249\/XCAB1680","volume":"98","author":"Z Bagheri","year":"2025","unstructured":"Bagheri Z, Abuei H, Jaafari A, Taki S, Arsanjani AA, Farhadi A. Inhibition of p16 and NF-\u03baB oncogenic activity in human Papillomavirus-infected cervical cancer cells: a new role for activating transcription Factor-3. Yale J Biol Med. 2025;98:21\u201332.","journal-title":"Yale J Biol Med"},{"key":"3653_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0378-1119(01)00551-0","volume":"273","author":"T Hai","year":"2001","unstructured":"Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor\/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis. Gene. 2001;273:1\u201311.","journal-title":"Gene"},{"key":"3653_CR8","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1002\/jcp.25849","volume":"232","author":"L Qian","year":"2017","unstructured":"Qian L, Zhao Y, Guo L, Li S, Wu X. Activating transcription factor 3 (ATF3) protects against lipopolysaccharide-induced acute lung injury via inhibiting the expression of TL1A. J Cell Physiol. 2017;232:3727\u201334.","journal-title":"J Cell Physiol"},{"key":"3653_CR9","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/ni.2784","volume":"15","author":"D De Nardo","year":"2014","unstructured":"De Nardo D, Labzin LI, Kono H, Seki R, Schmidt SV, Beyer M, Xu D, Zimmer S, Lahrmann C, Schildberg FA, et al. High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol. 2014;15:152\u201360.","journal-title":"Nat Immunol"},{"key":"3653_CR10","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1016\/j.molimm.2006.08.006","volume":"44","author":"CH Khuu","year":"2007","unstructured":"Khuu CH, Barrozo RM, Hai T, Weinstein SL. Activating transcription factor 3 (ATF3) represses the expression of CCL4 in murine macrophages. Mol Immunol. 2007;44:1598\u2013605.","journal-title":"Mol Immunol"},{"key":"3653_CR11","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1089\/ars.2014.5987","volume":"22","author":"Y Shan","year":"2015","unstructured":"Shan Y, Akram A, Amatullah H, Zhou DY, Gali PL, Maron-Gutierrez T, Gonz\u00e1lez-L\u00f3pez A, Zhou L, Rocco PR, Hwang D, et al. ATF3 protects pulmonary resident cells from acute and ventilator-induced lung injury by preventing Nrf2 degradation. Antioxid Redox Signal. 2015;22:651\u201368.","journal-title":"Antioxid Redox Signal"},{"key":"3653_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01954","volume":"9","author":"S Lee","year":"2018","unstructured":"Lee S, Kim GL, Kim NY, Kim SJ, Ghosh P, Rhee DK. ATF3 stimulates IL-17A by regulating intracellular Ca(2+)\/ROS-dependent IL-1\u03b2 activation during Streptococcus pneumoniae infection. Front Immunol. 2018;9:1954.","journal-title":"Front Immunol"},{"key":"3653_CR13","doi-asserted-by":"publisher","first-page":"3957","DOI":"10.2147\/DDDT.S384155","volume":"16","author":"Q Hu","year":"2022","unstructured":"Hu Q, Liu X, Wen C, Li D, Lei X. Remimazolam: an updated review of a new sedative and anaesthetic. Drug Des Devel Ther. 2022;16:3957\u201374.","journal-title":"Drug Des Devel Ther"},{"key":"3653_CR14","doi-asserted-by":"publisher","first-page":"e14438","DOI":"10.1111\/cbdd.14438","volume":"103","author":"M Yang","year":"2024","unstructured":"Yang M, Li L. Remimazolam attenuates inflammation in Bronchopneumonia through the Inhibition of NLRP3 activity by PDPK1 ubiquitination. Chem Biol Drug Des. 2024;103:e14438.","journal-title":"Chem Biol Drug Des"},{"key":"3653_CR15","doi-asserted-by":"publisher","first-page":"108331","DOI":"10.1016\/j.intimp.2021.108331","volume":"101","author":"H Fang","year":"2021","unstructured":"Fang H, Zhang Y, Wang J, Li L, An S, Huang Q, Chen Z, Yang H, Wu J, Zeng Z. Remimazolam reduces sepsis-associated acute liver injury by activation of peripheral benzodiazepine receptors and p38 Inhibition of macrophages. Int Immunopharmacol. 2021;101:108331.","journal-title":"Int Immunopharmacol"},{"key":"3653_CR16","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12974-017-0819-4","volume":"14","author":"A Kumar","year":"2017","unstructured":"Kumar A, Stoica BA, Loane DJ, Yang M, Abulwerdi G, Khan N, Kumar A, Thom SR, Faden AI. Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury. J Neuroinflammation. 2017;14:47.","journal-title":"J Neuroinflammation"},{"key":"3653_CR17","doi-asserted-by":"publisher","first-page":"113949","DOI":"10.1016\/j.intimp.2024.113949","volume":"147","author":"R Li","year":"2025","unstructured":"Li R, Zhang C, Ren J, Deng G, Gao Y, Gao X, Li J, Zhang J, Xu X, Jin X, et al. Remimazolam inhibits apoptosis of endothelial and epithelial cells by activating the PI3K\/AKT pathway in acute lung injury. Int Immunopharmacol. 2025;147:113949.","journal-title":"Int Immunopharmacol"},{"key":"3653_CR18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.molimm.2023.03.013","volume":"157","author":"H Wu","year":"2023","unstructured":"Wu H, Yan X, Zhao L, Li X, Li X, Zhang Y, Gu C, Yang F, Yan J, Lou Y, et al. p120-catenin promotes innate antiviral immunity through stabilizing TBK1-IRF3 complex. Mol Immunol. 2023;157:8\u201317.","journal-title":"Mol Immunol"},{"key":"3653_CR19","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s13054-023-04488-5","volume":"27","author":"P Ding","year":"2023","unstructured":"Ding P, Yang R, Li C, Fu HL, Ren GL, Wang P, Zheng DY, Chen W, Yang LY, Mao YF, et al. Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3\/caspase-1\/GSDMD pyroptotic pathway. Crit Care. 2023;27:196.","journal-title":"Crit Care"},{"key":"3653_CR20","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s00424-016-1917-3","volume":"469","author":"OH Wittekindt","year":"2017","unstructured":"Wittekindt OH. Tight junctions in pulmonary epithelia during lung inflammation. Pflugers Arch. 2017;469:135\u201347.","journal-title":"Pflugers Arch"},{"key":"3653_CR21","first-page":"251","volume":"33","author":"A Kuehn","year":"2016","unstructured":"Kuehn A, Kletting S, de Souza Carvalho-Wodarz C, Repnik U, Griffiths G, Fischer U, Meese E, Huwer H, Wirth D, May T, et al. Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier. Altex. 2016;33:251\u201360.","journal-title":"Altex"},{"key":"3653_CR22","doi-asserted-by":"publisher","first-page":"L885","DOI":"10.1152\/ajplung.00023.2021","volume":"321","author":"CN Zhang","year":"2021","unstructured":"Zhang CN, Li FJ, Zhao ZL, Zhang JN. The role of extracellular vesicles in traumatic brain injury-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2021;321:L885\u201391.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"3653_CR23","doi-asserted-by":"crossref","unstructured":"Huertas A, Guignabert C, Barber\u00e0 JA, B\u00e4rtsch P, Bhattacharya J, Bhattacharya S, et al. Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases: highlights from basic research to therapy. Eur Respir J. 2018;51(4):1700745.","DOI":"10.1183\/13993003.00745-2017"},{"key":"3653_CR24","doi-asserted-by":"crossref","unstructured":"Nova Z, Skovierova H, Calkovska A. Alveolar-Capillary Membrane-Related pulmonary cells as a target in Endotoxin-Induced acute lung injury. Int J Mol Sci. 2019;20(4):831.","DOI":"10.3390\/ijms20040831"},{"key":"3653_CR25","doi-asserted-by":"publisher","first-page":"e70189","DOI":"10.1111\/cns.70189","volume":"30","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Sun C, Wang B, Gu A, Zhou Z, Gu C. Brain-Derived Exosomal miR-9-5p induces ferroptosis in traumatic brain injury-Induced acute lung injury by targeting Scd1. CNS Neurosci Ther. 2024;30:e70189.","journal-title":"CNS Neurosci Ther"},{"key":"3653_CR26","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/s13054-016-1470-7","volume":"20","author":"IP Aisiku","year":"2016","unstructured":"Aisiku IP, Yamal JM, Doshi P, Benoit JS, Gopinath S, Goodman JC, Robertson CS. Plasma cytokines IL-6, IL-8, and IL-10 are associated with the development of acute respiratory distress syndrome in patients with severe traumatic brain injury. Crit Care. 2016;20:288.","journal-title":"Crit Care"},{"key":"3653_CR27","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1089\/neu.2017.5430","volume":"35","author":"NA Kerr","year":"2018","unstructured":"Kerr NA, de Rivero Vaccari JP, Abbassi S, Kaur H, Zambrano R, Wu S, Dietrich WD, Keane RW. Traumatic brain Injury-Induced acute lung injury: evidence for activation and Inhibition of a Neural-Respiratory-Inflammasome axis. J Neurotrauma. 2018;35:2067\u201376.","journal-title":"J Neurotrauma"},{"key":"3653_CR28","doi-asserted-by":"publisher","first-page":"113080","DOI":"10.1016\/j.expneurol.2019.113080","volume":"323","author":"N Kerr","year":"2020","unstructured":"Kerr N, de Rivero Vaccari JP, Dietrich WD, Keane RW. Neural-respiratory inflammasome axis in traumatic brain injury. Exp Neurol. 2020;323:113080.","journal-title":"Exp Neurol"},{"key":"3653_CR29","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1097\/SHK.0000000000001618","volume":"55","author":"M Saber","year":"2021","unstructured":"Saber M, Rice AD, Christie I, Roberts RG, Knox KS, Nakaji P, Rowe RK, Wang T, Lifshitz J. Remote ischemic conditioning reduced acute lung injury after traumatic brain injury in the mouse. Shock. 2021;55:256\u201367.","journal-title":"Shock"},{"key":"3653_CR30","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1097\/00003246-199711000-00030","volume":"25","author":"KM Smith","year":"1997","unstructured":"Smith KM, Mrozek JD, Simonton SC, Bing DR, Meyers PA, Connett JE, Mammel MC. Prolonged partial liquid ventilation using conventional and high-frequency ventilatory techniques: gas exchange and lung pathology in an animal model of respiratory distress syndrome. Crit Care Med. 1997;25:1888\u201397.","journal-title":"Crit Care Med"},{"key":"3653_CR31","doi-asserted-by":"publisher","first-page":"148975","DOI":"10.1016\/j.brainres.2024.148975","volume":"1838","author":"T Wen","year":"2024","unstructured":"Wen T, Wen J, Yao C. Remimazolam inhibits postoperative cognitive impairment after cardiopulmonary bypass by alleviating neuroinflammation and promoting microglia M2 polarization. Brain Res. 2024;1838:148975.","journal-title":"Brain Res"},{"key":"3653_CR32","doi-asserted-by":"publisher","first-page":"975","DOI":"10.2147\/DDDT.S195412","volume":"13","author":"B Ye","year":"2019","unstructured":"Ye B, Chen X, Dai S, Han J, Liang X, Lin S, Cai X, Huang Z, Huang W. Emodin alleviates myocardial ischemia\/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes. Drug Des Devel Ther. 2019;13:975\u201390.","journal-title":"Drug Des Devel Ther"},{"key":"3653_CR33","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.2337\/db17-1395","volume":"67","author":"MB Allison","year":"2018","unstructured":"Allison MB, Pan W, MacKenzie A, Patterson C, Shah K, Barnes T, Cheng W, Rupp A, Olson DP, Myers MG Jr. Defining the transcriptional targets of leptin reveals a role for Atf3 in leptin action. Diabetes. 2018;67:1093\u2013104.","journal-title":"Diabetes"},{"key":"3653_CR34","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1164\/rccm.200906-0925OC","volume":"182","author":"A Akram","year":"2010","unstructured":"Akram A, Han B, Masoom H, Peng C, Lam E, Litvack ML, Bai X, Shan Y, Hai T, Batt J, et al. Activating transcription factor 3 confers protection against ventilator-induced lung injury. Am J Respir Crit Care Med. 2010;182:489\u2013500.","journal-title":"Am J Respir Crit Care Med"},{"key":"3653_CR35","doi-asserted-by":"publisher","first-page":"413","DOI":"10.2147\/JIR.S297081","volume":"14","author":"D Luo","year":"2021","unstructured":"Luo D, Liu F, Zhang J, Shao Q, Tao W, Xiao R, et al. Comprehensive analysis of LncRNA-mRNA expression profiles and the CeRNA network associated with pyroptosis in LPS-induced acute lung injury. J Inflamm Res. 2021;14:413\u201328.","journal-title":"J Inflamm Res"},{"key":"3653_CR36","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1084\/jem.20072254","volume":"205","author":"M Gilchrist","year":"2008","unstructured":"Gilchrist M, Henderson WR, Jr., Clark AE, Simmons RM, Ye X, Smith KD, Aderem A: Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammation. J Exp Med 2008, 205:2349-2357.","journal-title":"J Exp Med"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03653-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-025-03653-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-025-03653-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:12:45Z","timestamp":1768367565000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12974-025-03653-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3653"],"URL":"https:\/\/doi.org\/10.1186\/s12974-025-03653-7","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"assertion":[{"value":"12 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"<!--Emphasis Type='Bold' removed-->Contributions"}},{"value":"All animal experiments conducted in this study were approved by the Laboratory Animal Ethics Committee of Shandong First Medical University (Approval No. W202406120616).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors gave their consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16"}}