{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:17:07Z","timestamp":1785557827426,"version":"3.56.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81660209"],"award-info":[{"award-number":["81660209"]}],"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":["82201432"],"award-info":[{"award-number":["82201432"]}],"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":["82260454"],"award-info":[{"award-number":["82260454"]}],"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":["81960221"],"award-info":[{"award-number":["81960221"]}],"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":["82071552"],"award-info":[{"award-number":["82071552"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangxi Provincial Health Commission Science and Technology Plan project","award":["202311506"],"award-info":[{"award-number":["202311506"]}]},{"name":"Jiangxi Provincial Administration of Traditional Chinese Medicine science and technology plan project","award":["2022A322"],"award-info":[{"award-number":["2022A322"]}]},{"name":"Key Projects of Jiangxi Provincial Department of Education","award":["GJJ2201902"],"award-info":[{"award-number":["GJJ2201902"]}]},{"name":"Youth Foundation of Natural Science Foundation of Jiangxi Province","award":["20224BAB216045"],"award-info":[{"award-number":["20224BAB216045"]}]},{"name":"Beijing Municipal Natural Science Foundation","award":["7212047"],"award-info":[{"award-number":["7212047"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"DOI":"10.1186\/s12916-025-04565-2","type":"journal-article","created":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T02:35:44Z","timestamp":1765074944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Normobaric hyperoxia for intracerebral hemorrhage: a randomized clinical trial"],"prefix":"10.1186","volume":"24","author":[{"given":"Zhiying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moxin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangbin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongbin","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunming","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"issue":"17","key":"4565_CR1","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMra2201449","volume":"387","author":"KN Sheth","year":"2022","unstructured":"Sheth KN. Spontaneous intracerebral hemorrhage. N Engl J Med. 2022;387(17):1589\u201396.","journal-title":"N Engl J Med"},{"issue":"6","key":"4565_CR2","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1161\/STROKEAHA.119.024965","volume":"50","author":"N Ironside","year":"2019","unstructured":"Ironside N, Chen CJ, Ding D, Mayer SA, Connolly ES Jr. Perihematomal edema after spontaneous intracerebral hemorrhage. Stroke. 2019;50(6):1626\u201333.","journal-title":"Stroke"},{"issue":"10","key":"4565_CR3","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1161\/STROKEAHA.113.001913","volume":"44","author":"M Oeinck","year":"2013","unstructured":"Oeinck M, Neunhoeffer F, Buttler KJ, Meckel S, Schmidt B, Czosnyka M, et al. Dynamic cerebral autoregulation in acute intracerebral hemorrhage. Stroke. 2013;44(10):2722\u20138.","journal-title":"Stroke"},{"issue":"6","key":"4565_CR4","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1161\/STROKEAHA.110.596718","volume":"42","author":"J Aronowski","year":"2011","unstructured":"Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011;42(6):1781\u20136.","journal-title":"Stroke"},{"issue":"1","key":"4565_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00424-7","volume":"9","author":"L Puy","year":"2023","unstructured":"Puy L, Parry-Jones AR, Sandset EC, Dowlatshahi D, Ziai W, Cordonnier C. Intracerebral haemorrhage. Nat Rev Dis Primers. 2023;9(1):14.","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"4565_CR6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00234-014-1456-6","volume":"57","author":"J Fu","year":"2015","unstructured":"Fu J, Chen WJ, Wu GY, Cheng JL, Wang MH, Zhuge Q, et al. Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage. Neuroradiology. 2015;57(2):179\u201387.","journal-title":"Neuroradiology"},{"issue":"10477","key":"4565_CR7","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/S0140-6736(24)02809-5","volume":"405","author":"W Li","year":"2025","unstructured":"Li W, Lan J, Wei M, Liu L, Hou C, Qi Z, et al. Normobaric hyperoxia combined with endovascular treatment for acute ischaemic stroke in China (OPENS-2 trial): a multicentre, randomised, single-blind, sham-controlled trial. Lancet. 2025;405(10477):486\u201397.","journal-title":"Lancet"},{"issue":"10","key":"4565_CR8","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1080\/01616412.2021.1939234","volume":"43","author":"N Li","year":"2021","unstructured":"Li N, Wu L, Zhao W, Dornbos D 3rd, Wu C, Li W, et al. Efficacy and safety of normobaric hyperoxia combined with intravenous thrombolysis on acute ischemic stroke patients. Neurol Res. 2021;43(10):809\u201314.","journal-title":"Neurol Res"},{"issue":"6","key":"4565_CR9","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/01616412.2018.1454091","volume":"40","author":"J Ding","year":"2018","unstructured":"Ding J, Zhou D, Sui M, Meng R, Chandra A, Han J, et al. The effect of normobaric oxygen in patients with acute stroke: a systematic review and meta-analysis. Neurol Res. 2018;40(6):433\u201344.","journal-title":"Neurol Res"},{"issue":"7","key":"4565_CR10","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14858","volume":"30","author":"C Li","year":"2024","unstructured":"Li C, Jiang M, Chen Z, Hu Q, Liu Z, Wang J, et al. The neuroprotective effects of normobaric oxygen therapy after stroke. CNS Neurosci Ther. 2024;30(7):e14858.","journal-title":"CNS Neurosci Ther"},{"key":"4565_CR11","doi-asserted-by":"publisher","first-page":"969","DOI":"10.2147\/CIA.S521584","volume":"20","author":"Y Duan","year":"2025","unstructured":"Duan Y, Li X, Han S, Guan J, Chen Z, Li W, et al. Normobaric hyperoxia therapy in treating stroke. Clin Interv Aging. 2025;20:969\u201381.","journal-title":"Clin Interv Aging"},{"key":"4565_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.740632","volume":"12","author":"Y Chen","year":"2021","unstructured":"Chen Y, Chen S, Chang J, Wei J, Feng M, Wang R. Perihematomal edema after intracerebral hemorrhage: an update on pathogenesis, risk factors, and therapeutic advances. Front Immunol. 2021;12:740632.","journal-title":"Front Immunol"},{"issue":"5","key":"4565_CR13","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1161\/STROKEAHA.114.008599","volume":"46","author":"J Liang","year":"2015","unstructured":"Liang J, Qi Z, Liu W, Wang P, Shi W, Dong W, et al. Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment in cerebral ischemia. Stroke. 2015;46(5):1344\u201351.","journal-title":"Stroke"},{"issue":"8","key":"4565_CR14","doi-asserted-by":"publisher","first-page":"e824","DOI":"10.1212\/WNL.0000000000200775","volume":"99","author":"W Li","year":"2022","unstructured":"Li W, Qi Z, Ma Q, Ding J, Wu C, Song H, et al. Normobaric hyperoxia combined with endovascular treatment for patients with acute ischemic stroke: a randomized controlled clinical trial. Neurology. 2022;99(8):e824\u201334.","journal-title":"Neurology"},{"issue":"7","key":"4565_CR15","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1161\/STR.0000000000000069","volume":"46","author":"JC Hemphill 3rd","year":"2015","unstructured":"Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association\/American Stroke Association. Stroke. 2015;46(7):2032\u201360.","journal-title":"Stroke"},{"issue":"7","key":"4565_CR16","doi-asserted-by":"publisher","first-page":"e282","DOI":"10.1161\/STR.0000000000000407","volume":"53","author":"SM Greenberg","year":"2022","unstructured":"Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, et al. 2022 Guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association\/American Stroke Association. Stroke. 2022;53(7):e282\u2013361.","journal-title":"Stroke"},{"issue":"7","key":"4565_CR17","volume":"2014","author":"JM Wardlaw","year":"2014","unstructured":"Wardlaw JM, Murray V, Berge E, del Zoppo GJ. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev. 2014;2014(7):CD000213.","journal-title":"Cochrane Database Syst Rev"},{"issue":"25","key":"4565_CR18","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1056\/NEJMoa1214609","volume":"368","author":"CS Anderson","year":"2013","unstructured":"Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368(25):2355\u201365.","journal-title":"N Engl J Med"},{"issue":"1","key":"4565_CR19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s12028-014-0013-9","volume":"22","author":"W Zhou","year":"2015","unstructured":"Zhou W, Marinescu M, Veltkamp R. Only very early oxygen therapy attenuates posthemorrhagic edema formation and blood-brain barrier disruption in murine intracerebral hemorrhage. Neurocrit Care. 2015;22(1):121\u201332.","journal-title":"Neurocrit Care"},{"issue":"5","key":"4565_CR20","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1161\/STROKEAHA.110.593350","volume":"42","author":"N Fujiwara","year":"2011","unstructured":"Fujiwara N, Mandeville ET, Geng X, Luo Y, Arai K, Wang X, et al. Effect of normobaric oxygen therapy in a rat model of intracerebral hemorrhage. Stroke. 2011;42(5):1469\u201372.","journal-title":"Stroke"},{"issue":"5","key":"4565_CR21","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1097\/WNR.0000000000000542","volume":"27","author":"P You","year":"2016","unstructured":"You P, Lin M, Li K, Ye X, Zheng J. Normobaric oxygen therapy inhibits HIF-1alpha and VEGF expression in perihematoma and reduces neurological function defects. NeuroReport. 2016;27(5):329\u201336.","journal-title":"NeuroReport"},{"issue":"14","key":"4565_CR22","doi-asserted-by":"publisher","first-page":"2703","DOI":"10.1089\/scd.2011.0604","volume":"21","author":"Q Zhong","year":"2012","unstructured":"Zhong Q, Zhou Y, Ye W, Cai T, Zhang X, Deng DY. Hypoxia-inducible factor 1-alpha-AA-modified bone marrow stem cells protect PC12 cells from hypoxia-induced apoptosis, partially through VEGF\/PI3K\/Akt\/FoxO1 pathway. Stem Cells Dev. 2012;21(14):2703\u201317.","journal-title":"Stem Cells Dev"},{"issue":"3","key":"4565_CR23","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14694","volume":"30","author":"M Wu","year":"2024","unstructured":"Wu M, Chen K, Zhao Y, Jiang M, Bao B, Yu W, et al. Normobaric hyperoxia alleviates complement C3-mediated synaptic pruning and brain injury after intracerebral hemorrhage. CNS Neurosci Ther. 2024;30(3):e14694.","journal-title":"CNS Neurosci Ther"},{"issue":"10","key":"4565_CR24","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1038\/sj.jcbfm.9600277","volume":"26","author":"S Liu","year":"2006","unstructured":"Liu S, Liu W, Ding W, Miyake M, Rosenberg GA, Liu KJ. Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia. J Cereb Blood Flow Metab. 2006;26(10):1274\u201384.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"4565_CR25","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1097\/01.WCB.0000110047.43905.01","volume":"24","author":"S Liu","year":"2004","unstructured":"Liu S, Shi H, Liu W, Furuichi T, Timmins GS, Liu KJ. Interstitial pO2 in ischemic penumbra and core are differentially affected following transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2004;24(3):343\u20139.","journal-title":"J Cereb Blood Flow Metab"},{"issue":"Pt 3","key":"4565_CR26","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1093\/brain\/awv391","volume":"139","author":"S Ejaz","year":"2016","unstructured":"Ejaz S, Emmrich JV, Sitnikov SL, Hong YT, Sawiak SJ, Fryer TD, et al. Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia. Brain. 2016;139(Pt 3):751\u201364.","journal-title":"Brain"},{"key":"4565_CR27","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.brainres.2010.07.010","volume":"1352","author":"Z Yuan","year":"2010","unstructured":"Yuan Z, Liu W, Liu B, Schnell A, Liu KJ. Normobaric hyperoxia delays and attenuates early nitric oxide production in focal cerebral ischemic rats. Brain Res. 2010;1352:248\u201354.","journal-title":"Brain Res"},{"issue":"5","key":"4565_CR28","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1179\/1743132812Y.0000000013","volume":"34","author":"MR Bigdeli","year":"2012","unstructured":"Bigdeli MR, Asheghabadi M, Khalili A. Time course of neuroprotection induced by normobaric hyperoxia in focal cerebral ischemia. Neurol Res. 2012;34(5):439\u201346.","journal-title":"Neurol Res"},{"issue":"1","key":"4565_CR29","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1097\/CCM.0000000000001281","volume":"44","author":"M Fallenius","year":"2016","unstructured":"Fallenius M, Raj R, Reinikainen M, Bendel S, Skrifvars MB. Association between high arterial oxygen tension and long-term survival after spontaneous intracerebral hemorrhage. Crit Care Med. 2016;44(1):180\u20137.","journal-title":"Crit Care Med"},{"issue":"1","key":"4565_CR30","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1161\/STROKEAHA.111.625756","volume":"43","author":"C Liu","year":"2012","unstructured":"Liu C, Weaver J, Liu KJ. Rapid conditioning with oxygen oscillation: neuroprotection by intermittent normobaric hyperoxia after transient focal cerebral ischemia in rats. Stroke. 2012;43(1):220\u20136.","journal-title":"Stroke"},{"issue":"2","key":"4565_CR31","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1007\/s13311-020-00979-3","volume":"18","author":"Z Cheng","year":"2021","unstructured":"Cheng Z, Geng X, Tong Y, Dornbos D 3rd, Hussain M, Rajah GB, et al. Adjuvant high-flow normobaric oxygen after mechanical thrombectomy for anterior circulation stroke: a randomized clinical trial. Neurotherapeutics. 2021;18(2):1188\u201397.","journal-title":"Neurotherapeutics"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04565-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-025-04565-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04565-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:05:23Z","timestamp":1768341923000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-025-04565-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,7]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4565"],"URL":"https:\/\/doi.org\/10.1186\/s12916-025-04565-2","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,7]]},"assertion":[{"value":"1 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of the Affiliated Hospital of Jiujiang University (Jiujiang, China, reference number 2020001). Written informed consent was obtained from all participants and\/or their legal guardians prior to their enrollment in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and agreed to the published version of the manuscript.","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":"21"}}