{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:15:53Z","timestamp":1791573353045,"version":"4.3.4"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Joint Logistics Medical Key Specialty Program","award":["LQZD-SW"],"award-info":[{"award-number":["LQZD-SW"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-025-04572-3","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T16:22:45Z","timestamp":1759854165000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intranasal delivery of hypoxia-preconditioned extracellular vesicles derived from BMSCs alleviates neuroinflammation and brain dysfunction in TBI"],"prefix":"10.1186","volume":"16","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingshu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohuai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shousen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"1","key":"4572_CR1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/brain\/awaa321","volume":"144","author":"AAB Jamjoom","year":"2021","unstructured":"Jamjoom AAB, Rhodes J, Andrews PJD, Grant SGN. The synapse in traumatic brain injury. Brain. 2021;144(1):18\u201331.","journal-title":"Brain"},{"issue":"2","key":"4572_CR2","doi-asserted-by":"crossref","first-page":"e12704","DOI":"10.1111\/jpi.12704","volume":"70","author":"T Rui","year":"2021","unstructured":"Rui T, Wang H, Li Q, Cheng Y, Gao Y, Fang X, et al. Deletion of ferritin H in neurons counteracts the protective effect of melatonin against traumatic brain injury-induced ferroptosis. J Pineal Res. 2021;70(2):e12704.","journal-title":"J Pineal Res"},{"issue":"12","key":"4572_CR3","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/S1474-4422(17)30371-X","volume":"16","author":"AIR Maas","year":"2017","unstructured":"Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987\u20131048.","journal-title":"Lancet Neurol"},{"issue":"3","key":"4572_CR4","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/stcltm\/szad004","volume":"12","author":"C Hering","year":"2023","unstructured":"Hering C, Shetty AK. Extracellular vesicles derived from neural stem cells, astrocytes, and microglia as therapeutics for easing TBI-Induced brain dysfunction. Stem Cells Transl Med. 2023;12(3):140\u201353.","journal-title":"Stem Cells Transl Med"},{"issue":"29","key":"4572_CR5","doi-asserted-by":"crossref","first-page":"eadp5239","DOI":"10.1126\/sciadv.adp5239","volume":"10","author":"R Jiang","year":"2024","unstructured":"Jiang R, Lu Z, Wang C, Xiao J, Liu Q, Xu X, et al. Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroinflammation in aged patients with traumatic brain injury. Sci Adv. 2024;10(29):eadp5239.","journal-title":"Sci Adv"},{"issue":"9847","key":"4572_CR6","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/S0140-6736(12)60864-2","volume":"380","author":"JV Rosenfeld","year":"2012","unstructured":"Rosenfeld JV, Maas AI, Bragge P, Morganti-Kossmann MC, Manley GT, Gruen RL. Early management of severe traumatic brain injury. Lancet. 2012;380(9847):1088\u201398.","journal-title":"Lancet"},{"issue":"6","key":"4572_CR7","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.neuron.2017.07.010","volume":"95","author":"YN Jassam","year":"2017","unstructured":"Jassam YN, Izzy S, Whalen M, McGavern DB, El Khoury J. Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron. 2017;95(6):1246\u201365.","journal-title":"Neuron"},{"issue":"6301","key":"4572_CR8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1126\/science.aaf6260","volume":"353","author":"MV Russo","year":"2016","unstructured":"Russo MV, McGavern DB. Inflammatory neuroprotection following traumatic brain injury. Science. 2016;353(6301):783\u20135.","journal-title":"Science"},{"issue":"4","key":"4572_CR9","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/bph.13139","volume":"173","author":"R Orihuela","year":"2016","unstructured":"Orihuela R, McPherson CA, Harry GJ. Microglial M1\/M2 polarization and metabolic States. Br J Pharmacol. 2016;173(4):649\u201365.","journal-title":"Br J Pharmacol"},{"issue":"1","key":"4572_CR10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/1673-5374.198966","volume":"12","author":"Y Xiong","year":"2017","unstructured":"Xiong Y, Mahmood A, Chopp M. Emerging potential of exosomes for treatment of traumatic brain injury. Neural Regen Res. 2017;12(1):19\u201322.","journal-title":"Neural Regen Res"},{"issue":"6983","key":"4572_CR11","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/nature02460","volume":"428","author":"LB Balsam","year":"2004","unstructured":"Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature Haematopoietic fates in ischaemic myocardium. Nature. 2004;428(6983):668\u201373.","journal-title":"Nature"},{"issue":"11","key":"4572_CR12","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.110.239848","volume":"108","author":"JO Jeong","year":"2011","unstructured":"Jeong JO, Han JW, Kim JM, Cho HJ, Park C, Lee N, et al. Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy. Circ Res. 2011;108(11):1340\u20137.","journal-title":"Circ Res"},{"key":"4572_CR13","doi-asserted-by":"crossref","first-page":"114199","DOI":"10.1016\/j.expneurol.2022.114199","volume":"357","author":"F Pischiutta","year":"2022","unstructured":"Pischiutta F, Caruso E, Cavaleiro H, Salgado AJ, Loane DJ, Zanier ER. Mesenchymal stromal cell secretome for traumatic brain injury: focus on Immunomodulatory action. Exp Neurol. 2022;357:114199.","journal-title":"Exp Neurol"},{"issue":"6","key":"4572_CR14","doi-asserted-by":"crossref","first-page":"e346","DOI":"10.1038\/emm.2017.63","volume":"49","author":"G Lou","year":"2017","unstructured":"Lou G, Chen Z, Zheng M, Liu Y. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Exp Mol Med. 2017;49(6):e346.","journal-title":"Exp Mol Med"},{"issue":"10","key":"4572_CR15","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.4103\/1673-5374.369114","volume":"18","author":"C Liu","year":"2023","unstructured":"Liu C, Yang TH, Li HD, Li GZ, Liang J, Wang P. Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke. Neural Regen Res. 2023;18(10):2246\u201351.","journal-title":"Neural Regen Res"},{"key":"4572_CR16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fnins.2019.00014","volume":"13","author":"H Ni","year":"2019","unstructured":"Ni H, Yang S, Siaw-Debrah F, Hu J, Wu K, He Z, et al. Exosomes derived from bone mesenchymal stem cells ameliorate early inflammatory responses following traumatic brain injury. Front Neurosci. 2019;13:14.","journal-title":"Front Neurosci"},{"issue":"11","key":"4572_CR17","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.4103\/1673-5374.371376","volume":"18","author":"Z Yang","year":"2023","unstructured":"Yang Z, Liang Z, Rao J, Lin F, Lin Y, Xu X, et al. Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases: a systematic review and meta-analysis. Neural Regen Res. 2023;18(11):2406\u201312.","journal-title":"Neural Regen Res"},{"issue":"4","key":"4572_CR18","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3171\/2014.11.JNS14770","volume":"122","author":"Y Zhang","year":"2015","unstructured":"Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, et al. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg. 2015;122(4):856\u201367.","journal-title":"J Neurosurg"},{"key":"4572_CR19","doi-asserted-by":"crossref","unstructured":"Niu Q, Yang Y, Li D, Guo W, Wang C, Xu H et al. Exosomes derived from bone marrow mesenchymal stem cells alleviate ischemia-reperfusion injury and promote survival of skin flaps in rats. Life (Basel). 2022;12(10).","DOI":"10.3390\/life12101567"},{"issue":"3","key":"4572_CR20","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/stem.2298","volume":"34","author":"JD Anderson","year":"2016","unstructured":"Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear Factor-KappaB signaling. Stem Cells. 2016;34(3):601\u201313.","journal-title":"Stem Cells"},{"issue":"8","key":"4572_CR21","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1634\/stemcells.2007-1104","volume":"26","author":"I Rosova","year":"2008","unstructured":"Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 2008;26(8):2173\u201382.","journal-title":"Stem Cells"},{"issue":"6","key":"4572_CR22","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1161\/CIRCRESAHA.115.307516","volume":"118","author":"X Hu","year":"2016","unstructured":"Hu X, Xu Y, Zhong Z, Wu Y, Zhao J, Wang Y, et al. A Large-Scale investigation of Hypoxia-Preconditioned allogeneic mesenchymal stem cells for myocardial repair in nonhuman primates: paracrine activity without remuscularization. Circ Res. 2016;118(6):970\u201383.","journal-title":"Circ Res"},{"issue":"1","key":"4572_CR23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12974-020-1726-7","volume":"17","author":"W Liu","year":"2020","unstructured":"Liu W, Rong Y, Wang J, Zhou Z, Ge X, Ji C, et al. Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1\/M2 polarization. J Neuroinflammation. 2020;17(1):47.","journal-title":"J Neuroinflammation"},{"key":"4572_CR24","doi-asserted-by":"crossref","unstructured":"Boregowda SV, Booker CN, Strivelli J, Phinney DG. Mesenchymal stem\/stromal cells (MSCs) from mouse pelvic vs. Long bones exhibit disparate critical quality attributes: implications for translational studies. Cells. 2025;14(4).","DOI":"10.3390\/cells14040274"},{"issue":"1","key":"4572_CR25","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1186\/s13287-023-03552-9","volume":"14","author":"M Handke","year":"2023","unstructured":"Handke M, Rakow A, Singer D, Miebach L, Schulze F, Bekeschus S, et al. Bone marrow from periacetabular osteotomies as a novel source for human mesenchymal stromal cells. Stem Cell Res Ther. 2023;14(1):315.","journal-title":"Stem Cell Res Ther"},{"key":"4572_CR26","first-page":"326","volume":"22","author":"J Tian","year":"2023","unstructured":"Tian J, Chen W, Xiong Y, Li Q, Kong S, Li M, et al. Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis. Bioact Mater. 2023;22:326\u201342.","journal-title":"Bioact Mater"},{"issue":"3","key":"4572_CR27","first-page":"1344","volume":"15","author":"JJ Pan","year":"2024","unstructured":"Pan JJ, Qi L, Wang L, Liu C, Song Y, Mamtilahun M, et al. M2 microglial extracellular vesicles attenuated Blood-brain barrier disruption via MiR-23a-5p in cerebral ischemic mice. Aging Dis. 2024;15(3):1344\u201356.","journal-title":"Aging Dis"},{"issue":"3","key":"4572_CR28","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41418-024-01408-0","volume":"32","author":"W Weng","year":"2025","unstructured":"Weng W, He Z, Ma Z, Huang J, Han Y, Feng Q, et al. Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury. Cell Death Differ. 2025;32(3):530\u201345.","journal-title":"Cell Death Differ"},{"key":"4572_CR29","doi-asserted-by":"crossref","unstructured":"Vrooman RM, van den Berg M, Desrosiers-Gregoire G, van Engelenburg WA, Galteau ME, Lee SH et al. fMRI data acquisition and analysis for task-free, anesthetized rats. Nat Protoc. 2025.","DOI":"10.1038\/s41596-024-01110-y"},{"issue":"1","key":"4572_CR30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/jnnp-2023-331482","volume":"95","author":"T Morozumi","year":"2023","unstructured":"Morozumi T, Preziosa P, Meani A, Albergoni M, Margoni M, Pagani E, et al. Influence of cardiorespiratory fitness and MRI measures of neuroinflammation on hippocampal volume in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023;95(1):29\u201336.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"4572_CR31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s12974-023-02934-3","volume":"20","author":"JC Vincent","year":"2023","unstructured":"Vincent JC, Garnett CN, Watson JB, Higgins EK, Macheda T, Sanders L, et al. IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury. J Neuroinflammation. 2023;20(1):248.","journal-title":"J Neuroinflammation"},{"key":"4572_CR32","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.reth.2023.04.004","volume":"23","author":"R Farahzadi","year":"2023","unstructured":"Farahzadi R, Fathi E, Mesbah-Namin SA, Vietor I. Granulocyte differentiation of rat bone marrow resident C-kit(+) hematopoietic stem cells induced by mesenchymal stem cells could be considered as new option in cell-based therapy. Regen Ther. 2023;23:94\u2013101.","journal-title":"Regen Ther"},{"key":"4572_CR33","doi-asserted-by":"crossref","first-page":"101797","DOI":"10.1016\/j.trim.2023.101797","volume":"77","author":"R Farahzadi","year":"2023","unstructured":"Farahzadi R, Valipour B, Anakok OF, Fathi E, Montazersaheb S. The effects of encapsulation on NK cell differentiation potency of C-kit\u2009+\u2009hematopoietic stem cells via identifying cytokine profiles. Transpl Immunol. 2023;77:101797.","journal-title":"Transpl Immunol"},{"issue":"1","key":"4572_CR34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12951-022-01273-4","volume":"20","author":"C Liu","year":"2022","unstructured":"Liu C, Hu F, Jiao G, Guo Y, Zhou P, Zhang Y, et al. Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFkappaB P65 signaling pathway after spinal cord injury. J Nanobiotechnol. 2022;20(1):65.","journal-title":"J Nanobiotechnol"},{"issue":"7","key":"4572_CR35","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1177\/1545968320926164","volume":"34","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Zhang Y, Chopp M, Zhang ZG, Mahmood A, Xiong Y. Mesenchymal stem cell-derived exosomes improve functional recovery in rats after traumatic brain injury: a dose-response and therapeutic window study. Neurorehabil Neural Repair. 2020;34(7):616\u201326.","journal-title":"Neurorehabil Neural Repair"},{"key":"4572_CR36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fbioe.2020.00146","volume":"8","author":"A Casado-Diaz","year":"2020","unstructured":"Casado-Diaz A, Quesada-Gomez JM, Dorado G. Extracellular vesicles derived from mesenchymal stem cells (MSC) in regenerative medicine: applications in skin wound healing. Front Bioeng Biotechnol. 2020;8:146.","journal-title":"Front Bioeng Biotechnol"},{"issue":"7","key":"4572_CR37","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4252\/wjsc.v14.i7.453","volume":"14","author":"V Pulido-Escribano","year":"2022","unstructured":"Pulido-Escribano V, Torrecillas-Baena B, Camacho-Cardenosa M, Dorado G, Galvez-Moreno MA, Casado-Diaz A. Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. World J Stem Cells. 2022;14(7):453\u201372.","journal-title":"World J Stem Cells"},{"issue":"1","key":"4572_CR38","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1186\/s13287-019-1436-1","volume":"10","author":"KA Jha","year":"2019","unstructured":"Jha KA, Pentecost M, Lenin R, Gentry J, Klaic L, Del Mar N, et al. TSG-6 in conditioned media from adipose mesenchymal stem cells protects against visual deficits in mild traumatic brain injury model through neurovascular modulation. Stem Cell Res Ther. 2019;10(1):318.","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"4572_CR39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12964-022-00862-y","volume":"20","author":"L Cai","year":"2022","unstructured":"Cai L, Gong Q, Qi L, Xu T, Suo Q, Li X, et al. ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT\/NFkappaB\/NLRP3 pathway. Cell Commun Signal. 2022;20(1):56.","journal-title":"Cell Commun Signal"},{"key":"4572_CR40","doi-asserted-by":"crossref","unstructured":"Mavroudis I, Balmus IM, Ciobica A, Nicoara MN, Luca AC, Palade DO. The role of microglial exosomes and miR-124-3p in neuroinflammation and neuronal repair after traumatic brain injury. Life (Basel). 2023;13(9).","DOI":"10.3390\/life13091924"},{"issue":"18","key":"4572_CR41","doi-asserted-by":"crossref","first-page":"979","DOI":"10.21037\/atm-22-3970","volume":"10","author":"S Qian","year":"2022","unstructured":"Qian S, Qian L, Yang Y, Cui J, Zhao Y. Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon\/caspase-1\/GSDMD in microglia. Ann Transl Med. 2022;10(18):979.","journal-title":"Ann Transl Med"},{"issue":"10","key":"4572_CR42","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1080\/15384101.2021.1919825","volume":"20","author":"Z Jiang","year":"2021","unstructured":"Jiang Z, Zhang J. Mesenchymal stem cell-derived exosomes containing miR-145-5p reduce inflammation in spinal cord injury by regulating the TLR4\/NF-kappaB signaling pathway. Cell Cycle. 2021;20(10):993\u20131009.","journal-title":"Cell Cycle"},{"issue":"3","key":"4572_CR43","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1538\/expanim.20-0160","volume":"70","author":"L Tan","year":"2021","unstructured":"Tan L, Liu L, Yao J, Piao C. miR-145-5p attenuates inflammatory response and apoptosis in myocardial ischemia-reperfusion injury by inhibiting (NADPH) oxidase homolog 1. Exp Anim. 2021;70(3):311\u201321.","journal-title":"Exp Anim"},{"issue":"4","key":"4572_CR44","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1002\/jcp.26228","volume":"233","author":"J Wu","year":"2018","unstructured":"Wu J, He Y, Luo Y, Zhang L, Lin H, Liu X, et al. MiR-145-5p inhibits proliferation and inflammatory responses of RMC through regulating AKT\/GSK pathway by targeting CXCL16. J Cell Physiol. 2018;233(4):3648\u201359.","journal-title":"J Cell Physiol"},{"issue":"1","key":"4572_CR45","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1080\/21691401.2019.1626406","volume":"47","author":"S Ma","year":"2019","unstructured":"Ma S, Zhang C, Zhang Z, Dai Y, Gu R, Jiang R. Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p. Artif Cells Nanomed Biotechnol. 2019;47(1):2875\u201381.","journal-title":"Artif Cells Nanomed Biotechnol"},{"issue":"2","key":"4572_CR46","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1080\/21655979.2022.2026548","volume":"13","author":"Z Zhu","year":"2022","unstructured":"Zhu Z, Zhang G, Li D, Yin X, Wang T. Silencing of specificity protein 1 protects H9c2 cells against lipopolysaccharide-induced injury via binding to the promoter of chemokine CXC receptor 4 and suppressing NF-kappaB signaling. Bioengineered. 2022;13(2):3395\u2013409.","journal-title":"Bioengineered"},{"key":"4572_CR47","doi-asserted-by":"crossref","unstructured":"Mei LL, Wang WJ, Qiu YT, Xie XF, Bai J, Shi ZZ. miR-145-5p suppresses tumor cell migration, invasion and epithelial to mesenchymal transition by regulating the Sp1\/NF-kappaB signaling pathway in esophageal squamous cell carcinoma. Int J Mol Sci. 2017;18(9).","DOI":"10.3390\/ijms18091833"},{"issue":"2","key":"4572_CR48","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.mcna.2019.11.001","volume":"104","author":"A Capizzi","year":"2020","unstructured":"Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: an overview of epidemiology, pathophysiology, and medical management. Med Clin North Am. 2020;104(2):213\u201338.","journal-title":"Med Clin North Am"},{"issue":"10\u201311","key":"4572_CR49","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/pmic.201200373","volume":"13","author":"T Katsuda","year":"2013","unstructured":"Katsuda T, Kosaka N, Takeshita F, Ochiya T. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. Proteomics. 2013;13(10\u201311):1637\u201353.","journal-title":"Proteomics"},{"issue":"2","key":"4572_CR50","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00018-017-2595-9","volume":"75","author":"NP Hessvik","year":"2018","unstructured":"Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018;75(2):193\u2013208.","journal-title":"Cell Mol Life Sci"},{"issue":"9","key":"4572_CR51","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1161\/CIRCRESAHA.110.226456","volume":"107","author":"SF Mause","year":"2010","unstructured":"Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res. 2010;107(9):1047\u201357.","journal-title":"Circ Res"},{"issue":"6","key":"4572_CR52","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/j.ymthe.2021.04.020","volume":"29","author":"J Ruan","year":"2021","unstructured":"Ruan J, Miao X, Schluter D, Lin L, Wang X. Extracellular vesicles in neuroinflammation: pathogenesis, diagnosis, and therapy. Mol Ther. 2021;29(6):1946\u201357.","journal-title":"Mol Ther"},{"issue":"1","key":"4572_CR53","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13287-017-0648-5","volume":"8","author":"Y Li","year":"2017","unstructured":"Li Y, Yang YY, Ren JL, Xu F, Chen FM, Li A. Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1\/M2 polarization in rats. Stem Cell Res Ther. 2017;8(1):198.","journal-title":"Stem Cell Res Ther"},{"issue":"2","key":"4572_CR54","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/SHK.0000000000001889","volume":"57","author":"T Bambakidis","year":"2022","unstructured":"Bambakidis T, Dekker SE, Williams AM, Biesterveld BE, Bhatti UF, Liu B, et al. Early treatment with a single dose of mesenchymal stem cell derived extracellular vesicles modulates the brain transcriptome to create neuroprotective changes in a porcine model of traumatic brain injury and hemorrhagic shock. Shock. 2022;57(2):281\u201390.","journal-title":"Shock"},{"issue":"1","key":"4572_CR55","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s13287-022-03083-9","volume":"13","author":"YC Ye","year":"2022","unstructured":"Ye YC, Chang ZH, Wang P, Wang YW, Liang J, Chen C, et al. Infarct-preconditioning exosomes of umbilical cord mesenchymal stem cells promoted vascular remodeling and neurological recovery after stroke in rats. Stem Cell Res Ther. 2022;13(1):378.","journal-title":"Stem Cell Res Ther"},{"key":"4572_CR56","first-page":"375","volume":"39","author":"C Chen","year":"2024","unstructured":"Chen C, Chang ZH, Yao B, Liu XY, Zhang XW, Liang J, et al. 3D printing of interferon gamma-preconditioned NSC-derived exosomes\/collagen\/chitosan biological scaffolds for neurological recovery after TBI. Bioact Mater. 2024;39:375\u201391.","journal-title":"Bioact Mater"},{"issue":"2","key":"4572_CR57","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4252\/wjsc.v16.i2.58","volume":"16","author":"XX Wan","year":"2024","unstructured":"Wan XX, Hu XM, Xiong K. Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells. World J Stem Cells. 2024;16(2):58\u201363.","journal-title":"World J Stem Cells"},{"issue":"22","key":"4572_CR58","doi-asserted-by":"crossref","first-page":"6163","DOI":"10.7150\/thno.28021","volume":"8","author":"LP Zhu","year":"2018","unstructured":"Zhu LP, Tian T, Wang JY, He JN, Chen T, Pan M, et al. Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction. Theranostics. 2018;8(22):6163\u201377.","journal-title":"Theranostics"},{"key":"4572_CR59","first-page":"584","volume":"13","author":"Q Li","year":"2021","unstructured":"Li Q, Xu Y, Lv K, Wang Y, Zhong Z, Xiao C, et al. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates. Sci Transl Med. 2021;13:584.","journal-title":"Sci Transl Med"},{"key":"4572_CR60","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.actbio.2019.12.020","volume":"103","author":"W Liu","year":"2020","unstructured":"Liu W, Li L, Rong Y, Qian D, Chen J, Zhou Z, et al. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater. 2020;103:196\u2013212.","journal-title":"Acta Biomater"},{"issue":"11","key":"4572_CR61","doi-asserted-by":"crossref","first-page":"4278","DOI":"10.7150\/thno.96038","volume":"14","author":"N Li","year":"2024","unstructured":"Li N, Zhao L, Geng X, Liu J, Zhang X, Hu Y, et al. Stimulation by exosomes from hypoxia-preconditioned hair follicle mesenchymal stem cells facilitates mitophagy by inhibiting the PI3K\/AKT\/mTOR signaling pathway to alleviate ulcerative colitis. Theranostics. 2024;14(11):4278\u201396.","journal-title":"Theranostics"},{"issue":"7","key":"4572_CR62","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/stem.2618","volume":"35","author":"H Gonzalez-King","year":"2017","unstructured":"Gonzalez-King H, Garcia NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepulveda P. Hypoxia inducible factor-1alpha potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells. 2017;35(7):1747\u201359.","journal-title":"Stem Cells"},{"issue":"1","key":"4572_CR63","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00395-021-00881-9","volume":"116","author":"J Gregorius","year":"2021","unstructured":"Gregorius J, Wang C, Stambouli O, Hussner T, Qi Y, Tertel T, et al. Small extracellular vesicles obtained from hypoxic mesenchymal stromal cells have unique characteristics that promote cerebral angiogenesis, brain remodeling and neurological recovery after focal cerebral ischemia in mice. Basic Res Cardiol. 2021;116(1):40.","journal-title":"Basic Res Cardiol"},{"key":"4572_CR64","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jconrel.2024.03.037","volume":"369","author":"Y Sun","year":"2024","unstructured":"Sun Y, Zhao J, Liu Q, Xu Y, Qin Y, He R, et al. Intranasal delivery of small extracellular vesicles from specific subpopulation of mesenchymal stem cells mitigates traumatic spinal cord injury. J Control Release. 2024;369:335\u201350.","journal-title":"J Control Release"},{"issue":"4","key":"4572_CR65","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1172\/JCI77716","volume":"125","author":"CJ Li","year":"2015","unstructured":"Li CJ, Cheng P, Liang MK, Chen YS, Lu Q, Wang JY, et al. MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest. 2015;125(4):1509\u201322.","journal-title":"J Clin Invest"},{"issue":"1","key":"4572_CR66","doi-asserted-by":"crossref","first-page":"1609206","DOI":"10.1080\/20013078.2019.1609206","volume":"8","author":"KW Witwer","year":"2019","unstructured":"Witwer KW, Van Balkom BWM, Bruno S, Choo A, Dominici M, Gimona M, et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles. 2019;8(1):1609206.","journal-title":"J Extracell Vesicles"},{"issue":"1","key":"4572_CR67","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s13287-020-01737-0","volume":"11","author":"H Cheng","year":"2020","unstructured":"Cheng H, Chang S, Xu R, Chen L, Song X, Wu J, et al. Hypoxia-challenged MSC-derived exosomes deliver miR-210 to attenuate post-infarction cardiac apoptosis. Stem Cell Res Ther. 2020;11(1):224.","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"4572_CR68","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1096\/fj.201801821R","volume":"33","author":"C Wang","year":"2019","unstructured":"Wang C, Zhu G, He W, Yin H, Lin F, Gou X, et al. BMSCs protect against renal ischemia-reperfusion injury by secreting exosomes loaded with miR-199a-5p that target BIP to inhibit Endoplasmic reticulum stress at the very early reperfusion stages. FASEB J. 2019;33(4):5440\u201356.","journal-title":"FASEB J"},{"issue":"6","key":"4572_CR69","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.bj.2021.11.012","volume":"45","author":"W Zhou","year":"2022","unstructured":"Zhou W, Ji L, Liu X, Tu D, Shi N, Yangqu W, et al. AIFM1, negatively regulated by miR-145-5p, aggravates hypoxia-induced cardiomyocyte injury. Biomed J. 2022;45(6):870\u201382.","journal-title":"Biomed J"},{"key":"4572_CR70","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.12659\/MSM.910986","volume":"24","author":"L Li","year":"2018","unstructured":"Li L, Mao D, Li C, Li M. miR-145-5p inhibits vascular smooth muscle cells (VSMCs) proliferation and migration by dysregulating the transforming growth Factor-b signaling cascade. Med Sci Monit. 2018;24:4894\u2013904.","journal-title":"Med Sci Monit"},{"issue":"1","key":"4572_CR71","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1038\/s41467-018-06222-0","volume":"9","author":"D Arneson","year":"2018","unstructured":"Arneson D, Zhang G, Ying Z, Zhuang Y, Byun HR, Ahn IS, et al. Single cell molecular alterations reveal target cells and pathways of concussive brain injury. Nat Commun. 2018;9(1):3894.","journal-title":"Nat Commun"},{"issue":"2","key":"4572_CR72","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3934\/mbe.2021065","volume":"18","author":"RZ Zheng","year":"2021","unstructured":"Zheng RZ, Xing J, Huang Q, Yang XT, Zhao CY, Li XY. Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury. Math Biosci Eng. 2021;18(2):1201\u201314.","journal-title":"Math Biosci Eng"},{"issue":"7","key":"4572_CR73","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1523\/JNEUROSCI.2469-20.2020","volume":"41","author":"KG Witcher","year":"2021","unstructured":"Witcher KG, Bray CE, Chunchai T, Zhao F, O\u2019Neil SM, Gordillo AJ, et al. Traumatic brain injury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia. J Neurosci. 2021;41(7):1597\u2013616.","journal-title":"J Neurosci"},{"issue":"2","key":"4572_CR74","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00018-021-04092-2","volume":"79","author":"X Wu","year":"2022","unstructured":"Wu X, Wei H, Wu JQ. Coding and long non-coding gene expression changes in the CNS traumatic injuries. Cell Mol Life Sci. 2022;79(2):123.","journal-title":"Cell Mol Life Sci"},{"issue":"7835","key":"4572_CR75","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41586-020-2795-6","volume":"587","author":"Y Li","year":"2020","unstructured":"Li Y, He X, Kawaguchi R, Zhang Y, Wang Q, Monavarfeshani A, et al. Microglia-organized scar-free spinal cord repair in neonatal mice. Nature. 2020;587(7835):613\u20138.","journal-title":"Nature"},{"key":"4572_CR76","doi-asserted-by":"crossref","first-page":"861428","DOI":"10.3389\/fgene.2022.861428","volume":"13","author":"J Xing","year":"2022","unstructured":"Xing J, Ren L, Xu H, Zhao L, Wang ZH, Hu GD, et al. Single-Cell RNA sequencing reveals cellular and transcriptional changes associated with traumatic brain injury. Front Genet. 2022;13:861428.","journal-title":"Front Genet"},{"issue":"8","key":"4572_CR77","doi-asserted-by":"crossref","first-page":"167344","DOI":"10.1016\/j.bbadis.2024.167344","volume":"1870","author":"G Zhang","year":"2024","unstructured":"Zhang G, Diamante G, Ahn IS, Palafox-Sanchez V, Cheng J, Cheng M, et al. Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex. Biochim Biophys Acta Mol Basis Dis. 2024;1870(8):167344.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"issue":"17","key":"4572_CR78","doi-asserted-by":"crossref","first-page":"e70016","DOI":"10.1096\/fj.202401117R","volume":"38","author":"C Lin","year":"2024","unstructured":"Lin C, Zhao P, Sun G, Liu N, Ji J. SCG2 mediates blood-brain barrier dysfunction and schizophrenia-like behaviors after traumatic brain injury. FASEB J. 2024;38(17):e70016.","journal-title":"FASEB J"},{"key":"4572_CR79","doi-asserted-by":"crossref","unstructured":"Li M, Hu W, Wang R, Li Z, Yu Y, Zhuo Y et al. Sp1 S-Sulfhydration induced by hydrogen sulfide inhibits inflammation via HDAC6\/MyD88\/NF-kappaB signaling pathway in Adjuvant-Induced arthritis. Antioxid (Basel). 2022;11(4).","DOI":"10.3390\/antiox11040732"},{"issue":"5","key":"4572_CR80","doi-asserted-by":"crossref","first-page":"166691","DOI":"10.1016\/j.bbadis.2023.166691","volume":"1869","author":"S Arkat","year":"2023","unstructured":"Arkat S, Poovitha S, Vijayakumar A, Dhat R, Sitasawad SL, Mahapatra NR. Regulation of peroxiredoxin-3 gene expression under basal and hyperglycemic conditions: key roles for transcription factors Sp1, CREB and NF-kappaB. Biochim Biophys Acta Mol Basis Dis. 2023;1869(5):166691.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"4572_CR81","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bbi.2015.04.008","volume":"48","author":"Y Yuan","year":"2015","unstructured":"Yuan Y, Zhu F, Pu Y, Wang D, Huang A, Hu X, et al. Neuroprotective effects of nitidine against traumatic CNS injury via inhibiting microglia activation. Brain Behav Immun. 2015;48:287\u2013300.","journal-title":"Brain Behav Immun"},{"key":"4572_CR82","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bbi.2016.12.005","volume":"61","author":"M Lagraoui","year":"2017","unstructured":"Lagraoui M, Sukumar G, Latoche JR, Maynard SK, Dalgard CL, Schaefer BC. Salsalate treatment following traumatic brain injury reduces inflammation and promotes a neuroprotective and neurogenic transcriptional response with concomitant functional recovery. Brain Behav Immun. 2017;61:96\u2013109.","journal-title":"Brain Behav Immun"}],"container-title":["Stem Cell Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04572-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04572-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04572-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T16:22:55Z","timestamp":1759854175000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04572-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4572"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04572-3","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"4 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 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":"This study: Intranasal delivery of hypoxia-preconditioned extracellular vesicles derived from BMSCs requires alleviates neuroinflammation and brain dysfunction in TBI, \u201chas been approved by the Animal Ethics Committee of Fuzong Clinical Medical College of Fujian Medical University. (Approval No. 2024-05, approved on May 22, 2024).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"544"}}