{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T22:53:36Z","timestamp":1792364016411,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuromol Med"],"DOI":"10.1007\/s12017-026-08932-x","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:16:30Z","timestamp":1779801390000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PLAUR Exacerbates Neuroinflammation in Diabetic Ischemic Stroke by Driving Neutrophil-Mediated Blood-Brain Barrier Disruption and Reprogramming Microglial Metabolism"],"prefix":"10.1007","volume":"28","author":[{"given":"Si-qi","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-ning","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-nian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-sheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-min","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"issue":"1","key":"8932_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.nbd.2009.07.030","volume":"37","author":"NJ Abbott","year":"2010","unstructured":"Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology Of Diseases, 37(1), 13\u201325. https:\/\/doi.org\/10.1016\/j.nbd.2009.07.030","journal-title":"Neurobiology Of Diseases"},{"issue":"6","key":"8932_CR2","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1046\/j.0305-1846.2000.287.x","volume":"26","author":"R Beschorner","year":"2000","unstructured":"Beschorner, R., Schluesener, H. J., Nguyen, T. D., Magdolen, V., Luther, T., Pedal, I., et al. (2000). Lesion-associated accumulation of uPAR\/CD87- expressing infiltrating granulocytes, activated microglial cells\/macrophages and upregulation by endothelial cells following TBI and FCI in humans. Neuropathology And Applied Neurobiology, 26(6), 522\u2013527. https:\/\/doi.org\/10.1046\/j.0305-1846.2000.287.x","journal-title":"Neuropathology And Applied Neurobiology"},{"key":"8932_CR3","doi-asserted-by":"publisher","unstructured":"Chaparro-Cabanillas, N., Arbaizar-Rovirosa, M., Salas-Perdomo, A., Gallizioli, M., Planas, A. M., & Justicia, C. (2023). Transient middle cerebral artery occlusion model of stroke. Journal Of Visualized Experiments : Jove, (198). https:\/\/doi.org\/10.3791\/65857","DOI":"10.3791\/65857"},{"issue":"9","key":"8932_CR4","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1016\/j.ymthe.2021.04.025","volume":"29","author":"J Chen","year":"2021","unstructured":"Chen, J., Jin, J., Zhang, X., Yu, H., Zhu, X., Yu, L., et al. (2021a). Microglial lnc-U90926 facilitates neutrophil infiltration in ischemic stroke via MDH2\/CXCL2 axis. Molecular Therapy, 29(9), 2873\u20132885. https:\/\/doi.org\/10.1016\/j.ymthe.2021.04.025","journal-title":"Molecular Therapy"},{"key":"8932_CR5","doi-asserted-by":"publisher","first-page":"784215","DOI":"10.3389\/fgene.2021.784215","volume":"12","author":"J Chen","year":"2021","unstructured":"Chen, J., Zhang, R., Xie, M., Luan, C., & Li, X. (2021b). Transcriptome sequencing identifies plaur as an important player in patients with dermatomyositis-associated interstitial lung disease. Frontiers In Genetics, 12, 784215. https:\/\/doi.org\/10.3389\/fgene.2021.784215","journal-title":"Frontiers In Genetics"},{"key":"8932_CR6","doi-asserted-by":"publisher","unstructured":"Cheng, Y. C., Sheen, J. M., Hu, W. L., & Hung, Y. C. (2017). Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke. Oxid Med Cell Longev, 2017. https:\/\/doi.org\/10.1155\/2017\/8526438","DOI":"10.1155\/2017\/8526438"},{"issue":"3","key":"8932_CR7","doi-asserted-by":"publisher","first-page":"e12982","DOI":"10.1111\/nan.12982","volume":"50","author":"SW Cheung","year":"2024","unstructured":"Cheung, S. W., Bhavnani, E., Simmons, D. G., Bellingham, M. C., & Noakes, P. G. (2024). Perineuronal nets are phagocytosed by MMP-9 expressing microglia and astrocytes in the SOD1(G93A) ALS mouse model. Neuropathology And Applied Neurobiology, 50(3), e12982. https:\/\/doi.org\/10.1111\/nan.12982","journal-title":"Neuropathology And Applied Neurobiology"},{"issue":"2","key":"8932_CR8","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.ctrv.2007.10.005","volume":"34","author":"K Dass","year":"2008","unstructured":"Dass, K., Ahmad, A., Azmi, A. S., Sarkar, S. H., & Sarkar, F. H. (2008). Evolving role of uPA\/uPAR system in human cancers. Cancer Treatment Reviews, 34(2), 122\u2013136. https:\/\/doi.org\/10.1016\/j.ctrv.2007.10.005","journal-title":"Cancer Treatment Reviews"},{"key":"8932_CR9","doi-asserted-by":"publisher","first-page":"135383","DOI":"10.1016\/j.neulet.2020.135383","volume":"738","author":"J Deng","year":"2020","unstructured":"Deng, J., Zhao, F., Zhang, Y., Zhou, Y., Xu, X., Zhang, X., et al. (2020). Neutrophil extracellular traps increased by hyperglycemia exacerbate ischemic brain damage. Neuroscience Letters, 738, 135383. https:\/\/doi.org\/10.1016\/j.neulet.2020.135383","journal-title":"Neuroscience Letters"},{"key":"8932_CR10","doi-asserted-by":"publisher","unstructured":"Denorme, F., Portier, I., Rustad, J. L., Cody, M. J., de Araujo, C. V., Hoki, C., et al. (2022). Neutrophil extracellular traps regulate ischemic stroke brain injury. J Clin Invest, 132(10). https:\/\/doi.org\/10.1172\/jci154225","DOI":"10.1172\/jci154225"},{"issue":"4","key":"8932_CR11","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s11886-019-1107-y","volume":"21","author":"D Glovaci","year":"2019","unstructured":"Glovaci, D., Fan, W., & Wong, N. D. (2019). Epidemiology of Diabetes Mellitus and Cardiovascular Disease. Current Cardiology Reports, 21(4), 21. https:\/\/doi.org\/10.1007\/s11886-019-1107-y","journal-title":"Current Cardiology Reports"},{"key":"8932_CR12","doi-asserted-by":"publisher","unstructured":"Jiang, Y., Lin, L., Liu, N., Wang, Q., Yuan, J., Li, Y., et al. (2020). FGF21 protects against aggravated blood-brain barrier disruption after ischemic focal stroke in diabetic db\/db male mice via cerebrovascular PPAR\u03b3 activation. International Journal Of Molecular Sciences, 21(3). https:\/\/doi.org\/10.3390\/ijms21030824","DOI":"10.3390\/ijms21030824"},{"key":"8932_CR13","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3389\/fphar.2012.00131","volume":"3","author":"J Kapitulnik","year":"2012","unstructured":"Kapitulnik, J., Benaim, C., & Sasson, S. (2012). Endothelial Cells Derived from the Blood-Brain Barrier and Islets of Langerhans Differ in their Response to the Effects of Bilirubin on Oxidative Stress Under Hyperglycemic Conditions. Frontiers In Pharmacology, 3, 131. https:\/\/doi.org\/10.3389\/fphar.2012.00131","journal-title":"Frontiers In Pharmacology"},{"key":"8932_CR14","doi-asserted-by":"publisher","first-page":"864858","DOI":"10.3389\/fimmu.2022.864858","volume":"13","author":"S Kim","year":"2022","unstructured":"Kim, S., Park, E. S., Chen, P. R., & Kim, E. (2022). Dysregulated hypothalamic-pituitary-adrenal axis is associated with increased inflammation and worse outcomes after ischemic stroke in diabetic mice. Frontiers In Immunology, 13, 864858. https:\/\/doi.org\/10.3389\/fimmu.2022.864858","journal-title":"Frontiers In Immunology"},{"issue":"1","key":"8932_CR15","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12951-023-01828-z","volume":"21","author":"Y Li","year":"2023","unstructured":"Li, Y., Liu, B., Zhao, T., Quan, X., Han, Y., Cheng, Y., et al. (2023). Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood-brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke. J Nanobiotechnology, 21(1), 70. https:\/\/doi.org\/10.1186\/s12951-023-01828-z","journal-title":"J Nanobiotechnology"},{"key":"8932_CR16","doi-asserted-by":"publisher","first-page":"4629","DOI":"10.2147\/jir.S326559","volume":"14","author":"M Liu","year":"2021","unstructured":"Liu, M., Chen, S., Zhang, A., Zheng, Q., & Fu, J. (2021). PLAUR as a potential biomarker associated with immune infiltration in bladder urothelial carcinoma. J Inflamm Res, 14, 4629\u20134641. https:\/\/doi.org\/10.2147\/jir.S326559","journal-title":"J Inflamm Res"},{"issue":"12","key":"8932_CR17","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.1002\/glia.70073","volume":"73","author":"Y Liu","year":"2025","unstructured":"Liu, Y., Zhang, Y., Sun, M., Dong, H., Hu, X., Shen, T., et al. (2025). Acid-Sensing PAC Channel Promotes Astrocyte Acidosis in Ischemic Stroke. Glia, 73(12), 2353\u20132368. https:\/\/doi.org\/10.1002\/glia.70073","journal-title":"Glia"},{"issue":"5","key":"8932_CR18","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1083\/jcb.200612058","volume":"177","author":"CD Madsen","year":"2007","unstructured":"Madsen, C. D., Ferraris, G. M., Andolfo, A., Cunningham, O., & Sidenius, N. (2007). uPAR-induced cell adhesion and migration: vitronectin provides the key. Journal Of Cell Biology, 177(5), 927\u2013939. https:\/\/doi.org\/10.1083\/jcb.200612058","journal-title":"Journal Of Cell Biology"},{"key":"8932_CR19","doi-asserted-by":"publisher","unstructured":"Maida, C. D., Daidone, M., Pacinella, G., Norrito, R. L., Pinto, A., & Tuttolomondo, A. (2022). Diabetes and ischemic stroke: an old and new relationship an overview of the close interaction between these diseases. International Journal Of Molecular Sciences, 23(4). https:\/\/doi.org\/10.3390\/ijms23042397","DOI":"10.3390\/ijms23042397"},{"key":"8932_CR20","doi-asserted-by":"publisher","first-page":"624387","DOI":"10.3389\/fnagi.2021.624387","volume":"13","author":"X Mi","year":"2021","unstructured":"Mi, X., Cao, Y., Li, Y., Li, Y., Hong, J., He, J., et al. (2021). The Non-peptide Angiotensin-(1\u20137) Mimic AVE 0991 Attenuates Delayed Neurocognitive Recovery After Laparotomy by Reducing Neuroinflammation and Restoring Blood-Brain Barrier Integrity in Aged Rats. Frontiers In Aging Neuroscience, 13, 624387. https:\/\/doi.org\/10.3389\/fnagi.2021.624387","journal-title":"Frontiers In Aging Neuroscience"},{"issue":"1","key":"8932_CR21","doi-asserted-by":"publisher","first-page":"26","DOI":"10.5853\/jos.2022.02306","volume":"25","author":"O Mosenzon","year":"2023","unstructured":"Mosenzon, O., Cheng, A. Y., Rabinstein, A. A., & Sacco, S. (2023). Diabetes and stroke: what are the connections? J Stroke, 25(1), 26\u201338. https:\/\/doi.org\/10.5853\/jos.2022.02306","journal-title":"J Stroke"},{"issue":"6","key":"8932_CR22","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00109-024-02441-9","volume":"102","author":"TT Oo","year":"2024","unstructured":"Oo, T. T. (2024). Ischemic stroke and diabetes: a TLR4-mediated neuroinflammatory perspective. J Mol Med (Berl), 102(6), 709\u2013717. https:\/\/doi.org\/10.1007\/s00109-024-02441-9","journal-title":"J Mol Med (Berl)"},{"key":"8932_CR23","doi-asserted-by":"publisher","first-page":"110894","DOI":"10.1016\/j.brainresbull.2024.110894","volume":"208","author":"H Qian","year":"2024","unstructured":"Qian, H., Zhang, H. N., Gao, T., Wang, X. S., Wang, X., Yu, M. Y., et al. (2024). Upregulation of TRPC1 in microglia promotes neutrophil infiltration after ischemic stroke. Brain Research Bulletin, 208, 110894. https:\/\/doi.org\/10.1016\/j.brainresbull.2024.110894","journal-title":"Brain Research Bulletin"},{"issue":"2","key":"8932_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1089\/ther.2014.0027","volume":"5","author":"M Rundgren","year":"2015","unstructured":"Rundgren, M., Lyngbaek, S., Fisker, H., & Friberg, H. (2015). The inflammatory marker suPAR after cardiac arrest. Ther Hypothermia Temp Manag, 5(2), 89\u201394. https:\/\/doi.org\/10.1089\/ther.2014.0027","journal-title":"Ther Hypothermia Temp Manag"},{"issue":"1","key":"8932_CR25","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s12974-023-02903-w","volume":"20","author":"G Shi","year":"2023","unstructured":"Shi, G., Liu, L., Cao, Y., Ma, G., Zhu, Y., Xu, J., et al. (2023). Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1\u03b1\/ASK1\/JNK signaling pathway in mice with traumatic brain injury. J Neuroinflammation, 20(1), 222. https:\/\/doi.org\/10.1186\/s12974-023-02903-w","journal-title":"J Neuroinflammation"},{"key":"8932_CR26","doi-asserted-by":"publisher","first-page":"114797","DOI":"10.1016\/j.expneurol.2024.114797","volume":"377","author":"H Wang","year":"2024","unstructured":"Wang, H., Wang, Z., Gao, Y., Wang, J., Yuan, Y., Zhang, C., et al. (2024). STZ-induced diabetes exacerbates neurons ferroptosis after ischemic stroke by upregulating LCN2 in neutrophils. Experimental Neurology, 377, 114797. https:\/\/doi.org\/10.1016\/j.expneurol.2024.114797","journal-title":"Experimental Neurology"},{"key":"8932_CR27","doi-asserted-by":"publisher","DOI":"10.1042\/cs20242943","author":"M Wei","year":"2025","unstructured":"Wei, M., Huang, Q., Yu, F., Luo, Y. F., Feng, X., Liao, D., et al. (2025). Elevated phenylacetylglutamine caused by gut dysbiosis associated with type 2 diabetes increases neutrophil extracellular traps formation and exacerbates brain infarction. Clin Sci (Lond). https:\/\/doi.org\/10.1042\/cs20242943","journal-title":"Clin Sci (Lond)"},{"issue":"2","key":"8932_CR28","doi-asserted-by":"publisher","first-page":"C135","DOI":"10.1152\/ajpcell.00136.2018","volume":"316","author":"C Yang","year":"2019","unstructured":"Yang, C., Hawkins, K. E., Dor\u00e9, S., & Candelario-Jalil, E. (2019). Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke. American Journal Of Physiology. Cell Physiology, 316(2), C135\u2013c153. https:\/\/doi.org\/10.1152\/ajpcell.00136.2018","journal-title":"American Journal Of Physiology. Cell Physiology"},{"issue":"1","key":"8932_CR29","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1186\/s12916-024-03768-3","volume":"22","author":"Z Yang","year":"2024","unstructured":"Yang, Z., Huang, C., Huang, W., Yan, C., Wen, X., Hu, D., et al. (2024). Exacerbated ischemic brain damage in type 2 diabetes via methylglyoxal-mediated miR-148a-3p decline. Bmc Medicine, 22(1), 557. https:\/\/doi.org\/10.1186\/s12916-024-03768-3","journal-title":"Bmc Medicine"},{"issue":"17","key":"8932_CR30","doi-asserted-by":"publisher","first-page":"e2305877","DOI":"10.1002\/advs.202305877","volume":"11","author":"N Yin","year":"2024","unstructured":"Yin, N., Wang, W., Pei, F., Zhao, Y., Liu, C., Guo, M., et al. (2024). A neutrophil hijacking nanoplatform reprograming NETosis for targeted microglia polarizing mediated ischemic stroke treatment. Adv Sci (Weinh), 11(17), e2305877. https:\/\/doi.org\/10.1002\/advs.202305877","journal-title":"Adv Sci (Weinh)"},{"issue":"6","key":"8932_CR32","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1159\/000519327","volume":"55","author":"L Zhang","year":"2021","unstructured":"Zhang, L., Li, X., Wolfe, C. D. A., O\u2019Connell, M. D. L., & Wang, Y. (2021). Diabetes As an Independent Risk Factor for Stroke Recurrence in Ischemic Stroke Patients: An Updated Meta-Analysis. Neuroepidemiology, 55(6), 427\u2013435. https:\/\/doi.org\/10.1159\/000519327","journal-title":"Neuroepidemiology"},{"issue":"3","key":"8932_CR33","doi-asserted-by":"publisher","first-page":"943","DOI":"10.14336\/ad.2021.1029","volume":"13","author":"Q Zhang","year":"2022","unstructured":"Zhang, Q., Liu, C., Shi, R., Zhou, S., Shan, H., Deng, L., et al. (2022). Blocking C3d(+)\/GFAP(+) A1 astrocyte conversion with semaglutide attenuates blood-brain barrier disruption in mice after ischemic stroke. Aging Dis, 13(3), 943\u2013959. https:\/\/doi.org\/10.14336\/ad.2021.1029","journal-title":"Aging Dis"},{"issue":"3","key":"8932_CR31","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s10142-023-01193-y","volume":"23","author":"C Zhang","year":"2023","unstructured":"Zhang, C., Chen, S., Wang, W., & Gao, Y. (2023). YY1 regulates the proliferation and invasion of triple-negative breast cancer via activating PLAUR. Functional And Integrative Genomics, 23(3), 269. https:\/\/doi.org\/10.1007\/s10142-023-01193-y","journal-title":"Functional And Integrative Genomics"}],"container-title":["NeuroMolecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-026-08932-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12017-026-08932-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12017-026-08932-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:16:30Z","timestamp":1779801390000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12017-026-08932-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8932"],"URL":"https:\/\/doi.org\/10.1007\/s12017-026-08932-x","relation":{},"ISSN":["1559-1174"],"issn-type":[{"value":"1559-1174","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"21 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2026","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 authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The animal procedures in this study were reviewed and approved by The PLA Rocket Force Characteristic Medical Center our Animal Ethics Committee.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}},{"value":"All authors agree that the work will be published in a journal and understand and.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}],"article-number":"28"}}