{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:15:05Z","timestamp":1792167305416,"version":"4.4.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271298"],"award-info":[{"award-number":["82271298"]}],"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":["82271297"],"award-info":[{"award-number":["82271297"]}],"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":["82160243"],"award-info":[{"award-number":["82160243"]}],"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":["82001300"],"award-info":[{"award-number":["82001300"]}],"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":["82571671"],"award-info":[{"award-number":["82571671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014945","name":"Guangzhou Science and Technology Innovation Center","doi-asserted-by":"publisher","award":["SL2022A04J00214"],"award-info":[{"award-number":["SL2022A04J00214"]}],"id":[{"id":"10.13039\/501100014945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018684","name":"National Health Commission of the People's Republic of China","doi-asserted-by":"publisher","award":["GWJJQ2022100104"],"award-info":[{"award-number":["GWJJQ2022100104"]}],"id":[{"id":"10.13039\/501100018684","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cerebral edema and hypoperfusion, hallmark pathologies of both hemorrhagic and ischemic stroke, critically compromise clinical outcomes. Astrocytic aquaporin\u20104 (AQP4) not only drives post\u2010stroke brain edema progression but also maintains the protective clearance function of the glymphatic system. Herein, systemic AQP4 inhibition using TGN\u2010020 (TGN) paradoxically exacerbates global glymphatic dysfunction despite alleviating cerebral edema and microcirculatory dysfunction following subarachnoid hemorrhage (SAH). To overcome this therapeutic dilemma, an angiopep\u20102\u2010functionalized lipid nanoparticle (A\u2010LNP) platform enabling lesion\u2010targeted TGN delivery is engineered. This system reverses the detrimental effects of TGN on the post\u2010SAH glymphatic system while enhancing the therapeutic benefits of TGN in mitigating cerebral edema and microcirculatory dysfunction. Remarkably, TGN demonstrates multimodal efficacy in ischemic stroke by mitigating the no\u2010reflow phenomenon, alleviating blood\u2010brain barrier disruption, and suppressing neuroinflammation. The A\u2010LNP system retains the protective effects of TGN without compromising global glymphatic function, leading to enhanced therapeutic efficacy. These findings confirm the feasibility of using functional nanoparticles to enhance the protective effects of AQP4 inhibition while minimizing adverse effects on the glymphatic system, offering a promising therapeutic strategy for both stroke subtypes.<\/jats:p>","DOI":"10.1002\/advs.202520118","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:39:12Z","timestamp":1765600752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Amelioration of Post\u2010Stroke Edema and Microcirculatory Dysfunction via Targeted AQP4 Inhibition While Preserving the Glymphatic System"],"prefix":"10.1002","volume":"13","author":[{"given":"Lei","family":"Jin","sequence":"first","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Wei","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wu","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa","family":"Jin","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixing","family":"Su","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchao","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenquan","family":"Guo","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwu","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cai","sequence":"additional","affiliation":[{"name":"Nanomedicine Innovation Center Erasmus (NICE) Erasmus MC 3015 GD Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs Henan University  Zhengzhou 450046 China"},{"name":"Translational Medical Center of Huaihe Hospital Henan University  Kaifeng 475004 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital Jiangxi Medical College Nanchang University Nanchang 330006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanzhi","family":"Duan","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-1916","authenticated-orcid":false,"given":"Xifeng","family":"Li","sequence":"additional","affiliation":[{"name":"Neurosurgery Center Department of Cerebrovascular Surgery The National Key Clinical Specialty Engineering Research Center of Diagnostic and Therapeutic Technology and Devices for Cerebrovascular Diseases in Ministry of Education Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Zhujiang Hospital Institute for Brain Science and Intelligence Zhujiang Hospital, Southern Medical University Guangzhou 510282 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00921-z"},{"key":"e_1_2_9_2_1","first-page":"528","volume":"91","author":"Yew K. S.","year":"2015","journal-title":"Am. Fam. Physician"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2016.01515"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.063366"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.4346"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.024283"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.675975"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx364"},{"key":"e_1_2_9_9_1","first-page":"97","author":"Krishnan R.","year":"2021","journal-title":"Neurology"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3468"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.03.037"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad070"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/72256"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-020-00925-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24439"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.97"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.173"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.036104"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.82232"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa179"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01439-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417449"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03478-9"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0431-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.870029"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14308"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24639"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01797-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2015-0069"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.01.031"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.03.004"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03636-w"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24224"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2021.2010045"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-024-01238-9"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013210"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X241237159"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.01.017"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-024-00527-7"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.01.011"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108260"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06909-x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.796616"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2007.08.004"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202410889"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.045941"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj4260"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520118","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202520118","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202520118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:39:21Z","timestamp":1783013961000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202520118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":48,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/advs.202520118"],"URL":"https:\/\/doi.org\/10.1002\/advs.202520118","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"2025-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e20118"}}