{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:25:25Z","timestamp":1787124325387,"version":"build-2736575974"},"reference-count":95,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["82570102"],"award-info":[{"award-number":["82570102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004179","name":"Ningxia Medical University","doi-asserted-by":"publisher","award":["XJKF240310"],"award-info":[{"award-number":["XJKF240310"]}],"id":[{"id":"10.13039\/501100004179","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC1546"],"award-info":[{"award-number":["2025ZNSFSC1546"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Approximately 10%\u201330% of elderly patients experience cognitive decline after general anesthesia and surgery. However, how specific brain regions coordinate cellular and molecular networks to mediate cognitive decline remains unknown. Here, we revealed that the hippocampus, but not other cognitive\u2010related brain regions, exhibits increased blood\u2013brain barrier (BBB) permeability, leading to neuroinflammation activation and cognitive decline after general anesthesia and surgery in aged mice. Mechanistically, anesthesia and surgery induce expression of the mechanosensitive channel Piezo1 in hippocampal endothelial cells (ECs) of aged mice. Inducible EC\u2010specific deletion of Piezo1 restores hippocampal BBB integrity, inhibits neuroinflammation activation, and improves cognitive decline in aged mice following anesthesia and surgery. Conversely, injection of the Piezo1 agonist Yoda1 promotes hippocampal BBB breakdown. Moreover, activation of Piezo1 induces Nox4, which mediates hippocampal BBB breakdown and neuroinflammation activation after anesthesia and surgery in aged mice. Therapeutically, AAV\u2010BR1 transduction to brain microvascular ECs for the knockdown of endothelial Nox4 blocks Piezo1\u2010mediated hippocampal BBB breakdown and neuroinflammation activation. Overall, inhibiting the endothelial Piezo1\u2010Nox4 axis restores hippocampal BBB integrity to improve anesthesia\u2010 and surgery\u2010induced cognitive decline in aged mice, highlighting potential therapeutic strategies.<\/jats:p>","DOI":"10.1002\/mco2.70918","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:40:35Z","timestamp":1786520435000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibiting the Endothelial Mechanosensitive Channel Piezo1 Restores Hippocampal Blood\u2013Brain Barrier Integrity to Improve Anesthesia\u2010 and Surgery\u2010Induced Cognitive Decline"],"prefix":"10.1002","volume":"7","author":[{"given":"Yong","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"},{"name":"Department of Anesthesiology Zigong First People's Hospital, Zigong Academy of Medical Sciences  Zigong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-2132","authenticated-orcid":false,"given":"Chunheng","family":"Mo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingming","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi\u2010Sen","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology National Clinical Research Center for Geriatrics and The Research Units of West China (2018RU012), West China Hospital, Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine, National\u2010Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60160-X"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)33139-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2026.0656"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/anae.16545"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/JMDH.S431168"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2020.06.063"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.36985"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/anae.16365"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2022.11.014"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.34133\/2020\/4724505"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1174043"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.513"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202502034"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinane.2023.111059"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005991"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26771"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.067"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.10.003"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17040"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07314-2"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.10.010"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad126"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.12.018"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00902"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2020.08.017"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-70193-w"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.02.006"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000003368"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12877-023-04425-9"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00812-1"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014614"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000000257"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2023.110799"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-016-0249-0"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.578060"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-026-04271-y"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1289894"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0440-4"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010835"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01743-y"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.012"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14270"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25041991"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0348"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2024.105441"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-03939-6"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114782"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03261-x"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44254-025-00159-6"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A3251"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2022.01.005"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1374-3"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112290"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2022.05.025"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13901"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150492"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2025.152857"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25743"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04574-8"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01501-9"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1902165116"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102026"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23709"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.07.010"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.021"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24311"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52969-0"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2024.105702"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0150887"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2019.103930"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinane.2023.111125"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2018.11.008"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2019.1163"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1250123"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02910-x"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-042022-030946"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101638"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11101966"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16537"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124283"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101815"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705034114"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101512"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.1021129"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102309"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.007"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02849-z"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00046-4"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.07.008"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411313"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.964477"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70918","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mco2.70918","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:50:50Z","timestamp":1787122250000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":95,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/mco2.70918"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70918","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"article-number":"e70918"}}