{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:13:12Z","timestamp":1790187192130,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ6085"],"award-info":[{"award-number":["2024JJ6085"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ40934"],"award-info":[{"award-number":["2023JJ40934"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The dorsal root ganglion (DRG) plays a critical role in mediating neuropathic pain (NP) following peripheral nerve injury (PNI), although the underlying mechanism remains unclear. This study investigated how Schwann cell (SCs)\u2010derived extracellular vesicles (SC\u2010EVs) regulate neuronal ferroptosis in NP after PNI. After validating isolated SCs (S\u2010100) and DRG neurons (NeuN), SC\u2010EVs were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting for exosomal markers (Alix\/CD9\/CD63) and the absence of Calnexin. Co\u2010localization of PKH67 with \u03b2\u2010Tubulin\u2010III confirmed SC\u2010EVs uptake by DRG neurons. Biochemical assays and flow cytometry demonstrated SC\u2010EVs suppressed ferroptosis in both LPS\u2010stimulated DRG neurons and chronic constriction injury (CCI) rat models, while simultaneously inhibiting apoptosis, inflammation, and NP progression. Mechanistically, RT\u2010qPCR and western blotting revealed aberrant expression of PPAR\u03b3, p53, SAT1, and ALOX15 in LPS\/CCI models. Co\u2010immunoprecipitation demonstrated that binding between PPAR\u03b3 and p53 inhibits SAT1\/ALOX15\u2010mediated ferroptosis in DRG neurons. Notably, SC\u2010EVs delivered MFG\u2010E8 to upregulate PPAR\u03b3 and suppress the activation of the p53\/SAT1\/ALOX15, thereby attenuating neuronal ferroptosis and ameliorating CCI\u2010induced NP. In conclusion, MFG\u2010E8 delivered via SC\u2010EVs alleviates NP after PNI by modulating the PPAR\u03b3\/p53\/SAT1\/ALOX15 signaling axis to inhibit CCI\u2010induced ferroptosis, offering novel therapeutic insights.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70288-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70288","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:51:27Z","timestamp":1762509087000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Schwann Cell\u2010Derived Extracellular Vesicles\n                    <scp>MFG<\/scp>\n                    \u2010\n                    <scp>E8<\/scp>\n                    Alleviates Neuropathic Pain After Peripheral Nerve Injury Through Inhibiting Ferroptosis in Dorsal Root Ganglion Neurons by Regulating the\n                    <scp>PPAR\u03b3<\/scp>\n                    \/p53\/\n                    <scp>SAT1<\/scp>\n                    \/\n                    <scp>ALOX15<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"169","author":[{"given":"Jiawei","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China  Changsha Hunan China"},{"name":"Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs Xuzhou Medical University  Xuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuofeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Xiangya Hospital, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6753-3103","authenticated-orcid":false,"given":"Songhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2023.04.021"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0287517"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.5812\/aapm.113020"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.119726"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.09.018"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05455-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121939"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07506-0"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1138798"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70440"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109505"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad013"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01767-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112680"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2025.105378"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107705"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00493"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114139"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14150"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1206851"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15744"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.620525"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00957-9"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201902402"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084148"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.714996"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1476718"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.4103\/0028-3886.250699"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126716"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-022-03400-0"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210920"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115680096284068240506095417"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-021-01257-9"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05528-z"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2012.03.021"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23892"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12561"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2023.101477"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-09313-w"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071740"},{"issue":"44","key":"e_1_2_12_42_1","first-page":"E6806","article-title":"Activation of SAT1 Engages Polyamine Metabolism With p53\u2010Mediated Ferroptotic Responses","volume":"113","author":"Ou Y.","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004515"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-013118-111902"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102509"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05607-4"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176820"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2021204039"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10030386"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23527"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-110920-030610"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00139-y"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03463-z"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01347-1"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04138-w"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123086"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24482"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02405-1"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05573-1"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24087"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-024-00513-1"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.12.001"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.18240"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-023-04448-3"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2053032"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109233"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-23-01539"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.827016"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001962"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.01.017"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2025.06.016"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01769-5"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c08046"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70288","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jnc.70288","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.70288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:44:10Z","timestamp":1773848650000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.70288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":72,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/jnc.70288"],"URL":"https:\/\/doi.org\/10.1111\/jnc.70288","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70288"}}