{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:56Z","timestamp":1793413736982,"version":"4.5.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202606000-00078\/figure1\/v\/2026-04-16T195327Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Ischemic stroke remains a leading cause of disability and death, with mesenchymal stem cell\u2013derived exosomes emerging as a promising therapeutic avenue. However, the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation. In this study, we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell\u2013derived exosomes administered intravenously at an early (6 hours) or delayed (3 days) time point post-ischemia. Compared with delayed treatment, early administration of exosomes resulted in significantly superior efficacy, as evidenced by improved neurological function scores and reduced infarct volumes. Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes, including\n                    <jats:italic toggle=\"yes\">Ccl2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Ccl5<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Cxcl10<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Il-1<\/jats:italic>\n                    \u03b2,\n                    <jats:italic toggle=\"yes\">Il-6<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Itgam<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Itgax<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Tnf-\u03b1<\/jats:italic>\n                    . Metabolomic profiling of these brain tissues further identified modulation of key metabolites, including trimethylamine N-oxide, glutathione, 1-stearoyl-rac-glycerol, and phosphatidylcholine, suggesting that alteration of metabolic pathways contributes to the therapeutic effect. Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid, lysine, propanoate, and tyrosine. These findings suggest that umbilical cord mesenchymal stem cell\u2013derived exosomes, particularly when administered early post-ischemia, exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain, highlighting their potential as a therapeutic intervention for ischemic stroke.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-01219","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T08:00:10Z","timestamp":1755158410000},"page":"2632-2642","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic mechanisms of umbilical cord mesenchymal stem cell\u2013derived exosomes in ischemic stroke: A transcriptomic and metabolomic study"],"prefix":"10.4103","volume":"21","author":[{"given":"Baoxi","family":"Shen","sequence":"first","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, China"},{"name":"Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Physical Examination Center, The People\u2019s Hospital of Pizhou, Xuzhou, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the Seventh Medical Center, Chinese PLA General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Hou","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3635-604X","authenticated-orcid":false,"given":"Yiwu","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"R1-20260416","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.3390\/ijms22095010","article-title":"Glutathione in the brain","volume":"22","author":"Aoyama","year":"2021","journal-title":"Int J Mol Sci"},{"key":"R2-20260416","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.tcb.2023.06.006","article-title":"The ins-and-outs of exosome biogenesis, secretion, and internalization","volume":"34","author":"Arya","year":"2024","journal-title":"Trends Cell 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