{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:42:12Z","timestamp":1792845732396,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":305,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SAHNMU","award":["789ZYRC202080235"],"award-info":[{"award-number":["789ZYRC202080235"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Mesenchymal stem cell\u2010derived exosomes (MSC\u2010exos) have been recognized as a promising therapeutic strategy for neonatal hypoxic\u2010ischemic brain damage (HIBD). Recently, microglial pyroptosis was shown to play a vital role in the progression of neonatal HIBD. However, whether MSC\u2010exos improve HIBD by regulating microglial pyroptosis remains unknown. <jats:italic>Methods.<\/jats:italic> Exosomes were isolated from human umbilical cord mesenchymal stem cells (huMSCs) and identified by transmission electron microscopy (TEM), western blot, and nanoparticle tracking analysis (NTA). BV\u20102 cells were subjected to oxygen\u2010glucose deprivation\/reoxygenation (OGD\/R) to induce microglial ischemia\/reperfusion (I\/R) <jats:italic>in vitro<\/jats:italic>. CCK\u20108, ELISA, western blot, and Hoechst 33342\/PI double staining were performed to detect the pyroptosis of BV\u20102 cells. Conditioned medium (CM) from BV\u20102 cells exposed to different treatments was used to investigate its effect on neuronal injury. Moreover, 3\u2010methyladenine (3\u2010MA) and mitochondrial division inhibitor\u20101 (mdi\u20101) were used to verify the involvement of mitophagy in the protection of MSC\u2010exos against OGD\/R\u2010induced pyroptosis in BV\u20102 cells. Finally, FOXO3a siRNA was used to investigate the involvement of FOXO3a in MSC\u2010exo\u2010induced mitophagy and pyroptosis inhibition. <jats:italic>Results<\/jats:italic>. Exosomes from huMSCs were successfully extracted. In OGD\/R\u2010exposed BV\u20102 cells, MSC\u2010exos increased cell viability and decreased the expression of NLRP3, cleaved caspase\u20101, and GSDMD\u2010N as well as the release of IL\u20101<jats:italic>\u03b2<\/jats:italic> and IL\u201018. Compared with CM from OGD\/R\u2010exposed BV\u20102 cells treated with PBS, CM from OGD\/R\u2010exposed BV\u20102 cells treated with MSC\u2010exos significantly increased the viability of SH\u2010SY5Y cells and decreased LDH release. MSC\u2010exos also increased the expression of TOM20 and COX IV in OGD\/R\u2010exposed BV\u20102 cells. Additionally, 3\u2010MA and mdi\u20101 attenuated the inhibition of pyroptosis with MSC\u2010exo treatment. Furthermore, FOXO3a siRNA partially abolished the neuroprotective effect of MSC\u2010exos and attenuated mitophagy and pyroptosis inhibition induced by MSC\u2010exo treatment. <jats:italic>Conclusions<\/jats:italic>. Our findings demonstrated that MSC\u2010exos increased FOXO3a expression to enhance mitophagy, therefore protecting microglia from I\/R\u2010induced pyroptosis and alleviating subsequent neuronal injury.<\/jats:p>","DOI":"10.1155\/2021\/6219715","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T23:20:07Z","timestamp":1635895207000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Human Umbilical Cord Mesenchymal Stem Cell\u2010Derived Exosomes Attenuate Oxygen\u2010Glucose Deprivation\/Reperfusion\u2010Induced Microglial Pyroptosis by Promoting FOXO3a\u2010Dependent 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