{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:17:03Z","timestamp":1788387423788,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. <jats:italic>In silico<\/jats:italic> analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, <jats:italic>histone deacetylase 1 (HDAC1)<\/jats:italic>, <jats:italic>early growth response protein 2 (EGR2)<\/jats:italic>, and <jats:italic>B cell lymphoma\/leukemia 2 (Bcl2)<\/jats:italic>. The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis <jats:italic>in vitro<\/jats:italic> as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume <jats:italic>in vivo<\/jats:italic>. hUC-MSCs-derived EVs protected against HIBD <jats:italic>in vivo<\/jats:italic> and inhibited the OGD-induced neuronal apoptosis <jats:italic>in vitro<\/jats:italic>. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted <jats:italic>HDAC1<\/jats:italic>, which inversely mediated the expression of <jats:italic>EGR2\/Bcl2<\/jats:italic>. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by <jats:italic>HDAC1<\/jats:italic> overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing <jats:italic>EGR2\/Bcl2<\/jats:italic> expression through downregulating <jats:italic>HDAC1<\/jats:italic> expression <jats:italic>in vivo<\/jats:italic>. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of <jats:italic>EGR2\/Bcl2 via HDAC1<\/jats:italic> downregulation, thereby providing a potential strategy for treating or preventing HIBD.<\/jats:p>","DOI":"10.3389\/fcell.2020.579236","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T23:22:51Z","timestamp":1610493771000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2\/Bcl2 Axis"],"prefix":"10.3389","volume":"8","author":[{"given":"Jun","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosheng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuijuan","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2016.05.018","article-title":"Cognitive deficits triggered by early life stress: the role of histone deacetylase 1.","volume":"94","author":"Adler","year":"2016","journal-title":"Neurobiol. 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