English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.  In silico  analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410,  histone deacetylase 1 (HDAC1) ,  early growth response protein 2 (EGR2) , and  B cell lymphoma/leukemia 2 (Bcl2) . 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  in vitro  as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume  in vivo . hUC-MSCs-derived EVs protected against HIBD  in vivo  and inhibited the OGD-induced neuronal apoptosis  in vitro . miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted  HDAC1 , which inversely mediated the expression of  EGR2/Bcl2 . Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by  HDAC1  overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing  EGR2/Bcl2  expression through downregulating  HDAC1  expression  in vivo . In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of  EGR2/Bcl2 via HDAC1  downregulation, thereby providing a potential strategy for treating or preventing HIBD.

frontiers in cell and developmental biology

Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis