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Aims This study aimed to explore that the human neural stem cell derived extracellular vesicles (hNSC-EVs) have therapeutic effect on neuronal hypoxia-reperfusion (H/R) injured neurons in vitro by mediating the nuclear translocation of NF-E2-related factor 2 (Nrf2) to regulate the expression of downstream oxidative kinases. Main methods The neuroprotective effects of hNSC-EVs were evaluated in an in vitro neuronal H/R model. Three parameters of hNSC-EVs, structure, phenotype and particle size, were characterized. At the cellular level,