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Background Neonatal hypoxia ischemia causes severe brain damage.Stem cell therapy is a promising method for treating neuronal diseases.Clinical translation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the recovery of neurons after hypoxic ischemic encephalopathy (HIE) may represent an effective therapy.Methods Primary neurons were exposed to oxygen-glucose deprivation (OGD) and subsequently cocultured with UC-MSCs.Apoptosis was examined by Annexin V-FITC-PI.Genes related to apoptosis were detected using RT-PCR and westblot analyses.Using an in vivo model,HIE was induced in postnatal day 7 mice,and UC-MSCs were transplanted via the intraventricular route.UC-MSC migration was investigated by immunofluorescence,and lesion volumes were measured by TTC staining.Apoptosis in injured brain cells was detected by the TUNEL assay.RT-PCR and ELISA were used to detect the expression of inflammatory factors in cells and animal tissues.Results Flow cytometry analysis revealed that apoptosis in injured neurons was inhibited by UC-MSCs.The RT-PCR and west blot results indicated that coculture inhibited the expression of proapoptotic genes and upregulated expression of antiapoptotic genes.In the animal model,transplanted UC-MSCs migrated toward the cerebral lesion site and decreased the lesion extent in HIE.TUNEL staining showed that the MSC group exhibited significantly reduced numbers of TUNEL-positive cells.RT-PCR and ELISA showed that UC-MSCs inhibited the upregulation of TNF-α and IL-1β in response to hypoxic ischemic injury.Conclusion These results indicate that UC-MSCs exert neuroprotective effects against hypoxic ischemic injury by inhibiting apoptosis,and the mechanism appears to be through alleviating the inflammatory response.