Astrocyte-derived exosomes carry microRNA-17-5p to protect neonatal rats from hypoxic-ischemic brain damage via inhibiting BNIP-2 expression

Exosomes play critical roles in neurogenesis. This study aims to explore the mechanism of astrocyte-derived exosomes in neonatal rats with hypoxic-ischemic brain damage (HIBD). Astrocytes were collected and astrocyte-derived exosomes were isolated and identified. Neonatal rats were pre-treated with exosomes and then subjected to HIBD induction. Then the neurobehaviors, neuronal apoptosis, inflammation and oxidative stress in rat brain were measured. Differentially expressed microRNAs (miRNAs) in rat brain before and after HI procedure were analyzed. H19-7 cells were subjected to oxygen and glucose deprivation (OGD) for in vitro studies. Target relation between miR-17-5p and BNIP2 was identified. Gain- and loss-of functions of miR-17-5p and BNIP2 were conducted to identify their roles in viability, apoptosis, oxidative stress and inflammation of OGDtreated cells. Collectively, astrocyte-derived exosomes improved neurobehaviors, and reduced cerebral infarction, neuronal apoptosis, oxidative and inflammation in vivo and in vitro. The exosomes carried miR-17-5p bound to BNIP2 and negatively regulated BNIP2 expression in OGD-treated cells. Over-expression of miR-17-5p increased viability, and decreased OGD-induced apoptosis, oxidative stress and inflammation of H19-7 cells, which were reversed by over-expression of BNIP2. Taken together, the study suggested that astrocyte-derived exosomes could carry miR-17-5p to protect neonatal rats from HIBD via inhibiting BNIP-2 expression.