缺氧缺血性脑损伤（HIBD）是引起新生儿死亡及幸存者长期神经功能缺陷的重要原因。骨髓间充质干细胞(BMSCs)来源的外泌体具有的神经保护作用为改善HIBD神经功能提供了新思路。我们曾报道H2S预处理的BMSCs移植于缺血再灌注模型后可显著减轻脑损伤，而H2S在HIBD新生小鼠中也有显著的神经保护作用，但其作用是否依赖BMSCs尚不清楚。我们最新研究发现BMSCs外泌体主要靶向至HIBD新生小鼠受损脑区神经元，而H2S预处理的BMSCs外泌体更能显著抑制神经元凋亡和炎症反应，促进突触重塑，从而发挥更强的神经保护作用。进一步对H2S预处理的BMSCs外泌体进行miRNA测序后发现miR-9/TN-C轴可能起关键作用。本课题拟通过体外实验联合神经元条件敲除TN-C小鼠模型，全面阐明H2S诱导的BMSCs外泌体对HIBD后的神经保护作用及机制，为研发H2S改良外泌体治疗HIBD的策略提供重要支持。

Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of mortality and neurological disabilities in infants and young children. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes have been reported as a promising target in HIBD therapy. Our previous work has demonstrated that H2S-preconditioned BMSCs could enhance the therapeutic effects of BMSCs on neuronal injury and neurological recovery. Moreover, H2S also exerted neuroprotective roles in HIBD. However, the role of H2S-preconditioned BMSCs on neonatal HIBD remains unknown. Recently, we found that exosomes derived from BMSCs mainly targeted to the neurons in lesioned hemisphere in HIBD mice. Exosomes derived from H2S-preconditioned BMSCs achieved more powerful effects in alleviating brain injury following HIBD in mice. Based on the next-generation sequencing analysis, we hypothesize that these effects are more likely to rely on microRNA(miRNA) system delivered by the H2S-triggered exosome from BMSCs, which suppresses neuronal apoptosis and neuroinflammation, promotes synaptic remodeling. This research gives a priority to miR-9, one that was significantly upregulated in BMSCs-derived exosome after H2S stimuli. We are to demonstrate miR-9 and its promising target tenascin-c (TN-C) neuroprotective unit in HIBD in vivo and vitro and clarify the mechanism via neuronal conditional TN-C deficient mice. This project is to present new stubborn evidence to enrich clinical treatment to HIBD.