He Peibang, Zhang Hui, Wang Jianfeng, Guo Yujia, Tian Qi, Liu Chengli, Gong Pian, Ye Qingsong, Peng Youjian, Li Mingchang
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Center of Regenerative Medicine & Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Neurochem Res. 2025 Jan 30;50(2):91. doi: 10.1007/s11064-025-04340-y.
Subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke with high morbidity, mortality and disability, and early brain injury (EBI) after SAH is crucial for prognosis. Recently, stem cell therapy has garnered significant attention in the treatment of neurological diseases. Compared to other stem cells, dental pulp stem cells (DPSCs) possess several advantages, including abundant sources, absence of ethical concerns, non-invasive procurement, non-tumorigenic history and neuroprotective potential. Therefore, we aim to investigate whether DPSCs can improve EBI after SAH, and explore the mechanisms. In our study, we utilized the endovascular perforation method to establish a SAH mouse model and investigated whether DPSCs administered via tail vein injection could improve EBI after SAH. Furthermore, we used hemin-stimulated HT22 cells to simulate neuronal cell injury induced by SAH and employed a co-culture approach to examine the effects of DPSCs on these cells. To gain insights into the potential mechanisms underlying the improvement of SAH-induced EBI by DPSCs, we conducted bioinformatics analysis. Finally, we further validated our findings through experiments. In vivo experiments, we found that DPSCs administration improved neurological dysfunction, reduced brain edema, and prevented neuronal apoptosis in SAH mice. Additionally, we observed a decrease in the expression level of miR-26a-5p in the cortical tissues of SAH mice, which was significantly increased following intravenous injection of DPSCs. Through bioinformatic analysis and luciferase reporter assay, we confirmed the target relationship between miR-26a-5p and PTEN. Moreover, we demonstrated that DPSCs exerted neuroprotective effects by modulating the miR-26a-5p/PTEN/AKT pathway. Our study demonstrates that DPSCs can improve EBI after SAH through the miR-26a-5p/PTEN/AKT pathway, laying a foundation for the application of DPSCs in SAH treatment. These findings provide a theoretical basis for further investigating the therapeutic mechanisms of DPSCs and developing novel treatment strategies in SAH.
蛛网膜下腔出血（SAH）是一种具有高发病率、死亡率和致残率的出血性中风，SAH后的早期脑损伤（EBI）对预后至关重要。近年来，干细胞疗法在神经系统疾病的治疗中备受关注。与其他干细胞相比，牙髓干细胞（DPSC）具有多种优势，包括来源丰富、不存在伦理问题、获取方式无创、无致瘤史以及具有神经保护潜力。因此，我们旨在研究DPSC是否能改善SAH后的EBI，并探索其机制。在我们的研究中，我们采用血管内穿刺法建立SAH小鼠模型，研究经尾静脉注射给予DPSC是否能改善SAH后的EBI。此外，我们使用氯化血红素刺激的HT22细胞模拟SAH诱导的神经元细胞损伤，并采用共培养方法研究DPSC对这些细胞的影响。为了深入了解DPSC改善SAH诱导的EBI的潜在机制，我们进行了生物信息学分析。最后，我们通过实验进一步验证了我们的发现。在体内实验中，我们发现给予DPSC可改善SAH小鼠的神经功能障碍，减轻脑水肿，并防止神经元凋亡。此外，我们观察到SAH小鼠皮质组织中miR-26a-5p的表达水平降低，静脉注射DPSC后该水平显著升高。通过生物信息学分析和荧光素酶报告基因检测，我们证实了miR-26a-5p与PTEN之间的靶向关系。此外，我们证明DPSC通过调节miR-26a-5p/PTEN/AKT通路发挥神经保护作用。我们的研究表明，DPSC可通过miR-26a-5p/PTEN/AKT通路改善SAH后的EBI，为DPSC在SAH治疗中的应用奠定了基础。这些发现为进一步研究DPSC的治疗机制和开发SAH的新型治疗策略提供了理论依据。
