Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
Extracellular vesicle-mediated transfer of miR-21-5p from mesenchymal stromal cells to neurons alleviates early brain injury to improve cognitive function via the PTEN/Akt pathway after subarachnoid hemorrhage
复制标题
DOI：
10.1038/s41419-020-2530-0
复制
发表时间：
2020-05-13
影响因子：
9
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Gao, Xiao;Xiong, Ye;Li, Gang
蛛网膜下腔出血（SAH）患者即使接受了适当的治疗（如动脉瘤夹闭或弹簧圈栓塞），也经常会出现认知功能障碍，这会导致重返工作岗位的问题，并给家庭带来负担。间充质干细胞（MSC）衍生的细胞外囊泡（MSC-EV）作为治疗中风的有前途的治疗囊泡已受到越来越多的关注。在这项研究中，我们探讨了MSC-EV在SAH大鼠模型中的潜在作用。我们观察到MSC-EV通过减少神经元凋亡来改善SAH后的早期脑损伤（EBI），并且SAH诱导了前额叶皮层和海马中miR-21表达水平的增加。此外，使用来自exRNA Atlas的miRNA分析和CSF测序数据，我们证明了EV衍生的miR-21保护神经元免于凋亡并减轻了SAH诱导的认知功能障碍。MSC-EV的神经保护作用通过miR-21敲低或给予MK2206（一种PTEN/Akt抑制剂）而消除。总之，我们的研究结果表明，MSC-EV通过将miR-21转移到受体神经元来促进SAH后神经元的存活并减少EBI。
Patients with subarachnoid hemorrhage (SAH) often suffer from cognitive function impairments even when they have received proper treatment, such as the clipping or coiling of aneurysms, and this causes problems with returning to work and burdens the family. Increasing attention has been paid to mesenchymal stem cell (MSC)-derived extracellular vesicle (MSC-EV) as promising therapeutic vesicles for stroke management. In this study, we explored the potential role of MSC-EV in a rat model of SAH. We observed that MSC-EV ameliorated early brain injury (EBI) after SAH by reducing the apoptosis of neurons and that SAH induced an increase in the expression level of miR-21 in the prefrontal cortex and hippocampus. In addition, using miRNA profiling and CSF sequencing data from the exRNA Atlas, we demonstrated that EV-derived miR-21 protected neurons from apoptosis and alleviated SAH-induced cognitive dysfunction. The neuroprotective role of MSC-EV was abrogated by miR-21 knockdown or the administration of MK2206, a PTEN/Akt inhibitor. Overall, our results suggest that MSC-EV promotes neuronal survival and alleviates EBI after SAH through transferring miR-21 to recipient neurons.