Vascular Endothelial Cell-derived Exosomes Protect Neural Stem Cells Against Ischemia/reperfusion Injury
Vascular Endothelial Cell-derived Exosomes Protect Neural Stem Cells Against Ischemia/reperfusion Injury
复制标题
血管内皮细胞来源的外泌体保护神经干细胞免受缺血/再灌注损伤
DOI：
10.1016/j.neuroscience.2020.05.046
复制
发表时间：
2020-08-10
期刊：
影响因子：
3.3
通讯作者：
Xu，Dongsheng
中科院分区：
文献类型：
--
作者：
Zhou，Shaoting;Gao，Beiyao;Xu，Dongsheng
急性缺血性脑损伤时血管内皮细胞被激活，神经祖细胞增殖和迁移。然而，其机制尚不清楚。在当前的研究中，我们探讨了血管内皮细胞是否促进神经祖细胞增殖以及迁移是否通过外泌体通讯发生。制备急性大脑中动脉闭塞（MCAO）模型，从bEnd中分离外泌体。3个细胞进行超离心。外泌体注射组（Exos）和PBS注射组（对照组）分别在MCAO术后2 h向大鼠脑室内注射外泌体或PBS。假手术组大鼠接受相同手术，但未造成大脑中动脉闭塞。MRI显示缺血脑损伤后第21天梗死面积减小，注射外泌体后第7、14、21天神经行为预后较对照组明显改善（p< 0.05）。MCAO后第21天安乐死，免疫荧光法检测BrdU/巢蛋白阳性细胞数。与对照组相比，Exos组大鼠梗死周围区、海马同侧DG区、SVZ腹侧亚区BrdU/巢蛋白阳性细胞显著增加（p< 0.05）。此外，体外研究表明，外泌体处理后神经祖细胞增殖和迁移被激活，细胞凋亡与对照组相比减少（p< 0.05）。我们的研究表明，外泌体在急性缺血性脑损伤的神经血管单位重建和脑保护中是必不可少的。
Vascular endothelial cells were activated during acute ischemic brain injury, which could induce neural progenitor cell proliferation and migration. However, the mechanism was still unknown. In the current study, we explored whether vascular endothelial cells promoted neural progenitor cell proliferation and whether migration occurs via exosome communication. The acute middle cerebral artery occlusion (MCAO) model was prepared, and exosomes were isolated from bEnd.3 cells by ultracentrifugation. In the exosome injection (Exos) group and PBS injection (control) group, exosomes or PBS were injected intraventricularly into rats’ brains 2 h after MCAO surgery, respectively. Sham group rats received the same surgical but did not cause middle cerebral artery occlusion. The infarct volume was reduced on day 21 after ischemic brain injury by MRI, and neurobehavioral outcomes were improved on day 7, 14, and 21 by exosome injection compared with the control (p< 0.05). On the 21st day after MCAO, the animals were euthanized, and the number of BrdU/nestin-positive cells was measured by immunofluorescence. BrdU/nestin-positive cells in Exos group rats were significantly increased (p< 0.05) in the peri infarct area, the ipsilateral DG zone of the hippocampus, and the ventral sub-regions of SVZ when compared with the rats in the control group. Further, in vitro study demonstrated that neural progenitor cell proliferation and migration were activated after exosomes treatment, and cell apoptosis was attenuated compared to the control (p< 0.05). Our study suggested that exosomes should be essential for the reconstruction of neuronal vascular units and brain protection in an acute ischemic injured brain.