Department of Cell Biology and Neurobiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, PR China; Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, PR China.
Department of Cell Biology and Neurobiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, PR China.
Brain Res. 2020 Jun 15;1737:146802. doi: 10.1016/j.brainres.2020.146802. Epub 2020 Mar 24.
Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, regulates various biological processes in mammals. The effect of GDF11 in brain injury has not been fully elucidated. Our aim was to investigate the effects of GDF11 in cerebral ischemic injury. The expression level of GDF11 increased significantly in the peri-infarct cerebral cortex. Next, the effect of the intracerebroventricular injection of a GDF11 overexpression lentivirus or rGDF11 was investigated in middle cerebral artery occlusion (MCAO) rats. The preventative effects of the GDF11 overexpression virus on stroke were observed. The delivery of the lentivirus into rats before MCAO significantly reduced the infarct volume and the percentage of apoptotic cells and improved motor function in MCAO rats. Furthermore, it elevated the expression of p-Smad2/3 and promoted neurogenesis and angiogenesis in the ipsilateral SVZ during ischemic injury. More importantly, the therapeutic effects of rGDF11 on stroke were subsequently explored. The results in MCAO rats treated with rGDF11 were found similar to that in those treated with the GDF11 overexpression lentivirus. Together, these findings indicate that GDF11 has neuroprotective and neurorestorative effects in cerebral ischemic injury and provide new insights into the function and mechanism of GDF11 in stroke models.
生长分化因子 11（GDF11）是转化生长因子-β（TGF-β）超家族的成员，调节哺乳动物中的各种生物学过程。GDF11 在脑损伤中的作用尚未完全阐明。我们的目的是研究 GDF11 在脑缺血损伤中的作用。GDF11 的表达水平在梗死周边皮质中显著增加。接下来，我们研究了 GDF11 过表达慢病毒或 rGDF11 脑室内注射对大脑中动脉闭塞（MCAO）大鼠的影响。观察 GDF11 过表达病毒对中风的预防作用。MCAO 前将慢病毒递送至大鼠体内可显著减小梗死体积和凋亡细胞比例，并改善 MCAO 大鼠的运动功能。此外，它还可提高 p-Smad2/3 的表达，促进缺血性损伤时同侧 SVZ 中的神经发生和血管生成。更重要的是，我们随后探讨了 rGDF11 对中风的治疗效果。结果发现，MCAO 大鼠接受 rGDF11 治疗后的效果与接受 GDF11 过表达慢病毒治疗后的效果相似。总之，这些发现表明 GDF11 在脑缺血损伤中具有神经保护和神经修复作用，并为 GDF11 在中风模型中的功能和机制提供了新的见解。
