Talifu Zuliyaer, Xu Xin, Du Huayong, Li Zehui, Wang Xiaoxin, Zhang Chunjia, Pan Yunzhu, Ke Han, Liu Wubo, Gao Feng, Yang Degang, Jing Yingli, Yu Yan, Du Liangjie, Li Jianjun
School of Rehabilitation, Capital Medical University, Beijing, China.
Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center, Beijing, China.
Animal Model Exp Med. 2025 Apr;8(4):595-605. doi: 10.1002/ame2.12545. Epub 2025 Jan 23.
The inability of damaged neurons to regenerate and of axons to establish new functional connections leads to permanent functional deficits after spinal cord injury (SCI). Although astrocyte reprogramming holds promise for neurorepair in various disease models, it is not sufficient on its own to achieve significant functional recovery.
A rat SCI model was established using a spinal cord impactor. Seven days postsurgery, adeno-associated virus were injected to overexpress the transcription factors NeuroD1 and Neurogenin-2 (Ngn2) in the spinal cord. The rats were then trained to walk on a weight-supported treadmill for 4 weeks, starting 14 days after modeling. The effects of these interventions on motor and sensory functions, as well as spinal cord tissue repair, were subsequently evaluated.
The combination of NeuroD1 and Ngn2 overexpression with weight-supported exercise training significantly improved gait compared to either intervention alone. The group receiving the combined intervention exhibited enhanced sensitivity in sensory assessments. Immunofluorescence analysis revealed increased colocalization of astrocytes and microtubule-associated protein 2-positive neurons in the injury area. These effects were more pronounced than those observed with spinal cord tissue repair alone. Additionally, the combined intervention significantly reduced glial scarring and the size of the injury area.
Exercise intervention enhances the reprogramming effects of astrocytes and restores motor function, yielding better results than either intervention alone.
受损神经元无法再生且轴突无法建立新的功能连接，导致脊髓损伤（SCI）后出现永久性功能缺陷。尽管星形胶质细胞重编程在各种疾病模型中有望实现神经修复，但其本身不足以实现显著的功能恢复。
使用脊髓撞击器建立大鼠SCI模型。术后7天，注射腺相关病毒以在脊髓中过表达转录因子NeuroD1和神经生成素-2（Ngn2）。然后在建模后14天开始训练大鼠在减重跑步机上行走4周。随后评估这些干预措施对运动和感觉功能以及脊髓组织修复的影响。
与单独的任何一种干预相比，NeuroD1和Ngn2过表达与减重运动训练相结合显著改善了步态。接受联合干预的组在感觉评估中表现出更高的敏感性。免疫荧光分析显示损伤区域星形胶质细胞与微管相关蛋白2阳性神经元的共定位增加。这些效果比单独的脊髓组织修复更明显。此外，联合干预显著减少了胶质瘢痕形成和损伤区域的大小。
运动干预增强了星形胶质细胞的重编程效果并恢复了运动功能，比单独的任何一种干预产生更好的结果。
