Pan Lu, Yi Lingrong, Liu Yuan, Liu Li, Zhu Ying, Zhong Juan, Wang Yunhang, Yin Ying, Yu Lehua, Tan Botao, Yang Ce
State Key Laboratory of Trauma, Burns and Combined Injury, Department of Research Institute of Surgery, The Army Medical University, Chongqing 400042, China; Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Neurosci Lett. 2023 Mar 13;800:137121. doi: 10.1016/j.neulet.2023.137121. Epub 2023 Feb 8.
Previous studies reported that the codeletion of PTEN and SOCS3 can greatly enhance the capacity of axon regeneration after central nervous system (CNS) injury. Moreover, the promotion of functional recovery can be improved by rehabilitative training under a use-dependent plasticity mechanism after CNS injury. However, few studies have reported the interaction between these mechanisms after spinal cord injury (SCI). Therefore, we investigated the combined effects of PTEN/SOCS3 coinhibition and rehabilitative training on axon regeneration and upper extremity motor functional improvement after cervical SCI in mice. In this study, we used RNA interference viruses to coinhibit PTEN and SOCS3 and induced a C5 crush injury on the side of preference. The injured upper extremity was trained by single pellet grasping for 4 weeks. We found that the coinjection of viruses significantly increased the expression of p-S6 and p-STAT in the cortex, reduced the dieback pattern of injured axons and promoted traced axon regeneration. More importantly, combination therapy further enhanced axon regeneration compared with PTEN/SOCS3 coinhibition alone. In behavioral tests, the motor performance of the mice in the PTEN/SOCS3 + Training group was better than that of the mice in the other groups. These results indicate that combining task-based rehabilitative training with PTEN/SOCS3 coinhibition further promotes axon regeneration and significant improvement in forelimb skilled motor function after cervical SCI. Our findings provide new therapeutic insights into SCI treatment.
先前的研究报道，PTEN和SOCS3的共同缺失可极大地增强中枢神经系统（CNS）损伤后轴突再生的能力。此外，在CNS损伤后，通过基于使用依赖性可塑性机制的康复训练可促进功能恢复。然而，鲜有研究报道脊髓损伤（SCI）后这些机制之间的相互作用。因此，我们研究了PTEN/SOCS3共抑制与康复训练对小鼠颈段SCI后轴突再生和上肢运动功能改善的联合作用。在本研究中，我们使用RNA干扰病毒共抑制PTEN和SOCS3，并在偏好侧诱导C5挤压损伤。对受伤的上肢进行单颗粒抓取训练4周。我们发现病毒共注射显著增加了皮质中p-S6和p-STAT的表达，减少了受损轴突的回缩模式，并促进了示踪轴突的再生。更重要的是，与单独的PTEN/SOCS3共抑制相比，联合治疗进一步增强了轴突再生。在行为测试中，PTEN/SOCS3 +训练组小鼠的运动表现优于其他组小鼠。这些结果表明，将基于任务的康复训练与PTEN/SOCS3共抑制相结合可进一步促进颈段SCI后轴突再生和前肢熟练运动功能的显著改善。我们的研究结果为SCI治疗提供了新的治疗思路。
