School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
State Key Laboratory of Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
J Neuropathol Exp Neurol. 2018 Apr 1;77(4):325-343. doi: 10.1093/jnen/nly009.
When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation. Application of exogenous GDNF to injured spinal cord greatly prevented the motoneuron death and enhanced the regeneration and axonal sprouting, whereas no effect was seen on the functional recovery. In contrast, cell transplantation into the distal nerve did not affect the host motoneurons but instead mitigated the muscle atrophy. The combination of GDNF and cell graft reunited the positive effects resulting in better functional recovery and could therefore be considered as a promising strategy for nerve and spinal cord injuries that involve the avulsion of spinal roots.
当脊髓神经根从脊髓撕裂时，外周和中枢神经系统都会受到损伤。由于运动神经元失去轴突，它们开始迅速死亡，而靶肌肉由于去神经支配而萎缩。在这种复杂的损伤中，需要针对不同的过程来寻找最佳的治疗策略。在这项研究中，我们测试了胶质细胞衍生的神经营养因子（GDNF）治疗和胎儿腰椎细胞移植，以防止脊髓根撕脱和延迟再植入后运动神经元死亡和肌肉萎缩。将外源性 GDNF 应用于受伤的脊髓可以大大防止运动神经元死亡，并增强再生和轴突发芽，但对功能恢复没有影响。相比之下，细胞移植到远端神经不会影响宿主运动神经元，而是减轻肌肉萎缩。GDNF 和细胞移植物的联合应用汇集了积极的效果，导致更好的功能恢复，因此可以被认为是一种有前途的策略，用于涉及神经根撕脱的神经和脊髓损伤。
