The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
J Neurotrauma. 2013 Jun 15;30(12):1062-9. doi: 10.1089/neu.2012.2797.
Few options exist for treatment of pervasive motoneuron death after spinal cord injury or in neurodegenerative diseases such as amyotrophic lateral sclerosis. Local transplantation of embryonic motoneurons into an axotomized peripheral nerve is a promising approach to arrest the atrophy of denervated muscles; however, muscle reinnervation is limited by poor motoneuron survival. The aim of the present study was to test whether acute electrical stimulation of transplanted embryonic neurons promotes motoneuron survival, axon growth, and muscle reinnervation. The sciatic nerve of adult Fischer rats was transected to mimic the widespread denervation seen after disease or injury. Acutely dissociated rat embryonic ventral spinal cord cells were transplanted into the distal tibial nerve stump as a neuron source for muscle reinnervation. Immediately post-transplantation, the cells were stimulated at 20 Hz for 1 h. Other groups were used to control for the cell transplantation and stimulation. When neurons were stimulated acutely, there were significantly more neurons, including cholinergic neurons, 10 weeks after transplantation. This led to enhanced numbers of myelinated axons, reinnervation of more muscle fibers, and more medial and lateral gastrocnemius muscles were functionally connected to the transplant. Reinnervation reduced muscle atrophy significantly. These data support the concept that electrical stimulation rescues transplanted motoneurons and facilitates muscle reinnervation.
脊髓损伤或肌萎缩性侧索硬化等神经退行性疾病发生广泛性运动神经元死亡后，治疗选择有限。将胚胎运动神经元局部移植到切断的周围神经中是阻止去神经肌肉萎缩的一种很有前途的方法；然而，运动神经元存活不良限制了肌肉再神经支配。本研究旨在测试急性电刺激移植的胚胎神经元是否促进运动神经元存活、轴突生长和肌肉再神经支配。成年 Fischer 大鼠的坐骨神经被切断，以模拟疾病或损伤后广泛的去神经支配。急性分离的大鼠胚胎脊髓腹侧细胞被移植到远端胫骨神经残端，作为肌肉再神经支配的神经元来源。移植后立即以 20 Hz 刺激 1 小时。其他组用于控制细胞移植和刺激。当神经元被急性刺激时，10 周后移植后有明显更多的神经元，包括胆碱能神经元。这导致更多有髓轴突的数量增加，更多的肌纤维被再神经支配，更多的内侧和外侧比目鱼肌与移植物功能连接。再神经支配显著减少了肌肉萎缩。这些数据支持电刺激拯救移植的运动神经元并促进肌肉再神经支配的概念。
