Erb D E, Mora R J, Bunge R P
Department of Neurological Surgery, University of Miami School of Medicine, Florida 33136.
Exp Neurol. 1993 Dec;124(2):372-6. doi: 10.1006/exnr.1993.1208.
In some cases of spinal cord injury and in certain motoneuron diseases, such as amyotrophic lateral sclerosis and spinal muscular atrophies, lower motoneurons are destroyed and muscle function cannot be restored except by reinnervation from alternate motoneuron sources. We have tested the feasibility of employing local transplantation of embryonic motoneurons to restore innervation to denervated somatic muscle as a first step in salvaging muscle function and enabling use of functional electric stimulation. Dissociated ventral spinal cord cells from Embryonic Days 14 and 15 rats were transplanted into the distal stump of axotomized tibial nerves of adult rats. Animals were killed 3-18 weeks after transplantation. After 3 weeks large multipolar cells, resembling alpha motoneurons, were observed within the transplant site surrounded by myelinated and unmyelinated axons and dendrites. Axons emanating from these transplanted motoneurons were identified within the nerve stump and within the previously denervated gastrocnemius muscle, forming neuromuscular junctions. Transplanted motoneurons survived up to 18 weeks and were labeled after intramuscular injection of fast blue. This study demonstrates that embryonic spinal motoneurons, transplanted into the distal adult peripheral nerve stump, are able to survive and reinnervate the denervated target muscle. We are now exploring the possibility of using this experimental approach to retard the atrophy of denervated skeletal muscle, thus providing a muscle capable of useful response to functional electrical stimulation.
在某些脊髓损伤病例以及某些运动神经元疾病中，如肌萎缩侧索硬化症和脊髓性肌萎缩症，下运动神经元被破坏，除非通过其他运动神经元来源进行重新支配，否则肌肉功能无法恢复。我们测试了采用胚胎运动神经元局部移植来恢复去神经支配的躯体肌肉的神经支配的可行性，作为挽救肌肉功能并实现功能性电刺激应用的第一步。将来自胚胎第14天和15天大鼠的解离的腹侧脊髓细胞移植到成年大鼠经轴突切断的胫神经的远端残端。在移植后3 - 18周处死动物。3周后，在移植部位观察到大型多极细胞，类似于α运动神经元，周围有髓鞘和无髓鞘的轴突及树突。从这些移植的运动神经元发出的轴突在神经残端和先前去神经支配的腓肠肌内被识别出来，形成神经肌肉接头。移植的运动神经元存活长达18周，并在肌肉内注射快蓝后被标记。这项研究表明，移植到成年外周神经远端残端的胚胎脊髓运动神经元能够存活并重新支配去神经支配的靶肌肉。我们现在正在探索使用这种实验方法来延缓去神经支配的骨骼肌萎缩的可能性，从而提供一种能够对功能性电刺激产生有效反应的肌肉。
