Ding Yuetong, Qu Yibo, Feng Jia, Wang Meizhi, Han Qi, So Kwok-Fai, Wu Wutian, Zhou Libing
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, P.R. China; Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, P.R. China.
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, P.R. China; Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, P.R. China; Department of Anatomy LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, P.R. China.
PLoS One. 2014 Jul 8;9(7):e101918. doi: 10.1371/journal.pone.0101918. eCollection 2014.
Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5-C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.
臂丛神经损伤（BPI）和实验性脊髓神经根撕脱会导致受影响节段的运动功能丧失。神经根撕脱后，通过重新植入撕脱的神经根可显著恢复运动神经元功能。这种功能恢复在多大程度上依赖于皮质脊髓输入尚不清楚。在此，我们使用Celsr3|Emx1小鼠研究了这个问题，在这种小鼠中，皮质脊髓束（CST）在基因上缺失。在成年小鼠中，我们撕脱右侧C5 - C7运动和感觉神经根，并重新植入右侧C6神经根。行为学研究表明，与对照组相比，Celsr3|Emx1小鼠的肘部屈曲恢复受损。手术后五个月，与对照小鼠相比，在突变小鼠中观察到小轴突数量减少，髓鞘内外径的G比值更高。在手术后早期，突变小鼠脊髓中GAP - 43的表达以及外周神经中髓鞘碱性蛋白（MBP）的表达均低于对照动物。五个月后，与对照组相比，突变动物右侧肱二头肌萎缩，新形成的神经肌肉接头（NMJ）较少，肌电图（EMG）中的峰峰值幅度降低。然而，非常出乎意料的是，在突变小鼠中发现运动神经元存活率高于对照小鼠。因此，在神经根撕脱/重新植入后，CST的缺失可能是阻碍轴突再生和髓鞘再生以及靶标重新支配和新NMJ形成的重要原因，导致功能恢复较低，同时促进运动神经元存活。这些结果表明，操纵皮质脊髓传递可能有助于改善BPI后的功能恢复。
