Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Department of Anatomy, School of Medicine, Sun Yat-sen University, Shenzhen 518100, China.
Cells. 2021 Jun 28;10(7):1614. doi: 10.3390/cells10071614.
Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats ( = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 ( = 4) and a selective inhibitor of nNOS, 7-nitroindazole ( = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.
臂丛神经根撕脱导致上肢瘫痪。短期神经保护治疗已在模型动物中报告了运动神经元的保护和功能，但长期治疗益处的报道很少，尤其是形态学后遗症。这项形态学研究调查了 c-Jun 和神经元型一氧化氮合酶 (nNOS) 的长期抑制（神经保护治疗一个月）对臂丛神经根撕脱后 6 个月时运动神经元存活、下运动神经元超微结构特征和前肢功能的影响。与 vehicle 处理组相比，神经保护治疗在 28 天治疗期末减轻了氧化应激并保留了腹角运动神经元。在该时间点，运动神经元的保留与 c-Jun、nNOS 和促凋亡蛋白 Bim 和半胱天冬酶的抑制有关。在 6 个月的存活后，中性红染色显示，在 vehicle 处理组的大鼠中，撕脱的 C6、7 和 8 颈椎节段的大多数运动神经元和腹角萎缩（n = 4）。然而，接受神经保护治疗的大鼠（c-Jun JNK 抑制剂 SP600125，n = 4 和 nNOS 的选择性抑制剂 7-硝基吲唑，n = 4）在同侧撕脱侧保留了超过一半的运动神经元。与完整的对侧腹角或神经保护治疗组相比，撕脱的腹角中的髓鞘轴突较小但数量较多。在神经保护治疗组中，大直径轴突周围的髓鞘厚度得以保留。超微结构评估还证实，与 vehicle 对照组相比，两组神经保护治疗后细胞器包括线粒体和突触得以保留。此外，前肢功能评估表明，神经保护治疗改善了大鼠的功能能力。总之，旨在抑制退行性 c-Jun 和 nNOS 的神经保护治疗减轻了细胞凋亡，长期保留了运动神经元及其细胞器、腹角大小和前肢功能。
