Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Int J Mol Sci. 2021 Apr 29;22(9):4746. doi: 10.3390/ijms22094746.
Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.
周围压迫性神经病会引起明显的神经病理性疼痛、肌肉无力和延长的神经炎症。手术减压仍然是治疗的金标准,但效果并不理想,复发率很高。从机械压迫到局部炎症信号的化学传播,人们对神经减压后的不同神经病理模式和遗传特征知之甚少。在这项研究中,对大鼠坐骨神经施加可控的机械压缩力会导致不可逆转的感觉运动功能障碍,并持续局部神经炎症,即使在神经释放后 4 周也是如此。在背根神经节中发现了显著的基因上调,涉及炎症、促凋亡和神经病理性疼痛信号。局部损伤神经的神经炎症基因谱分析显示,神经释放后,涉及氧化固醇代谢、神经元凋亡和增殖的多个基因持续上调。进一步验证每个信号通路的独立作用将有助于未来对压迫性神经病的分子治疗。