In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable biomaterial scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axons, and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce tissue damage and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.

在哺乳动物中，脊髓损伤通常通过下运动神经元凋亡和神经肌肉接头去神经支配而导致肌肉瘫痪。先前的研究表明，脊髓损伤的炎症反应可能会在最初的创伤后导致额外的组织损伤。为了调节这种炎症反应，我们通过加载到可植入生物材料支架上，将慢病毒抗炎白细胞介素 10 递送到小鼠 C5 椎骨的左侧半切片中。我们假设与抗炎治疗相关的行为结果的改善是由于精细运动回路组件的保护。我们使用梯梁检查了行为恢复情况，使用组织学检查了组织保留，并使用脊髓内光遗传学刺激在受伤后 2 周检查了肌电图记录。阶梯束分析显示，与用对照病毒治疗的小鼠相比，白介素 10 治疗可显着改善受伤后 2 周和 12 周的行为恢复。组织学显示，受伤后 2 周，白细胞介素 10 导致下运动神经元、轴突和肌肉神经支配数量增多。此外，肌电图记录表明，受伤后 2 周时，经白细胞介素 10 处理的动物的信噪比和峰峰值幅度与未受伤对照动物的信噪比和峰峰值幅度比与受伤对照动物的信噪比和峰峰值更相似。这些数据表明，使用抗炎白细胞介素 10 进行基因治疗可以显着减少脊髓损伤后的组织损伤和随后的运动缺陷。总之，这些结果表明，早期调节损伤反应可以保护肌肉功能，并具有持久的益处。