Department of Neurology and Experimental Neurology, Charité Campus Mitte, Clinical and Experimental Spinal Cord Injury Research Laboratory (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Straße 64, 79106, Freiburg, Germany.
Sci Rep. 2023 Dec 21;13(1):22898. doi: 10.1038/s41598-023-49260-5.
Recovery after spinal cord injury (SCI) may be propagated by plasticity-enhancing treatments. The myelin-associated nerve outgrowth inhibitor Nogo-A (Reticulon 4, RTN4) pathway has been shown to restrict neuroaxonal plasticity in experimental SCI models. Early randomized controlled trials are underway to investigate the effect of Nogo-A/Nogo-Receptor (NgR1) pathway blockers. This systematic review and meta-analysis of therapeutic approaches blocking the Nogo-A pathway interrogated the efficacy of functional locomotor recovery after experimental SCI according to a pre-registered study protocol. A total of 51 manuscripts reporting 76 experiments in 1572 animals were identified for meta-analysis. Overall, a neurobehavioral improvement by 18.9% (95% CI 14.5-23.2) was observed. Subgroup analysis (40 experiments, N = 890) revealed SCI-modelling factors associated with outcome variability. Lack of reported randomization and smaller group sizes were associated with larger effect sizes. Delayed treatment start was associated with lower effect sizes. Trim and Fill assessment as well as Egger regression suggested the presence of publication bias. Factoring in theoretically missing studies resulted in a reduced effect size [8.8% (95% CI 2.6-14.9)]. The available data indicates that inhibition of the Nogo-A/NgR1pathway alters functional recovery after SCI in animal studies although substantial differences appear for the applied injury mechanisms and other study details. Mirroring other SCI interventions assessed earlier we identify similar factors associated with outcome heterogeneity.
脊髓损伤 (SCI) 后的恢复可以通过增强可塑性的治疗来促进。髓鞘相关神经生长抑制因子 Nogo-A（Reticulon 4，RTN4）通路已被证明可限制实验性 SCI 模型中的神经轴突可塑性。目前正在进行早期随机对照试验，以研究 Nogo-A/Nogo-受体（NgR1）通路阻滞剂的效果。本系统评价和荟萃分析根据预先注册的研究方案，调查了阻断 Nogo-A 通路的治疗方法对实验性 SCI 后功能运动恢复的疗效。共确定了 51 篇报告了 1572 只动物的 76 项实验的文献进行荟萃分析。总体而言，观察到神经行为改善了 18.9%（95%CI 14.5-23.2）。亚组分析（40 项实验，N=890）揭示了与结果变异性相关的 SCI 建模因素。缺乏报告的随机化和较小的样本量与较大的效应量相关。治疗开始时间延迟与较小的效应量相关。修剪和填充评估以及 Egger 回归表明存在发表偏倚。考虑到理论上缺失的研究，效应量降低[8.8%（95%CI 2.6-14.9)]。现有数据表明，抑制 Nogo-A/NgR1 通路可改变动物研究中 SCI 后的功能恢复，但应用的损伤机制和其他研究细节存在明显差异。与我们早些时候评估的其他 SCI 干预措施一样，我们确定了与结果异质性相关的类似因素。
