Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments.
Inhibition of the Nogo-pathway in experimental spinal cord injury: a meta-analysis of 76 experimental treatments.
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DOI：
10.1038/s41598-023-49260-5
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发表时间：
2023-12-21
影响因子：
4.6
通讯作者：
Watzlawick, Ralf
中科院分区：
文献类型：
--
作者：
Hirt, Julian;Khanteymoori, Alireza;Hohenhaus, Marc;Kopp, Marcel A.;Howells, David W.;Schwab, Jan M.;Watzlawick, Ralf
脊髓损伤（SCI）后的恢复可以通过可塑性增强治疗来促进。髓磷脂相关神经生长抑制剂 Nogo-A (Reticulon 4, RTN4) 通路已被证明可以限制实验性 SCI 模型中的神经轴突可塑性。早期随机对照试验正在进行中，以研究 Nogo-A/Nogo-受体 (NgR1) 通路阻断剂的作用。这项对阻断 Nogo-A 通路的治疗方法的系统回顾和荟萃分析根据预先注册的研究方案探讨了实验性 SCI 后功能性运动恢复的功效。共有 51 份手稿报告了 1572 只动物的 76 项实验，经鉴定用于荟萃分析。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 个实验，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组规模与较大的效应大小相关。延迟治疗开始与较低的效应大小相关。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导致效应大小减小[8.8% (95% CI 2.6–14.9)]。现有数据表明，在动物研究中，Nogo-A/NgR1 通路的抑制会改变 SCI 后的功能恢复，尽管所应用的损伤机制和其他研究细节存在显着差异。镜像早期评估的其他 SCI 干预措施，我们确定了与结果异质性相关的类似因素。
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.
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