Khanteymoori Alireza, Peterson Clayton, Atamny Roza, Hohenhaus Marc, Beck Jürgen, Howells David W, Schwab Jan M, Watzlawick Ralf
Department of Neurosurgery, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.
College of Arts and Science, The Ohio State University, Columbus, OH, USA.
Neurorehabil Neural Repair. 2025 Apr;39(4):312-320. doi: 10.1177/15459683241311337. Epub 2025 Jan 7.
Spinal cord injury (SCI) can impair motor, sensory, and autonomic function. The formation of the glial scar comprises protective as well as inhibitory neurite outgrowth properties operated by the deposition of chondroitin sulfate proteoglycans (CSPG). Chondroitinase ABC (ChABC) can degrade CSPG and foster neuroaxonal plasticity as a therapeutic approach to restore locomotor function after SCI.
To systematically review experimental ChABC treatments after SCI and assess their efficacy for locomotor function a comprehensive literature search was conducted following pre-registered Prospero Study protocol, selecting animal studies evaluating neurobehavioral outcomes after traumatic SCI followed by the calculation of normalized effect sizes applying meta-analysis and meta-regression methodology. Additional analyses were performed to investigate the impact of animal type, strain, sex, sample size, injury models, level of injury, and treatment duration.
Within the overall analysis of 1066 animals, a considerable amount of heterogeneity was observed. A subgroup analysis comprising experiments applying the same neurobehavioral measurement (blood-brain barrier/Basso-Mouse-Scale [BMS]-subgroup) demonstrated a 15.9% (95% CI = 11.3%-20.6%) improvement in locomotor outcomes. Different experimental characteristics influenced neurological recovery, including sex, level of injury, used anesthetic, reported dosage of ChABC treatment, the timepoint of assessment and perioperative temperature control. Sensitivity analysis applying Trim and Fill identified 19 hypothetical missing experiments suggestive of reporting bias.
Reporting bias in experimental SCI research is prevalent and not limited to a specific intervention. ChABC treatment can exert beneficial effects on locomotor recovery after SCI.
脊髓损伤（SCI）会损害运动、感觉和自主神经功能。胶质瘢痕的形成具有保护和抑制神经突生长的特性，这是由硫酸软骨素蛋白聚糖（CSPG）的沉积所介导的。软骨素酶ABC（ChABC）可以降解CSPG，并促进神经轴突可塑性，作为SCI后恢复运动功能的一种治疗方法。
为了系统评价SCI后ChABC的实验性治疗及其对运动功能的疗效，我们按照预先注册的Prospero研究方案进行了全面的文献检索，选择评估创伤性SCI后神经行为结果的动物研究，然后应用荟萃分析和荟萃回归方法计算标准化效应量。还进行了额外的分析，以研究动物类型、品系、性别、样本量、损伤模型、损伤水平和治疗持续时间的影响。
在对1066只动物的总体分析中，观察到了相当程度的异质性。一项包括应用相同神经行为测量方法的实验的亚组分析（血脑屏障/巴索小鼠量表[BMS]亚组）显示，运动结果有15.9%（95%CI=11.3%-20.6%）的改善。不同的实验特征影响神经恢复，包括性别、损伤水平、所用麻醉剂、报道的ChABC治疗剂量、评估时间点和围手术期温度控制。应用Trim和Fill的敏感性分析确定了19个假设的缺失实验，提示存在报告偏倚。
实验性SCI研究中的报告偏倚普遍存在，且不限于特定干预措施。ChABC治疗对SCI后的运动恢复可产生有益影响。
