Targeting Nerve Fiber Outgrowth Inhibition After Experimental Spinal Cord Injury: A Systematic Review and Meta-analysis of Chondroitinase ABC

Abstract

Background: 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.

Objectives: 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.

Results: 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.

Conclusion: 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.

Keywords: ChABC; meta-analysis; spinal cord injury; systematic review.