Chondroitinase ABC Administration in Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis

Abstract

Objective: The present systematic review and meta-analysis intends to conduct a comprehensive and complete search in electronic resources to investigate the role of administrating ChABC in improving complications following SCI. Methods: Medline, Embase, Scopus and Web of sciences were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using STATA 14.0 program, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI). Results: 34 pre-clinical studies were included. ChABC administration generally improves locomotion recovery after SCI (SMD = 0.90; 95% CI: 0.61 to 1.20; p <0.001). Subgroup analysis showed that differences in SCI model (p = 0.732), severity of injury (p = 0.821), number of ChABC administration (p = 0.092), blinding status (p = 0.294), use of different locomotor score (p = 0.567) and follow up duration (p = 0.750) have no effect on the efficacy of ChABC treatment. Conclusion: The findings of the present study showed that prescribing ChABC has a moderate effect in the improvement of locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as an adjuvant therapy and not as a primary therapy.

Sustained delivery of chABC improves functional recovery after a spine injury

“…Many pre-clinical articles have examined the effects of chABC injection on the improvement of functional recovery after SCI [58][59][60][61][62]. The results of a meta-analysis showed that the enzyme chABC injected alone had a moderate effect on the functional recovery post-SCI (SMD = 0.90; 95% CI 0.61 to 1.20; p < 0.001) [40].…”

“…chABC also degrades the CSPGs that form perineuronal nets, thereby enhancing axonal sprouting and plasticity [37][38][39]. However, the use of chABC in animal models has problems that have caused the effect of chABC to be moderately reported in a metaanalysis study based on the results of 34 preclinical studies [40].…”

In Vitro Assessment of Protamine Toxicity with Neural Cells, Its Therapeutic Potential to Counter Chondroitin Sulfate Mediated Neuron Inhibition, and Its Effects on Reactive Astrocytes

“…ChABC degrades the sulfated glycosaminoglycan side chains on CSPGs and improves functional outcomes in rodent models after SCI or TBI. [17][18][19] However, very specific sulfation patterns present in CSPGs play inhibitory roles in the CNS. Specifically, the CS-A sulfation pattern is neuroinhibitory while CS-C sulfation tends to be more permissive to axonal growth.…”

Role of durotomy on function outcome, tissue sparing, inflammation, and tissue stiffness after spinal cord injury in rats

“…21,22 Following acute SCI, the first 24 h after injury are critical for achieving optimal neurological recovery with decompressive surgery. 22,23 Presently, there is ongoing debate regarding the prospective neurological benefits of durotomy. Smith et al 24 examined the recovery implications of durotomy with duroplasty in 72 rodents suffering from cervical SCI.…”

“… 21 , 22 Following acute SCI, the first 24 h after injury are critical for achieving optimal neurological recovery with decompressive surgery. 22 , 23 …”