Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection

PLoS ONE, 2015 · DOI: 10.1371/journal.pone.0138705 · Published: September 22, 2015

Spinal Cord Injury Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates a treatment for spinal cord injury (SCI) using an enzyme called chondroitinase ABC (ChABC). ChABC can digest molecules that inhibit nerve regeneration. The researchers found that delivering a high dose of ChABC directly into the injured spinal cord during the sub-acute phase (after the initial injury) helped to reduce scar tissue and promote the growth of nerve fibers. This treatment also led to improved locomotor recovery in rats with complete spinal cord transection, suggesting it could be a promising approach for treating SCI in humans.

Study Duration

10 weeks

Participants

58 young adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Intraparenchymal injection of high-dose ChABC in sub-acute SCI does not induce subarachnoid hemorrhage.
2
High-dose ChABC treatment prevented the shrinking of spinal cord stumps and decreased the extent and area of the lesion as well as cyst formation.
3
Treatment with high-dose chondroitinase ABC in the sub-acute stage promoted axonal regeneration to the function-related nuclei in the brain stem.

Research Summary

This study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. The intraparenchymal high-dose ChABC treatment significantly digested the CSPGs, decreased the extent and area of the lesion and decreased cyst formation. These protective effects preserved the spinal cord tissue, enhanced axon outgrowth throughout the injury site, and significantly improved functional recovery in the complete spinal cord transection model. The application of high-dose ChABC in the sub-acute stage of SCI can promote long-lasting digestion of CSPGs in the lesion site, decrease the extent and area of the lesion and decrease cyst formation in the spinal cord tissue.

Practical Implications

Clinical Translation

The study suggests that high-dose ChABC treatment in the sub-acute stage of SCI could be important for future clinical translation of ChABC therapy for spinal cord injury.

Combination Therapies

The research indicates that combining ChABC with other therapeutic strategies, such as neuronal growth factors and cellular transplantation, is necessary for promoting functional plasticity of sprouting axons after sub-acute SCI.

Locomotor Recovery

The findings demonstrate that high-dose ChABC treatment significantly promoted axonal regrowth and partial functional locomotor recovery in the sub-acute stage of severe SCI.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
Only slight movements of the ankle, knee, and hip were exhibited after treatment, suggesting that the functional reconnections were not completely established.
3
The study notes that a single administration of ChABC may not be sufficient to promote functional plasticity following severe SCI and that multifactor strategies may be needed.

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