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  4. Combining Peripheral Nerve Grafts and Chondroitinase Promotes Functional Axonal Regeneration in the Chronically Injured Spinal Cord

Combining Peripheral Nerve Grafts and Chondroitinase Promotes Functional Axonal Regeneration in the Chronically Injured Spinal Cord

The Journal of Neuroscience, 2009 · DOI: 10.1523/JNEUROSCI.3641-09.2009 · Published: November 25, 2009

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

This study investigates a potential treatment for chronic spinal cord injuries, where long-injured axons struggle to regrow due to their limited growth potential and the presence of inhibitory molecules in the glial scar. The researchers combined peripheral nerve grafts (PNGs) with chondroitinase ABC (ChABC) treatment to break down these inhibitory molecules, along with GDNF stimulation. The study found that this combination facilitated axons to exit the PNG into host tissue and promoted some functional recovery, suggesting a promising approach for treating chronic spinal cord injuries.

Study Duration
8 weeks after the unilateral cervical injury, 8 weeks after grafting
Participants
Adult female Sprague Dawley rats
Evidence Level
Not specified

Key Findings

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    ChABC treatment digests CSPGs within a chronic scar, which promotes behavioral recovery after chronic SCI.
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    ChABC treatment of a chronic contusion site allows regenerating axons to extend beyond a peripheral nerve graft spanning the cavity.
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    Electrical stimulation of a peripheral nerve graft bridge induces c-Fos expression in host spinal cord, which is indicative of synaptic contact by regenerating fibers.

Research Summary

This study demonstrates that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons. The researchers combined grafting of a peripheral nerve into a chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. Unlike GDNF–PBS treatment, GDNF–ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery.

Practical Implications

Therapeutic Potential

The combination of PNGs and ChABC holds promise as a therapeutic strategy for chronic spinal cord injuries, where traditional treatments are often ineffective.

Functional Recovery

The study's findings suggest that this approach can promote some degree of functional recovery, potentially improving the quality of life for individuals with chronic SCI.

Targeted Synaptic Connections

Electrical stimulation of the nerve graft resulted in c-Fos expression, indicating the formation of functional synapses and integration of regenerated axons into host circuitry.

Study Limitations

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