Intraspinal microinjection of chondroitinase ABC following injury promotes axonal regeneration out of a peripheral nerve graft bridge

Exp Neurol, 2008 · DOI: 10.1016/j.expneurol.2008.01.021 · Published: May 1, 2008

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Following a spinal cord injury, a glial scar forms which inhibits axonal regeneration. This scar contains chondroitin sulfate proteoglycans (CSPGs), which are inhibitory molecules. The enzyme chondroitinase ABC (ChABC) can digest these CSPGs. This study explores a new method of delivering ChABC, directly injecting it into the injury site to overcome the limitations of using osmotic minipumps, a method that has technical challenges. The researchers found that injecting ChABC allowed more axons to regenerate out of a peripheral nerve graft and back into the spinal cord tissue, suggesting this method is effective for delivering the enzyme.

Study Duration

3 weeks

Participants

Adult female Sprague-Dawley rats (225-250g)

Evidence Level

Not specified

Key Findings

1
Microinjection of ChABC resulted in extensive CSPG digestion around the injury site.
2
The microinjection technique did not cause a noticeable inflammatory response in the spinal cord tissue.
3
Microinjection of ChABC permitted significantly more regenerating axons to exit a PNG and re-enter spinal cord tissue compared to saline injections.

Research Summary

This study investigated the efficacy of microinjecting ChABC directly into the injury site in a rat model of spinal cord injury, using a peripheral nerve graft (PNG) to bridge the injury. The results showed that microinjection of ChABC effectively digested CSPGs, did not induce a significant inflammatory response, and promoted axonal regeneration out of the PNG and into the spinal cord. The authors conclude that microinjection of ChABC is an effective alternative to osmotic minipumps for delivering the enzyme to promote axonal regeneration after spinal cord injury.

Practical Implications

Improved Delivery Method

Microinjection of ChABC offers a technically simpler and potentially more effective method for delivering the enzyme to the injury site compared to osmotic minipumps.

Therapeutic Potential

The study supports the therapeutic potential of ChABC in promoting axonal regeneration and functional recovery after spinal cord injury.

Reduced Inflammation

The microinjection technique minimizes inflammation, which is crucial for creating a favorable environment for axonal regeneration.

Study Limitations

1
The study did not test the ChABC-treated animals behaviorally to determine definitively that these axons do mediate functional recovery.
2
There is debate about whether ChABC that is stored within the pump at body temperature remains biologically active over a 5-day infusion period
3
The enzyme was likely diluted by cerebrospinal fluid, so the final active concentration that penetrated the injury site is unknown.

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