Combining Peripheral Nerve Grafting and Matrix Modulation to Repair the Injured Rat Spinal Cord

JoVE, 2009 · DOI: 10.3791/1324 · Published: January 1, 2009

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Traumatic injury to the spinal cord (SCI) causes death of neurons, disruption of motor and sensory nerve fiber (axon) pathways and disruption of communication with the brain. To accomplish this we developed a peripheral nerve (PN) grafting technique where segments of sciatic nerve are either placed directly between the damaged ends of the spinal cord or are used to form a bridge across the lesion. Regenerated axons that reach the distal end of the PN graft often fail to extend back into the spinal cord, so we use microinjections of chondroitinase to degrade inhibitory molecules associated with the scar tissue surrounding the area of SCI.

Study Duration

Several months

Participants

Rats (also mouse and cat models mentioned)

Evidence Level

Not specified

Key Findings

1
Ascending and descending spinal axons will enter the graft, grow in a relatively straight line parallel to the length of the graft and extend to the distal end of the graft at a rate of approximately 1 mm per day.
2
Upon reaching the distal end, axons will penetrate the adjacent spinal cord if chondroitinase has been used to remove inhibitory proteoglycans from the surrounding scar tissue.
3
Functional connectivity will be determined by electrophysiological and immunocytochemical detection of a response by spinal cord neurons to stimulation of the axons within the graft.

Research Summary

One of the goals of our research is to promote axon regeneration to restore connectivity across the lesion site. Importantly, the peripheral nerve grafting approach is effective in promoting regeneration by acute and chronically injured neurons. With the peripheral nerve grafting approach described above we have demonstrated that adult motor and sensory neurons will regenerate their injured axonal process for long distances when provided with an appropriate substratum for growth.

Practical Implications

Treatment Strategy

The peripheral nerve grafting approach can be used as an acute or delayed treatment strategy for spinal cord injury.

Model Applicability

This approach can be applied successfully to small (mouse, rat) and large (cat) experimental animals.

Advantage over Other Methods

The peripheral nerve graft model provides relatively easy access to all of the axons bridging a spinal cord lesion, which is an advantage over other transplantation approaches.

Study Limitations

1
Reproducibility depends on consistent level of spinal cord injury.
2
Peripheral nerve must be pre-degenerated before transplantation.
3
Direct apposition of the peripheral nerve graft to the spinal cord and securing the graft with sutures is critical.

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