A Novel Growth-Promoting Pathway Formed by GDNF-Overexpressing Schwann Cells Promotes Propriospinal Axonal Regeneration, Synapse Formation, and Partial Recovery of Function after Spinal Cord Injury

The Journal of Neuroscience, 2013 · DOI: 10.1523/JNEUROSCI.2973-12.2013 · Published: March 27, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study explores a new method to help nerves regenerate after spinal cord injury. The researchers created a 'growth-promoting pathway' using special cells that release a growth factor called GDNF. This pathway was designed to bridge the injury site and extend into the spinal cord, encouraging nerve cells to regrow and reconnect. The idea is to restore the communication between the brain and the spinal cord, which is disrupted by the injury. The experiments showed that this approach led to some nerve regeneration, new connections forming, and partial recovery of movement in rats with spinal cord injuries.

Study Duration

6 Weeks

Participants

51 adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Grafted Schwann cells overexpressing GDNF promoted regeneration of descending propriospinal (DPST) axons through and beyond the lesion gap of a spinal cord hemisection.
2
Regenerated DPSN axons formed synapses with host neurons within the distal host spinal cord, leading to restoration of action potentials.
3
The continuous growth-promoting pathway resulted in partial recovery of hindlimb locomotor function in rats with spinal cord injuries.

Research Summary

The study demonstrates that a continuous growth-promoting pathway, constructed by grafting Schwann cells overexpressing GDNF within and caudal to a spinal cord injury, leads to anatomical regeneration of damaged propriospinal axons. This regeneration results in the formation of new synapses and myelin, as well as partial electrophysiological and behavioral recovery. The findings suggest that the supraspinal motor system can utilize these regenerated propriospinal axons as a functional relay to transmit commands down to the spinal cord.

Practical Implications

Therapeutic Potential

This strategy could offer a novel treatment opportunity for patients with severe spinal cord injuries by promoting nerve regeneration and functional recovery.

Pathway Construction

Constructing a continuous growth-permissive pathway is essential for overcoming growth-inhibitory environments at the graft-host interface after SCI.

Combined Approach

Combining Schwann cells with GDNF provides multiple benefits, including modifying the graft-host interface, providing trophic factor gradients, and rescuing local spinal neurons.

Study Limitations

1
The hemisection model has a limitation in distinguishing between regeneration and sprouting of axons.
2
It remains unclear how efficient the newly formed connections are in transducing information.
3
The extent and thickness of myelin formed along the regenerated axons are not fully determined.

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