Combining Schwann Cell Bridges and Olfactory-Ensheathing Glia Grafts with Chondroitinase Promotes Locomotor Recovery after Complete Transection of the Spinal Cord

The Journal of Neuroscience, 2005 · DOI: 10.1523/JNEUROSCI.3562-04.2005 · Published: February 2, 2005

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This study explores a combination therapy for spinal cord injury in rats, aiming to overcome obstacles to axon regeneration. The approach involves reducing inhibitory cues in the glial scar, providing a supportive substrate for axonal regeneration, and enabling axons to re-enter the spinal cord. The combination of Schwann cells, olfactory ensheathing glia, and chondroitinase ABC showed significant improvements compared to grafts alone or no treatment.

Study Duration

10 weeks

Participants

Adult female Fischer rats (165–180 g)

Evidence Level

Not specified

Key Findings

1
The combination of SC bridge, olfactory ensheathing glia, and chondroitinase ABC provided significant benefit compared with grafts only or the untreated group.
2
Significant improvements were observed in the Basso, Beattie, and Bresnahans score and in forelimb/hindlimb coupling.
3
This recovery was accompanied by increased numbers of both myelinated axons in the SC bridge and serotonergic fibers that grew through the bridge and into the caudal spinal cord.

Research Summary

The study investigates a combinatory strategy to promote axonal regeneration and functional recovery after complete spinal cord transection in adult rats. The treatment involved reducing inhibitory cues (chondroitinase ABC), providing a growth-supportive substrate (Schwann cells), and enabling axonal exit from the bridge (olfactory ensheathing glia). The combination of these treatments resulted in significant improvements in locomotor function and increased numbers of myelinated axons and serotonergic fibers.

Practical Implications

Future Treatment Development

The study provides needed direction for the development of future combinatory treatment regimens for spinal cord injury.

Additive Treatment Effects

The results demonstrate that the grafts consisting of SCs and OEG and the application of cABC have additive effects.

Importance of cABC

The application of cABC appears especially suited when applied in conjunction with grafted tissue, because scar tissue at the graft-host interface represents a barrier for axons to grow into and through the graft.

Study Limitations

1
The time course illustrates that recovery did not plateau at the end of the allotted testing period.
2
The laminectomy of three vertebral segments without artificial stabilization resulted in strong lordosis, further hampering locomotor recovery.
3
The lack of tracing of propriospinal interneurons limits the understanding of their role in the observed recovery.

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