Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord

The Journal of Neuroscience, 2006 · DOI: 10.1523/JNEUROSCI.3900-05.2006 · Published: May 3, 2006

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

When the brain or spinal cord is injured, damaged axons fail to regrow and establish functional connections with their appropriate target cells. The principal environmental feature of the damaged CNS is the glial scar. This complex tissue acts as a physical and biochemical barrier to axon regeneration. Here, we used an antibody-mediated neutralization approach to analyze the functions of NG2 after SCI.

Study Duration

1 week and 4 weeks

Participants

Adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Treatment of acute spinal cord injuries with antibodies that neutralize NG2 function can promote the regeneration of ascending mechanosensory axons.
2
After treatment with neutralizing antibodies, labeled axons grew past the caudal penumbra and entered the lesion core.
3
After treatment with the neutralizing antibodies, although many axons still grow preferentially on the dorsal surface of the cord, a significant fraction of the axons enter and extend within the white matter

Research Summary

After treatment with antibodies that bind to and neutralize specifically the NG2 proteoglycan, medium- and large-diameter mechanosensory axons grow into the growth nonpermissive environment of the glial scar when combined with a previous peripheral nerve conditioning lesion, grow past the scar and into the degenerating white matter rostral to the lesion site. These findings show that the accumulations of NG2 at injury sites are a significant factor in the failure of axon regeneration and emphasize the utility of combinatorial treatments that target both the environment through which axons must regrow and the intrinsic growth state of the injured neuron.

Practical Implications

Therapeutic Target

NG2 proteoglycan is a potential therapeutic target for promoting axon regeneration after spinal cord injury.

Combinatorial Therapy

Combining anti-NG2 antibody treatment with peripheral nerve conditioning lesion enhances axon regeneration.

Anatomically Correct Regeneration

The approach used in this study promotes anatomically correct axon regeneration, which is essential for functional recovery.

Study Limitations

1
The study focuses on mechanosensory axons; the regeneration of other types of axons may be different.
2
The effectiveness of anti-NG2 antibodies may be context-dependent and influenced by other molecules in the environment.
3
The results may not be directly applicable to humans due to differences in the glial scar composition and regenerative capacity.

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