Sialidase enhances spinal axon outgrowth in vivo

PNAS, 2006 · DOI: 10.1073/pnas.0604613103 · Published: July 18, 2006

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The adult central nervous system (CNS) inhibits axon growth, limiting recovery from injuries. This is partly due to axon regeneration inhibitors (ARIs) at injury sites. Sialidase, an enzyme, can cleave certain axonal receptors that bind to myelin-associated glycoprotein. This treatment enhances spinal axon growth in a rat model of brachial plexus avulsion. Peripheral nerve grafts are used to repair nerve damage, but improvement is limited. Using sialidase with these grafts could improve outcomes after injuries like brachial plexus avulsion.

Study Duration

4 weeks

Participants

Male Sprague–Dawley rats weighing 200–250 g

Evidence Level

Not specified

Key Findings

1
Infusion of Clostridium perfringens sialidase to the injury site markedly increased the number of spinal axons that grew into the graft.
2
Chondroitinase ABC, an enzyme that cleaves a different ARI (CSPGs), also enhanced axon outgrowth in this model.
3
Phosphatidylinositol-specific phospholipase C, which cleaves oligodendrocyte-myelin glycoprotein and Nogo receptors, did not show any benefit in enhancing axon outgrowth.

Research Summary

The injured CNS limits functional recovery due to axon regeneration inhibitors (ARIs). Reversing ARI action may enhance axon outgrowth and recovery after CNS injury. Sialidase or chondroitinase ABC enhanced innervation of peripheral nerve grafts. Data demonstrate a potential therapeutic benefit of sialidase in CNS injury. Sialidase enhances axon outgrowth by destroying axonal receptors for MAG, such as gangliosides GD1a and GT1b.

Practical Implications

Therapeutic Potential

Molecular therapies targeting sialoglycoconjugates and CSPGs may aid functional recovery after brachial plexus avulsion or other nervous system injuries and diseases.

Combination Therapy

Further experiments will be needed to test whether combining sialidase and chondroitinase ABC will result in yet greater enhancement of axon outgrowth.

Surgical Improvement

Sialidase and chondroitinase ABC each enhance axon regeneration into peripheral nerve grafts implanted into the spinal cord, providing two potential therapeutic targets to improve regeneration.

Study Limitations

1
The mechanism by which sialidase enhances axon outgrowth in vivo has yet to be established.
2
Quantitative removal of NgR and OMgp by PI-PLC was not established, leaving the possibility that residual NgR or OMgp were inhibitory.
3
Whether sialidase, alone or in combination with other ARI blockers, will enhance axon outgrowth in other nerve injury models has yet to be determined.

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