Role of myelin-associated inhibitors in axonal repair after spinal cord injury

Exp Neurol, 2012 · DOI: 10.1016/j.expneurol.2011.05.001 · Published: May 1, 2012

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

Spinal cord injuries lead to changes in the nervous system, but the central nervous system (CNS) axons do not regenerate. One reason might be the presence of molecules that inhibit axons from regenerating past the injury. Myelin-associated inhibitors like Nogo, MAG, and OMgp have been heavily researched, but there are conflicting results regarding their role in axon regeneration. These conflicting results could be due to different definitions of axon regeneration. To avoid confusion, regeneration is defined as the growth of injured axons, while sprouting is defined as the growth of uninjured axons. Both regeneration and sprouting are forms of injury-induced axonal growth that contribute to functional recovery.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Genetic analysis using Nogo knockout mice produced different outcomes ranging from robust, suggestive, to no regeneration, which have led to a major controversy regarding Nogo’s role in axon regeneration.
2
MAG mutants unexpectedly displayed less sprouting than wild-type controls, suggesting that MAG may be required for compensatory sprouting of corticospinal axons after pyramidotomy.
3
After a lateral hemisection, MAG and OMgp single knockouts displayed enhanced sprouting of serotonergic axons.

Research Summary

Myelin-associated inhibitors of axon growth, including Nogo, MAG and OMgp, have been the subject of intense research to promote axonal repair after spinal cord injury. Different definitions of axon sprouting vs. regeneration, the technical difficulty in distinguishing sprouting and regenerating axons and variable degrees of axon sparing in different studies are at least partly responsible for some of the discrepant findings. There seems to be a general consensus that myelin-associated inhibitors, namely Nogo, MAG and OMgp, do in fact inhibit axonal growth. The real division seems to occur when classifying the type of axonal growth that is affected by the experimental manipulations (i.e. axon regeneration vs. sprouting).

Practical Implications

Therapeutic Strategies

Understanding the mechanistic differences between sprouting and regeneration is crucial for developing effective therapeutic strategies for spinal cord injury.

Clinical Trials

Treating patients with complete spinal cord injury with treatments that primarily promote sprouting may lead to false negatives, delaying potential treatments for incomplete injuries.

Drug development

The complex roles of MAG cautions against a therapeutic strategy that indiscriminately targets all myelin-associated inhibitors and further underscore the importance of a thorough understanding of different myelin- associated inhibitors.

Study Limitations

1
Difficulty in distinguishing between regeneration and sprouting in experimental injury models.
2
Potential for axon sparing to complicate the analysis of axon regeneration.
3
Discrepancies in results from different laboratories attributed to variations in experimental manipulations and analyses.

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