Extrinsic and intrinsic determinants of nerve regeneration

Journal of Tissue Engineering, 2011 · DOI: 10.1177/2041731411418392 · Published: January 1, 2011

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After an injury to the central nervous system (CNS), axons often fail to regenerate, leading to lasting neurological problems. However, when the peripheral nervous system (PNS) is injured, axons can regenerate well, which may lead to regaining function. Failures in CNS regeneration can be attributed to inhibitory molecules found in the injured CNS, and the intrinsic regenerative potential of some CNS neurons is reduced during CNS maturation and after injury. A better understanding of the factors that limit axon regeneration will help in developing better treatments for nervous system injuries.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5, Review

Key Findings

1
Injured axons must detect damage to initiate a regenerative response, triggering calcium-based and retrograde transport-based signals.
2
Cytokines, while potentially promoting regeneration, are limited by SOCS proteins, which can curtail regenerative growth in certain CNS neurons.
3
PTEN deletion dramatically increases postembryonic regeneration after injury in RGCs and corticospinal neurons in the CNS and axon outgrowth in the PNS.

Research Summary

The injured human CNS has only limited ability to recover after injury, with little recovery correlating to long-distance axonal regeneration. Removal of glial-inhibitory molecules has not dramatically affected functional recovery or long-distance axonal regeneration. Removal of growth suppressor molecules allows robust, long-distance axonal growth, activating a regenerative response not normally accessible to most injured CNS neurons.

Practical Implications

Combination Therapies

Given the complexity of the injured CNS, single treatment approaches are unlikely to fully repair the CNS after injury. Combination therapies are increasingly prominent and have shown experimental promise.

Targeting Intrinsic Growth Suppressors

Focusing on the removal of intrinsic growth suppressor molecules may unlock regenerative potential not normally accessible to injured CNS neurons.

Modulating Inflammatory Response

Careful modulation of the inflammatory response, considering the limiting effects of SOCS proteins, may enhance regeneration in specific CNS neurons.

Study Limitations

1
Limited understanding of the complex interplay between glial and neuronal components in the injured CNS.
2
Current treatments don't appear to cause dramatic effect on functional recovery or long distance axonal regeneration
3
Complexity of the injured CNS makes it unlikely that a single treatment approach will repair the CNS after injury.

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