Axonal regeneration after spinal cord injury in zebrafish and mammals: differences, similarities, translation

Neurosci Bull, 2013 · DOI: 10.1007/s12264-013-1361-8 · Published: August 1, 2013

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury in mammals often leads to permanent deficits because damaged nerve fibers (axons) can't regrow. This review explores why this regeneration fails in mammals compared to zebrafish, which have a better capacity for axonal regeneration after spinal cord injury. The review compares factors inside the nerve cells (intrinsic) and outside (extrinsic) that affect axon regrowth in both mammals and zebrafish. Understanding these differences could help develop new treatments for spinal cord injuries. Zebrafish offer a unique opportunity to study successful and failed axon regeneration because some of their nerve fibers regenerate well while others don't, even within the same environment. Identifying the key molecules involved could lead to therapies that promote regeneration in mammals.

Study Duration

Not specified

Participants

Zebrafish and mammals

Evidence Level

Review

Key Findings

1
Mammalian CNS axons do not spontaneously regenerate after a lesion due to extrinsic (lack of growth-promoting molecules and surplus of growth-inhibitory molecules) and intrinsic mechanisms.
2
In zebrafish, some brainstem neurons can regenerate axons across a spinal cord injury, leading to functional recovery; however, not all axons regenerate, suggesting intrinsic differences.
3
Key molecules like GAP-43, L1CAM, CRP1, contactin-2, MVP, and miR-133b are associated with successful axonal regeneration in zebrafish, offering potential targets for mammalian SCI therapies.

Research Summary

This review compares axonal regeneration after spinal cord injury (SCI) in mammals and zebrafish, highlighting the differences in intrinsic and extrinsic factors that contribute to regeneration failure or success. Mammalian SCI results in permanent deficits due to growth-inhibitory molecules and limited intrinsic regenerative capacity, while zebrafish exhibit successful regeneration in some axons. Identifying key molecules and pathways in zebrafish that promote axonal regeneration, such as GAP-43, L1CAM, CRP1, contactin-2, MVP and miR-133b, may provide therapeutic targets for promoting regeneration in mammalian SCI.

Practical Implications

Therapeutic Targets

Identifying specific molecules, like CRP1, contactin-2, MVP, and miR-133b, involved in successful zebrafish axonal regeneration could lead to new therapeutic targets for mammalian SCI.

Combination Therapies

A better understanding of the individual characteristics of neurons with regard to their regenerative propensity may point at the necessity for interventions in more common mechanisms or multiple interventions in separate mechanisms to achieve significant axonal regeneration.

Personalized Medicine

Understanding the intrinsic properties of different neuron types could allow for personalized therapies that enhance the regenerative capacity of specific neuronal populations after SCI.

Study Limitations

1
The review focuses primarily on zebrafish and mammals, potentially overlooking regenerative mechanisms in other species.
2
The exact mechanisms by which certain molecules (e.g., MVP) influence axonal regeneration in zebrafish are not fully understood.
3
Translating findings from zebrafish to mammals may be challenging due to differences in physiology and genetics.

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