Know How to Regrow—Axon Regeneration in the Zebraﬁsh Spinal Cord

Cells, 2021 · DOI: 10.3390/cells10061404 · Published: June 6, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After spinal cord injury (SCI), humans often experience permanent functional deficits due to the inability of severed axonal fibers to regrow across the lesion site, preventing locomotor function recovery. There is currently no effective treatment to reverse this pathology. Unlike mammals, aquatic species like zebraﬁsh can regenerate their central nervous system (CNS) axons, including the brain and spinal cord, even into adulthood, allowing them to recover functionality after injury. Understanding how zebraﬁsh achieve this could lead to new treatments for humans. This review focuses on zebraﬁsh, which, due to their genetic amenability and excellent optical properties at larval stages, have provided a mechanistic insight on how the spinal cord can be successfully repaired after injury.

Study Duration

Not specified

Participants

Zebraﬁsh

Evidence Level

Review

Key Findings

1
Zebraﬁsh can recover swimming activity after spinal cord injury because of axonal projections regrowing across the injury site. Hindering axonal regrowth experimentally prevents functional recovery, and re-transecting regenerated spinal cords abolishes restored swimming activity.
2
After SCI in zebraﬁsh, an acute inflammatory response is necessary and sufficient for axonal regrowth. A timed response of consecutively appearing neutrophils and macrophage/microglia occurs.
3
In zebraﬁsh, pdgfrb+ fibroblasts are required for axon regeneration and functional recovery, secreting a regeneration-permissive ECM enriched in growth-promoting molecules and deprived of growth-limiting matrix molecules.

Research Summary

Mammals have poor long-distance axon regeneration and functional recovery after spinal cord injury, unlike zebraﬁsh. Understanding the cellular and molecular basis of this difference is a focus of research. Zebraﬁsh models are valuable for studying spinal cord regeneration due to their genetic amenability and optical properties. They offer mechanistic insights into how the spinal cord can be successfully repaired after injury. Zebraﬁsh SCI models are categorized by injury mechanism, site, and organism used. Mechanical lesions, cell ablation paradigms, and electroablation are among the techniques used to study axon regeneration.

Practical Implications

Therapeutic Targets for Humans

Insights from zebraﬁsh spinal cord regeneration, such as the role of TNF-α, may identify potential therapeutic targets for promoting functional recovery after SCI in humans.

Biomaterial Scaffold Strategies

Understanding the differences in mechanical properties of the lesion environment between regenerating and non-regenerating species can inform the development of biomaterial scaffolds to stimulate axon regeneration in mammals.

Drug Screening Platform

The zebraﬁsh SCI larval model can be used as a platform for small molecule in vivo screens. This combined with high-throughput, automated imaging and analysis platforms, can greatly accelerate the identification of potential targets to foster functional recovery after SCI in non-regenerating vertebrates.

Study Limitations

1
A systematic analysis on the regenerating axonal subtypes after SCI is currently missing as studies have mainly used pan-neuronal markers to label neurites.
2
Although a holistic understanding of the mechanisms underlying successful CNS regeneration in these species is still elusive, important cellular and molecular players have been identiﬁed.
3
Conditional, cell type-speciﬁc manipulations are imperative to dissect the contribution of the complex neural and non-neural cell responses to the lesion environment and axon regeneration.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury