Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

Mediators of Inﬂammation, 2017 · DOI: http://dx.doi.org/10.1155/2017/9478542 · Published: January 19, 2017

Regenerative Medicine Immunology Neurology

Simple Explanation

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Stimulation of inflammation has proven to be one of the pivotal factors to induce a regenerative response in mammalian axonal regeneration models.
2
After spinal cord injury, proinflammatory, M1-like macrophages are associated with secondary tissue damage, neuronal loss, axon retraction and demyelination, while anti-inflammatory, M2-like macrophages are assumed to be protective and promoting axon growth.
3
Unlike mammals, zebrafish possess a powerful regenerative capacity after CNS lesions, which leads to successful repair and seems to coincide with a favourable inflammatory state.

Research Summary

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. Unlike mammals, zebrafish possess a powerful regenerative capacity after CNS lesions, which leads to successful repair and seems to coincide with a favourable inflammatory state. Increasing evidence for a detrimental effect of inflammaging on the regenerative outcome is emerging, but further in-depth characterization in both mammals and zebrafish is highly warranted.

Practical Implications

Therapeutic Strategies

Modulation of the acute inflammatory response has been proposed as promising strategy to induce axonal regeneration.

Understanding Regeneration

Further uncovering of the mechanisms that control inflammatory and regenerative processes might provide fruitful insights that may lead to the identification of innovative therapeutic targets for human patients.

Aging Considerations

Aging processes affect the already limited regenerative potential in mammals. Since the innate immune system is subjected to aging as well, it is assumed to react differently to injuries in aged individuals.

Study Limitations

1
The regenerative potential is not equal for all axons in the spinal cord, as some axon types show only poor regrowth.
2
In-depth characterization of the role of acute inflammation in zebrafish spinal cord regeneration is lacking.
3
The impact of (inflamm)aging on the normally flawless regenerative process in the zebrafish CNS is scarcely studied and awaits further in-depth characterization.

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