The age factor in axonal repair after spinal cord injury: a focus on neuron-intrinsic mechanisms

Neurosci Lett, 2017 · DOI: 10.1016/j.neulet.2016.11.003 · Published: June 23, 2017

Spinal Cord Injury Aging Regenerative Medicine & Stem Cells

Simple Explanation

Age is a significant factor in spinal cord injury (SCI) and its repair, with an increasing number of middle-aged and older individuals affected by SCI. While progress has been made in promoting axon regeneration, understanding how age affects this repair remains limited, especially considering the limited regenerative ability of CNS axons in adult mammals. This review focuses on neuron-intrinsic mechanisms contributing to the age-dependent decline in axonal growth after central nervous system (CNS) injury, setting the stage for further discussion on this topic.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Axon regeneration declines with age in various systems, including zebrafish and C. elegans, suggesting the involvement of neuron-intrinsic mechanisms.
2
In the mammalian PNS, an age-dependent decline in regeneration is observed, possibly mediated by neuron-extrinsic mechanisms, such as reduced clearance of axon and myelin debris by Schwann cells.
3
PTEN deletion can unmask an age-dependent decline in axon regeneration in the adult mammalian CNS, suggesting that neuron-extrinsic mechanisms may underlie this decline.

Research Summary

Age is an important consideration for recovery and repair after spinal cord injury, with SCI increasingly affecting older populations. Despite progress in promoting axonal regeneration and repair, understanding how age modulates this repair is limited. The review focuses on neuron-intrinsic mechanisms for the age-dependent decline in axonal growth after CNS injury, while acknowledging the involvement of both intrinsic and extrinsic factors.

Practical Implications

Targeted Therapies

Development of therapies addressing neuron-intrinsic factors to counteract age-related decline in axon regeneration.

Model Refinement

Refinement of animal models to better reflect the age of human SCI patients, improving translational research.

Combination Strategies

Exploration of combined strategies targeting both neuron-intrinsic and -extrinsic mechanisms to enhance axon regeneration in aging individuals.

Study Limitations

1
The review primarily focuses on neuron-intrinsic mechanisms, potentially overlooking the significant contribution of neuron-extrinsic factors.
2
Limited studies have directly examined the effect of age on axon growth after injury in mammalian spinal cord injury models.
3
The complexity of chronic injury in axonal repair, particularly distinguishing between the effects of chronic injury versus age, poses a challenge for future studies.

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