Determinants of Axon Growth, Plasticity, and Regeneration in the Context of Spinal Cord Injury

American Journal of Pathology, 2018 · DOI: https://doi.org/10.1016/j.ajpath.2017.09.005 · Published: January 1, 2018

Spinal Cord Injury Regenerative Medicine Neuroplasticity

Simple Explanation

After a spinal cord injury, the central nervous system's ability to repair itself is limited. A major goal is to encourage axons, the long fibers that transmit nerve signals, to regrow. This regrowth is necessary for the nervous system to adapt, form new connections, and potentially restore function. However, even if axons regrow, it doesn't automatically mean that function is restored. The new connections need to be properly formed and integrated into existing neural circuits. Sometimes, axons can even create incorrect or harmful connections. This review examines the factors that affect axon regrowth after spinal cord injury, including both internal mechanisms within the nerve cells and external factors in the surrounding environment. Understanding these factors is crucial for developing effective treatments to promote meaningful recovery.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Injured axons in the CNS often fail to regenerate and form dystrophic end bulbs, which persist at the lesion border.
2
Axonal dieback occurs in two phases: an initial intrinsic retraction and a secondary phase mediated by infiltrating macrophages.
3
The glial scar, particularly chondroitin sulfate proteoglycans (CSPGs), inhibits axon regeneration.

Research Summary

This review surveys the mechanisms leading to the formation of dystrophic growth cone at the injured axonal tip, the subsequent axonal dieback, and the molecular determinants of axon growth, plasticity, and regeneration in the context of spinal cord injury. The review discusses intracellular mechanisms of regeneration impairment, including acute axonal degeneration, axonal retraction, and the dystrophic growth state. Extracellular mechanisms of regeneration failure are also explored, focusing on the formation of the glial scar, the role of CSPGs and their receptors, the phenomenon of entrapment, myelin components, and other inhibitors of axonal regeneration.

Practical Implications

Therapeutic Targeting of CSPGs

Modulating CSPG expression or blocking their receptors may promote axon regeneration and functional recovery after SCI.

Controlling Macrophage Activity

Inhibiting macrophage-mediated axonal dieback could enhance axon survival and regeneration.

Enhancing Intrinsic Growth Capacity

Strategies to increase the intrinsic growth capacity of CNS neurons, such as PTEN deletion or conditioning lesions, show promise for promoting regeneration.

Study Limitations

1
The review focuses primarily on rodent models of SCI.
2
The complexity of SCI pathology makes it difficult to translate findings directly to human patients.
3
The functional significance of axonal regrowth remains a challenge to determine, as anatomical regeneration does not always correlate with functional recovery.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury