Barriers to axonal regeneration after spinal cord injury: a current perspective

Neural Regeneration Research, 2022 · DOI: 10.4103/1673-5374.314299 · Published: January 1, 2022

Spinal Cord Injury Regenerative Medicine Immunology

Simple Explanation

Spinal cord injury (SCI) causes damage to white matter pathways, leading to neurologic deficits. This paper discusses pathological mechanisms that inhibit axonal regeneration after SCI and suggests therapeutic interventions to promote regeneration in animal models. After SCI, inflammation further damages axonal pathways. The type of inflammatory response depends on the injury location. Deep injuries result in a cavity of injury (COI) filled with necrotic debris and inflammatory cells, while surface injuries cause arachnoiditis, leading to scar formation. Barriers to axonal regrowth include the severity and duration of inflammation, the presence of the COI and syrinx, and the formation of scar tissue from arachnoiditis. Therapeutic strategies aim to inhibit inflammation, bridge the COI, and address myelin's inhibitory effects.

Study Duration

Not specified

Participants

Rat model

Evidence Level

Not specified

Key Findings

1
Severe inflammation following SCI, lasting over 16 weeks, is destructive to adjacent white matter.
2
The cavity of injury (COI) and resulting syrinx are not crossed by axons unless supported by an implanted bridge.
3
Arachnoiditis and the resulting scar cease to be part of the spinal cord, preventing CNS axons from entering.

Research Summary

Axonal regeneration after spinal cord injury is hindered by severe inflammation, the formation of a cavity of injury (COI) or arachnoiditis, and the presence of myelin. Inhibition of inflammation is a necessary first step, potentially achieved through sustained release of anti-inflammatory agents via hydrogels. Overcoming myelin's inhibitory effects on axonal regeneration can be accomplished by subdural infusion of kynurenic acid to remove myelin sheaths.

Practical Implications

Targeting Inflammation

Sustained anti-inflammatory therapies are crucial for neuroprotection and enabling the implantation of supportive materials.

Bridging the COI

Hydrogels or other materials can serve as a bridge for axonal regeneration across the COI, especially when combined with anti-inflammatory agents.

Myelin Removal

Controlled removal of myelin through agents like kynurenic acid can create areas conducive to axonal regrowth.

Study Limitations

1
Toxicity associated with long-term dexamethasone administration
2
Invasive nature of subdural infusion
3
Challenges in translating findings from animal models to human clinical trials

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