Role of Chondroitin Sulfation Following Spinal Cord Injury

Frontiers in Cellular Neuroscience, 2020 · DOI: 10.3389/fncel.2020.00208 · Published: August 5, 2020

Simple Explanation

Traumatic spinal cord injury leads to long-term neurological damage, resulting in a glial scar composed of various cells and extracellular matrix molecules like CSPGs. These CSPGs, especially their sulfated glycosaminoglycan (GAG) chains, inhibit axonal regeneration and plasticity, hindering recovery after injury. Understanding how CSPGs and their sulfation patterns contribute to this inhibition is crucial for developing new therapies to promote spinal cord repair.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
The sulfation patterns of GAG chains on CSPGs influence their biological activity and interactions with potential receptors, impacting axonal regeneration.
2
4-sulfation on CS GalNAc appears to play a significant role in mediating the inhibitory actions of CS, correlating with decreased neural plasticity with aging.
3
CS-E and DS bind to NgR1 and NgR3, and mice lacking both NgR1 and 3 showed increased regeneration after injury.

Research Summary

This review discusses the role of chondroitin sulfate proteoglycans (CSPGs) in the injury response following spinal cord injury, focusing on how sulfated glycosaminoglycan (GAG) chains inhibit plasticity and regeneration. The sulfation of GAG chains influences their biological activity and interactions with receptors, and comprehending the role of CSPGs in the glial scar is critical for developing new therapies. Combination therapies that overcome the limited growth capacity of adult neurons and the inhibitory properties of the glial scar will be necessary for effective spinal cord injury treatment.

Practical Implications

Targeted Therapies

Selective targeting of 4-sulfation on GAG chains, potentially with enzymes like ARSB, may offer an alternative strategy to chondroitinase ABC for promoting axonal regeneration.

Receptor Modulation

Modulating the activity of receptors like RPTPσ and NgR1/3, which interact with CSPGs, could enhance axonal growth and plasticity after spinal cord injury.

Combination Approaches

Employing multiple strategies, including overcoming the inhibitory cues from CSPGs and stimulating neuronal growth, could maximize functional neuronal recovery after SCI.

Study Limitations

1
Inconsistent in vitro experimental results due to heterogeneous CSPG composition.
2
Limited ability to sequence CS GAG chains, hindering understanding of structure-function relationships.
3
Absence of reagents limits understanding of how GAG chains interact with receptors and downstream signaling pathways.

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