Operation spinal cord regeneration: Patterning information residing in extracellular matrix glycosaminoglycans

Brain and Behavior, 2020 · DOI: 10.1002/brb3.1531 · Published: January 1, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries (SCIs) are devastating, with many complications beyond paralysis and loss of sensory function. Although spinal cord regeneration can revolutionize treatment for spinal cord injuries, the goal has not yet been achieved. Research reveals that growth factors, along with spinal cord extracellular matrix, especially glycosaminoglycans, regulates axonal regrowth. Degrading chondroitin sulfate glycosaminoglycans improves axonal sprouting and functional recovery after spinal cord injury in both rodents and rhesus monkeys. Patterning information residing in glycosaminoglycans might be key elements in restricting spinal cord regeneration. A recommended solution is not to edit the human genome, but to take advantage of the regenerative mechanism of axolotls.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Narrative Review

Key Findings

1
Glycosaminoglycans interact with hundreds of extracellular growth factors, chemokine, cytokines, proteases, and protease inhibitors and are essential for animal development.
2
Degrading chondroitin sulfate glycosaminoglycans by injecting the bacterial enzyme chondroitinase improves axonal sprouting and functional recovery after spinal cord injury in both rodents and rhesus monkeys.
3
Heparan sulfate glycosaminoglycans are key molecules required for brain development.

Research Summary

Spinal cord injuries are devastating, and spinal cord regeneration has not yet been achieved. Research during the past 30 years reveals that growth factors, along with spinal cord extracellular matrix, especially glycosaminoglycans, regulates axonal regrowth. Patterning information residing in glycosaminoglycans might be key elements in restricting spinal cord regeneration. A recommended solution is to take advantages of the regenerative mechanism of axolotls and the current knowledge about the structures and functions of glycosaminoglycans. The key signaling networks and key molecules that control both development and regeneration are highly conserved. Among them, the indirect gene products, heparan sulfate and chondroitin sulfate glycosaminoglycans, are among the key players required for animal development and regeneration as patterning molecules.

Practical Implications

Therapeutic Strategies

Targeting glycosaminoglycans to promote axonal regrowth and functional recovery after spinal cord injury.

Axolotl Regeneration Mechanism

Leveraging the regenerative capabilities of axolotls to understand and replicate spinal cord regeneration in humans.

Drug Development

Engineering glycosaminoglycan-based matrices for effective regenerative therapies for spinal cord injuries.

Study Limitations

1
Current knowledge of SCIs is mainly derived from animal models.
2
Axolotls do not develop adaptive immunity.
3
The human immune system plays a major role in wound healing and therefore not translatable to axolotl physiology.

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