Moving beyond the glial scar for spinal cord repair

Nature Communications, 2019 · DOI: https://doi.org/10.1038/s41467-019-11707-7 · Published: September 6, 2019

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Following spinal cord injury, a scar forms, which contains damage and isolates it. This scar, however, also inhibits tissue repair and recovery. The spinal injury scar comprises multiple cellular and extracellular components. The scar is not simply 'good' or 'bad.' It protects tissue while also inhibiting repair. Understanding and targeting specific aspects of the scar is key to aiding recovery. Therapeutic strategies aim to reduce scar formation or block inhibitory molecules associated with the scar. These include surgical, pharmacological, and genetic approaches.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
The spinal injury scar comprises multiple cellular and extracellular components beyond just glial cells, including fibroblasts, immune cells, and extracellular matrix.
2
Astrocytes play a dual role in spinal cord injury: they help to spatially isolate damage and fibrosis from spared tissue, but they also contribute to the chronic maintenance of the scar structure.
3
Chondroitin sulfate proteoglycans (CSPGs) are upregulated by reactive glia and are associated with decreased plasticity and abortive regeneration, representing therapeutic targets.

Research Summary

The spinal injury scar is a complex entity comprising various cell types and extracellular components that interplay to modulate tissue repair and regeneration after spinal cord injury. Reactive astrocytes have both beneficial (preventing the spread of cellular damage) and detrimental (limiting new growth and tissue repair) properties, influencing the overall outcome after SCI. Therapeutic strategies aimed at manipulating the scar should focus on targeting detrimental aspects, such as CSPGs, while preserving the beneficial properties, like the glia limitans formation.

Practical Implications

Targeted Therapies

Develop therapies that specifically target the detrimental aspects of the scar, such as CSPGs, while preserving the beneficial properties like spatial isolation of damage.

Combination Therapies

Combine therapies that modulate the scar environment with those that promote neuronal regeneration and plasticity.

Temporal Considerations

Consider the timing of therapeutic interventions, as the molecular profile of the scar changes over time.

Study Limitations

1
The exact mechanisms underlying the opposing roles of astrocytes in spinal cord injury are not fully understood.
2
The complexity of the scar microenvironment makes it challenging to selectively target specific components without affecting others.
3
Translation of preclinical findings to human clinical trials remains a significant hurdle.

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