New insights into glial scar formation after spinal cord injury

Cell and Tissue Research, 2022 · DOI: https://doi.org/10.1007/s00441-021-03477-w · Published: June 2, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Severe spinal cord injury (SCI) leads to permanent loss of function and sensation due to the formation of a glial/fibrotic scar, which remodels the cellular architecture and extracellular matrix of the spinal cord. This scar, while initially beneficial for preserving function after injury, impedes axon regeneration and functional recovery over time. Innovative research using next-generation sequencing technologies is providing new insights into the molecular mechanisms governing the glial scar formation and its impact on regeneration, paving the way for potential therapeutic strategies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Single-cell RNA sequencing reveals that the glial scar penumbra is rich in proliferating oligodendrocyte progenitor cells, significantly contributing to CSPG deposition and lesion site remodeling.
2
Neonatal microglia promote scar-free wound healing and axonal growth, whereas adult microglia contribute to scar formation that inhibits regeneration.
3
Modulating the proteoglycan receptor PTPσ can rescue entrapped growth cones and enhance recovery after SCI.

Research Summary

This review summarizes the regeneration potential of the CNS across different species and ages, highlighting the role of scar-like structures in this process. It discusses how next-generation sequencing has revealed the complex molecular mechanisms governing astrocyte, microglial, and neuronal responses to injury, particularly in the glial component of the scar. The review concludes by exploring potential combinatorial therapeutic approaches centered on scar modulation to restore function after severe CNS injury.

Practical Implications

Therapeutic Targets

Identifying and targeting specific molecular components of the glial scar, such as CSPGs and their receptors, may promote axon regeneration and functional recovery.

Age-Specific Therapies

Developing therapies that mimic the regenerative environment of the neonatal spinal cord, by modulating microglial activity and promoting scar-free wound healing, could be more effective in adults.

Combinatorial Approaches

Combining strategies that enhance intrinsic neuronal growth capacity with those that modify the inhibitory environment of the glial scar may lead to synergistic improvements in functional outcomes.

Study Limitations

1
Single-cell RNA sequencing may miss rare cell types without specific enrichment methods.
2
Interpretation of genomic changes can be challenging in linking specific gene changes back to biological significance.
3
Lack of a common naming convention for newly identified subcellular populations makes collaboration difficult.

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