Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

Frontiers in Cellular Neuroscience, 2020 · DOI: 10.3389/fncel.2020.00078 · Published: April 3, 2020

Simple Explanation

The glial scar, a major component of the SCI lesion, is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. It is increasingly accepted that the glial scar plays a dual role in the pathological process of SCI, both protective and inhibitory. The glial scar and scar-forming astrocytes play key roles in the recovery of SCI. A thorough analysis of the roles of the glial scar in SCI may help provide new views of SCI and identify novel therapeutic strategies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
The glial scar restricts the spread of inflammation to protect spared neural tissues after SCI.
2
Reactive astrocytes may receive inflammatory factors from the lesion site to transform into a neurotoxic phenotype in the context of SCI, which is consistent with the findings of Liddelow et al. (2017).
3
Scar-forming astrocytes exhibit environment-dependent plasticity and could serve as bridges for axonal regrowth under certain conditions.

Research Summary

The glial scar is primarily composed of scar-forming astrocytes and plays a crucial role in spinal cord regeneration. The glial scar plays a dual role in SCI, both protective and inhibitory, and its effects change dynamically as SCI progresses. Novel therapeutic strategies should attenuate the inhibitory roles of the glial scar while maintaining or amplifying its beneficial roles.

Practical Implications

Environmental Regulation of Astrocytic Fate

Modulating the cellular environment, particularly ECM molecules, can influence scar-forming astrocytes and promote recovery.

Direct Cell Reprogramming Strategies

Reprogramming astrocytes into functional neurons may supply neurons for axonal relay and modestly attenuate glial scar density.

Astrocytic Phenotype Remodeling Strategies

Remodeling astrocytic phenotypes, such as A1 astrocytes, can reduce neuronal loss and improve regeneration.

Study Limitations

1
The exact roles of M1 and M2 macrophages require more investigation.
2
Whether scar-forming astrocytes are the primary producers of CSPGs remains controversial.
3
The existence, biomarkers, and behavior of A1 astrocytes remain controversial, and the direct relationship between their reduction and functional recovery needs more proof.

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