Glucocorticoids Target Ependymal Glia and Inhibit Repair of the Injured Spinal Cord

Front. Cell Dev. Biol., 2019 · DOI: 10.3389/fcell.2019.00056 · Published: April 24, 2019

Simple Explanation

Following spinal cord injury, mammals form a glial scar and cannot regenerate, unlike fish. This study investigates why mammals cannot regenerate after such injuries, while fish can. The study found that glucocorticoids, often used in spinal cord injury management, hinder neural repair by affecting ependymal glia, a type of cell involved in regeneration. In zebrafish, the glucocorticoid receptor in ependymal glia becomes inactive after injury, whereas it becomes active in rats. This difference may explain why mammals don't regenerate spinal cords well.

Study Duration

Not specified

Participants

Zebrafish larvae and adult Fischer rats

Evidence Level

Not specified

Key Findings

1
Glucocorticoids inhibit functional recovery from spinal cord injury by impairing the ability of ependymal glia to support regeneration.
2
Glucocorticoids suppress the formation of glial bridges that are necessary for axon regrowth after spinal cord injury.
3
Glucocorticoids inhibit ependymal glial proliferation and neurogenesis following spinal cord injury, reducing the generation of new neural cells.

Research Summary

This study demonstrates that glucocorticoid receptor signaling in ependymal glia acts as a critical negative regulator of functional regeneration in the injured spinal cord. Glucocorticoids limit the formation of ependymal glial bridges, axon regeneration, ependymal glial proliferation, and neurogenesis, thus inhibiting the regenerative process. The differential regulation of ependymal glia by glucocorticoids in mammals and zebrafish may explain the limited regeneration observed in the mammalian spinal cord following injury.

Practical Implications

Therapeutic Implications

The findings suggest that conventional corticosteroid therapy may compound the failure of the injured spinal cord to regenerate. This highlights the need to re-evaluate the use of glucocorticoids in early management of spinal cord injury.

Targeted Anti-GC Therapy

The study supports the design of preclinical studies to test the efficacy of targeted anti-glucocorticoid therapy, potentially in combination with synergistic agents to stimulate ependymal glia and promote functional recovery.

Understanding Species-Specific Regeneration

The research elucidates critical differences in glucocorticoid receptor signaling between zebrafish and rats, offering insights into why regeneration is more successful in zebrafish and suggesting potential targets for enhancing regeneration in mammals.

Study Limitations

1
The study primarily uses zebrafish models, which may not fully represent the complexities of mammalian spinal cord injury.
2
Further research is needed to validate these findings in more complex mammalian models and clinical settings.
3
The specific mechanisms by which glucocorticoids regulate Sox2 expression in ependymal glia require further investigation.

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