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  4. Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

Neural Regeneration Research, 2025 · DOI: https://doi.org/10.4103/NRR.NRR-D-23-01130 · Published: April 3, 2024

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Following a spinal cord injury, the body's natural response includes inflammation and scar tissue formation, which unfortunately can hinder nerve tissue repair. This study explores how two types of brain cells, microglia and astrocytes, interact in this process. The research found that a protein called Gas6, along with its receptor Axl, are reduced after a spinal cord injury. Introducing Gas6 appears to lessen the activation of both microglia and astrocytes, reducing inflammation and scar formation. By using Gas6 to modulate the activity of these cells, the study suggests a potential therapeutic strategy to improve spinal cord injury outcomes by fostering tissue repair and regaining motor function.

Study Duration
Specified time points: 1, 3, and 7 days post-injury and 8 weeks for behavioral and histological analyses
Participants
Adult female Sprague-Dawley rats (aged 3–5 weeks, 200–220 g)
Evidence Level
Not specified

Key Findings

  • 1
    After spinal cord injury, microglia polarize into pro-inflammatory phenotypes (MG1 and MG3), while astrocytes polarize into reactive and scar-forming phenotypes, with Gas6 and Axl expression significantly down-regulated in both cell types.
  • 2
    Gas6 inhibits the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway, which in turn inhibits the polarization of pro-inflammatory microglia by suppressing the activation of the NF-κB/p65 and JAK/STAT signaling pathways.
  • 3
    In vivo experiments demonstrated that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes, promoting tissue repair and motor function recovery in the injured spinal cord.

Research Summary

The study investigates the interaction between microglia and astrocytes after spinal cord injury (SCI) and the role of Growth arrest-specific 6 (Gas6) in this interaction. Results showed that Gas6 can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord. The findings suggest that Gas6 may be a potential therapeutic agent in SCI to prevent interaction between the pro-inflammatory microglial phenotype and cytotoxic astrocytic phenotype, which is a main cause of neural impairment.

Practical Implications

Therapeutic Target

Gas6/Axl signaling pathway can be targeted to modulate inflammatory responses in SCI.

Drug Development

Gas6 or Gas6 mimetics could be developed as potential therapeutics for SCI.

Cellular Interactions

Understanding the interactions between microglia and astrocytes is crucial for developing effective SCI treatments.

Study Limitations

  • 1
    Whether crosstalk occurs among these pro-inflammatory microglia phenotype and cytotoxic astrocyte phenotype-related signaling pathways needs further investigation.
  • 2
    The specific roles of these signaling pathways will aid the treatment of patients with SCI at an early stage requires more research.
  • 3
    Specific ablation and over-expression of Gas6 in microglia and astrocytes needs to be performed in SCI animal models to specifically verify the effects of Gas6 on the inflammatory micro-environment after SCI.

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