Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin/β1 integrin pathway

Journal of Neuroinflammation, 2021 · DOI: https://doi.org/10.1186/s12974-020-02059-x · Published: January 12, 2021

Simple Explanation

Spinal cord injury (SCI) often results in glial scar formation, which inhibits axon regeneration. This study investigates the effects of anti-β1 integrin antibody (β1Ab) treatment on microglia, a type of immune cell, within these glial scars. The research found that β1Ab treatment led to microglia scattering within the glial scar and a significant suppression of TNFα expression, a marker for inflammation, in both microglia and the scar tissue. Further investigation revealed that this effect is mediated by fibronectin, a protein that binds to β1 integrin receptors. Reactive astrocytes (RAs) secrete fibronectin, which then interacts with microglia to promote inflammation.

Study Duration

42 days

Participants

94 female C57BL/6N mice

Evidence Level

Not specified

Key Findings

1
β1Ab treatment altered microglial distribution within the glial scar after SCI, promoting a more even distribution instead of concentration in the lesion core.
2
TNFα expression was significantly downregulated in both the glial scar and microglia of β1Ab-treated mice, while Msr1 expression (an anti-inflammatory marker) was upregulated.
3
Fibronectin, secreted by reactive astrocytes, was identified as a key mediator in the interaction between astrocytes and microglia, promoting a pro-inflammatory microglial phenotype.

Research Summary

This study demonstrates that microglial inflammation after spinal cord injury is enhanced by reactive astrocytes through the fibronectin/β1 integrin pathway. Administration of β1Ab can ameliorate both glial scar formation and persistent neuroinflammation in the chronic phase after SCI. The findings suggest a therapeutic potential for β1Ab in modulating the glial scar pathology and improving the microenvironment after chronic SCI by blocking the intercellular interaction between reactive astrocytes and microglia.

Practical Implications

Therapeutic Target Identification

The fibronectin/β1 integrin pathway can be targeted to reduce neuroinflammation and glial scar formation after SCI.

Drug Development

β1Ab administration shows promise as a therapeutic strategy for ameliorating both glial scar formation and persistent neuroinflammation in chronic SCI.

Understanding Cell Interactions

The study highlights the importance of understanding the complex bidirectional interactions between microglia and astrocytes in the pathophysiology of chronic SCI.

Study Limitations

1
The study used a mouse model, and the results may not be directly applicable to humans.
2
Mass spectrometry was not performed to fully characterize the proteins in RACM that activate microglia.
3
P3 astrocytes used for cell culture are immature and may not have the same properties as adult mature astrocytes.

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