M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

Neural Regen Res, 2022 · DOI: 10.4103/1673-5374.324858 · Published: May 1, 2022

Simple Explanation

After spinal cord injury (SCI), astrocytes migrate to the lesion and deposit chondroitin sulfate proteoglycan, forming a scar that limits inflammation but hinders axon regeneration. Microglia accumulate at the lesion border, polarizing into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. This study investigates how microglia polarization affects astrocytes after SCI. Researchers found that M1-type microglia were primarily observed early after injury (3-7 days), while M2-type microglia appeared later (7-14 days). In vitro experiments revealed that M1 microglia highly expressed transforming growth factor-β1 (TGFβ1) and induced astrocytes to secrete chondroitin sulfate proteoglycan (CSPG). The study suggests that M1-type microglia induce astrocytes to deposit CSPG via the TGFβ1/SOX9 pathway. These findings contribute to understanding glial scar formation after SCI and may aid in developing therapeutic strategies to reduce CSPG deposition and promote axon regeneration.

Study Duration

Not specified

Participants

50 female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Microglia and astrocytes gather at the lesion border after spinal cord injury, with microglia closely adjacent to astrocytes.
2
M1-type microglia are predominant at 3 and 7 days post-injury, while M2-type microglia increase at 7 and 14 days post-injury.
3
M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.

Research Summary

This study investigates the effect of microglia polarization on astrocytes after spinal cord injury (SCI). It was found that microglia and astrocytes gather at the lesion border, with microglia closely interacting with astrocytes. M1-type microglia were predominant early after SCI, expressing high levels of TGFβ1. Conditioned media from M1-type microglia induced astrocytes to secrete CSPG in vitro, an effect that was eliminated by knocking down SOX9 in astrocytes. The findings suggest that M1-type microglia induce astrocytes to deposit CSPG via the TGFβ1/SOX9 pathway, potentially contributing to glial scar formation after SCI.

Practical Implications

Therapeutic Strategies

The findings may help develop new therapeutic strategies for reducing CSPG deposition, promoting axonal growth, and accelerating functional repair after SCI.

Targeting M1 Microglia

Targeting M1 microglia polarization or the TGFβ1/SOX9 pathway could be a potential approach to modulate astrocyte activity and promote axonal regeneration.

Understanding Glial Scar Formation

The study provides insights into the complex interactions between microglia and astrocytes during glial scar formation after SCI.

Study Limitations

1
Only a single antibody was used to detect M1/M2 polarization.
2
The study only investigated the TGFβ1/SOX9 pathway, but membrane receptors may also play an important role in the process.
3
Further in vivo experiments are needed to verify the conclusions.

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