Microglial activation in the motor cortex mediated NLRP3-related neuroinﬂammation and neuronal damage following spinal cord injury

Frontiers in Cellular Neuroscience, 2022 · DOI: 10.3389/fncel.2022.956079 · Published: October 20, 2022

Simple Explanation

Spinal cord injury can cause nerve damage that limits motor function recovery. This study found that after spinal cord injury, microglia in the motor cortex become activated. This activation triggers inflammation and damages neurons. Reducing microglial activation with a drug called minocycline can protect neurons and improve motor function recovery. Simulating inflammation in lab-grown neurons also caused damage, which could be reduced with minocycline, supporting the idea that microglial activation leads to neuronal damage after spinal cord injury.

Study Duration

28 days

Participants

Adult female Sprague–Dawley (SD) rats

Evidence Level

Not specified

Key Findings

1
Microglial activation in the motor cortex (M1) mediates NLRP3-related neuroinflammation following SCI.
2
NLRP3-related neuroinflammation in M1 induces neuronal damage.
3
Suppressing neuroinflammation in M1 improves the integrity of the motor conduction pathway and promotes locomotor function recovery after SCI.

Research Summary

This study found that microglial activation mediated NLRP3-related neuroinflammation in the motor cortex after SCI, which resulted in the injury to motor neurons, affected the integrity of motor pathways, and delayed motor function recovery. Treatment with minocycline attenuated the inflammatory environment, prevented neuronal damage, improved the integrity of motor pathways, and promoted motor function recovery. Preventing the neurotoxicity of NLRP3 inflammasome on cortical motor neurons may be a promising therapeutic strategy to promote motor function recovery after SCI.

Practical Implications

Therapeutic Target Identification

The study identifies the NLRP3 inflammasome pathway as a potential therapeutic target for promoting motor function recovery after SCI by preventing neurotoxicity in cortical motor neurons.

Clinical Translation of Minocycline

The findings suggest that minocycline, an inhibitor of microglial activation, could be a potential therapeutic agent to attenuate inflammation, prevent neuronal damage, and improve motor function recovery in SCI patients.

Comprehensive SCI Treatment

The research highlights the importance of addressing brain changes, specifically neuroinflammation in the motor cortex, in addition to local tissue damage in the spinal cord, for a comprehensive approach to SCI treatment and motor function recovery.

Study Limitations

1
The optimal treatment time with minocycline was missed.
2
Whether the improvement of MEPs and motor function is due to the eﬀect of minocycline on M1 inﬂammation needs to be clariﬁed
3
Local SCI is a traumatic event that often requires early treatment with large doses of drugs.

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