Sodium butyrate alleviates spinal cord injury via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis

Metabolic Brain Disease, 2025 · DOI: https://doi.org/10.1007/s11011-025-01589-8 · Published: March 18, 2025

Spinal Cord Injury Neurology Gastroenterology

Simple Explanation

Spinal cord injury (SCI) can lead to motor dysfunction, and new treatments are needed. Pyroptosis, a form of inflammatory cell death, is linked to SCI's pathological mechanisms. The study investigates if sodium butyrate (NaB) can help with SCI recovery by affecting pyroptosis. The levels of short-chain fatty acids (SCFAs) like butyric acid are altered after SCI. Sodium butyrate (NaB), known for its anti-inflammatory properties, is studied for its potential effect on pyroptosis in a rat SCI model. The study found that NaB treatment promoted motor function recovery and reduced inflammation in rats with SCI. NaB inhibited pyroptosis by downregulating key proteins involved in the NLRP3/Caspase-1/GSDMD pathway, suggesting it could be an effective treatment for SCI.

Study Duration

28 days

Participants

84 male Sprague–Dawley (SD) rats

Evidence Level

Not specified

Key Findings

1
SCFAs levels, especially butyric acid, significantly decreased after SCI, indicating changes in gut flora metabolites.
2
NaB treatment promoted forelimb motor function recovery and attenuated pathological SCI, as evidenced by improved scores in cylinder rearing and grooming tests, and reduced spinal cord tissue damage.
3
NaB inhibited NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis and inflammation, exerting protective and therapeutic effects in SCI.

Research Summary

This study investigates the potential of sodium butyrate (NaB) to alleviate spinal cord injury (SCI) by inhibiting pyroptosis. It establishes that SCFAs levels, particularly butyric acid, are significantly reduced after SCI, and that NaB treatment can promote motor function recovery. The research demonstrates that NaB attenuates pathological spinal cord damage, reduces inflammation, and inhibits NLRP3/Caspase-1/GSDMD-mediated neuronal pyroptosis in SCI rats. These effects suggest that NaB has neuroprotective qualities that promote SCI recovery. The findings indicate that butyric acid from the microbiota may effectively promote SCI recovery, supporting NaB as a potential therapeutic intervention for SCI.

Practical Implications

Therapeutic Potential

Sodium butyrate could be explored as a therapeutic agent for spinal cord injury, given its ability to reduce inflammation and promote motor function recovery in rats.

Microbiota-Gut-Brain Axis

The study highlights the importance of the microbiota-gut-brain axis in SCI, suggesting that interventions targeting gut health could improve neurological outcomes.

Pyroptosis Inhibition

The research suggests that inhibiting pyroptosis, specifically via the NLRP3/Caspase-1/GSDMD pathway, is a viable therapeutic strategy for SCI.

Study Limitations

1
Limited to animal experiments without cellular validation.
2
Preliminary exploration of NaB's effect on the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway only.
3
Limited clinical evidence supporting neurological benefits in humans.

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