Melatonin Attenuates Spinal Cord Injury in Mice by Activating the Nrf2/ARE Signaling Pathway to Inhibit the NLRP3 Inflammasome

Cells, 2022 · DOI: 10.3390/cells11182809 · Published: September 8, 2022

Simple Explanation

Spinal cord injury (SCI) is a trauma to the central nervous system involving inflammation and oxidative stress, which contribute to the disease's development. Controlling inflammation is therefore a good SCI treatment strategy. Melatonin, a hormone, has antioxidant and anti-inflammatory effects. It also protects nerves in various neurological diseases. Melatonin can positively regulate the Nrf2/ARE/NLRP3 pathway, which is important for reducing inflammation and oxidation. This study investigated whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model, as the mechanism of melatonin's regulation of inflammation during SCI is not well understood.

Study Duration

28 days

Participants

100 C57BL/6 mice

Evidence Level

Level 1: In vivo and in vitro study

Key Findings

1
Melatonin promotes the recovery of neuromotor function by inhibiting neuroinflammation and reducing neuronal death.
2
Melatonin reduces neuronal mitochondrial dysfunction, reduces reactive oxygen species (ROS) and malondialdehyde levels, and enhances superoxide dismutase activity and glutathione peroxidase production.
3
Melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling pathway.

Research Summary

This study investigates the neuroprotective effects of melatonin on spinal cord injury (SCI) in mice, focusing on the Nrf2/ARE/NLRP3 pathway. The results demonstrate that melatonin promotes neuromotor recovery by reducing neuroinflammation, neuronal death, and mitochondrial dysfunction. The study concludes that melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, improving nerve function recovery after SCI and suggesting a new therapeutic option.

Practical Implications

Therapeutic Potential

Melatonin shows promise as a therapeutic agent for spinal cord injury by mitigating oxidative stress and inflammation.

Pathway Target

The Nrf2/ARE pathway is identified as a key target for melatonin's neuroprotective effects in SCI.

Clinical Relevance

The findings provide a basis for future clinical trials to evaluate melatonin's efficacy in SCI patients, given its limited side effects.

Study Limitations

1
The study did not use Nrf2-knockout mice for in-depth research.
2
The study needs different doses of melatonin in different periods of SCI to test how melatonin affects SCI more systematically and comprehensively.
3
Restricted conditions limited further research.

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