Remote ischemic preconditioning protects against spinal cord ischemia–reperfusion injury in mice by activating NMDAR/AMPK/PGC‑1α/SIRT3 signaling

Cell & Bioscience, 2023 · DOI: https://doi.org/10.1186/s13578-023-00999-4 · Published: March 27, 2023

Spinal Cord Injury Cardiovascular Science Neurology

Simple Explanation

This study explores how a technique called remote ischemic preconditioning (RIPC) can protect the spinal cord from damage after a period of reduced blood flow, followed by the restoration of blood flow, known as ischemia-reperfusion injury (SCIRI). The researchers found that RIPC, which involves short cycles of reduced blood flow in a distant part of the body, helps to improve motor function recovery and reduce nerve cell loss in mice with SCIRI. They discovered that a protein called SIRT3 plays a crucial role in this protective effect, and that RIPC increases SIRT3 levels through a specific signaling pathway (NMDAR-AMPK-PGC-1α).

Study Duration

3 days

Participants

Adult male C57BL/6 J mice (20–25 g)

Evidence Level

Not specified

Key Findings

1
RIPC improves motor function and reduces neuronal loss after SCIRI in mice.
2
SIRT3 is essential for RIPC-mediated neuroprotection; without SIRT3, RIPC does not provide a protective effect.
3
RIPC upregulates SIRT3 levels via the NMDAR-AMPK-PGC-1α signaling pathway.

Research Summary

This study investigates the protective effects of remote ischemic preconditioning (RIPC) against spinal cord ischemia-reperfusion injury (SCIRI) in mice. The study identifies SIRT3 as a key protein mediating the neuroprotective effect of RIPC, with its levels being upregulated through the NMDAR-AMPK-PGC-1α signaling pathway. The findings suggest that combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Practical Implications

Therapeutic Target

SIRT3 can be a potential therapeutic target for SCIRI.

Combined Therapy

RIPC combined with SIRT3 agonists could be a more effective treatment for SCIRI.

Clinical Translation

RIPC before surgery and SIRT3 agonists after surgery may improve outcomes in patients at risk of SCIRI.

Study Limitations

1
The study is limited to mice models, and the results may not directly translate to humans.
2
The study focuses on SIRT3 and the NMDAR-AMPK-PGC-1α pathway, but other factors may also be involved in RIPC-mediated neuroprotection.
3
Further research is needed to optimize the timing and dosage of RIPC and SIRT3-targeting therapies.

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