SIRT1 attenuates blood-spinal cord barrier disruption after spinal cord injury by deacetylating p66Shc

Redox Biology, 2023 · DOI: https://doi.org/10.1016/j.redox.2023.102615 · Published: January 24, 2023

Simple Explanation

This study investigates the role of SIRT1, a protein involved in cell health, in protecting the blood-spinal cord barrier (BSCB) after a spinal cord injury (SCI). The BSCB is crucial for maintaining a stable environment in the spinal cord. The researchers found that SIRT1 expression decreases after SCI, and that increasing SIRT1 activity can help to preserve the BSCB, reduce inflammation, and improve recovery after SCI. The study identifies p66Shc, a protein involved in oxidative stress, as a target of SIRT1. SIRT1 appears to protect the BSCB by modifying p66Shc, reducing oxidative stress, and promoting a healthier environment in the spinal cord.

Study Duration

Not specified

Participants

Mice (SIRT1flox/flox, Tie2-Cre, C57BL/6J)

Evidence Level

Not specified

Key Findings

1
SIRT1 expression decreases in spinal cord endothelial cells after SCI, suggesting a potential role in BSCB disruption.
2
Knockout of endothelial SIRT1 exacerbates disruption of the BSCB, impairs functional recovery, and increases inflammation and neural cell death after SCI.
3
Activation of SIRT1 protects the BSCB and promotes functional recovery after SCI, confirming a critical role in protecting the BSCB function.

Research Summary

This study demonstrates that SIRT1 is highly expressed in endothelial cells of the spinal cord and that its expression decreases after SCI. Endothelial cell-specific knockout of SIRT1 exacerbates BSCB disruption, leading to increased inflammation and poor functional recovery. Conversely, activation of SIRT1 protects the BSCB and promotes functional recovery. SIRT1 interacts with and deacetylates p66Shc, a redox protein, thereby attenuating oxidative stress and protecting endothelial barrier function. The findings suggest that SIRT1 activation has potential as a therapeutic approach to promote functional recovery against BSCB disruption following SCI.

Practical Implications

Therapeutic Target for SCI

SIRT1 activation could be a promising therapeutic approach to promote functional recovery against BSCB disruption following SCI.

Oxidative Stress Reduction

Targeting SIRT1 may help reduce oxidative stress in endothelial cells after SCI, promoting BSCB integrity.

P66Shc Modulation

Modulating p66Shc activity through SIRT1 could offer a novel strategy to protect the BSCB and improve outcomes after SCI.

Study Limitations

1
The study focuses primarily on mice, and results may not directly translate to humans.
2
The precise mechanisms of SIRT1 regulation in different cell types of the spinal cord require further investigation.
3
The role of endothelial transporters or adherens junctions, contributing to BSCB dysfunction, were not further investigated.

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