Hydrogen Sulfide Sustained Release Donor Alleviates Spinal Cord Ischemia–Reperfusion-Induced Neuron Death by Inhibiting Ferritinophagy-Mediated Ferroptosis

CNS Neuroscience & Therapeutics, 2025 · DOI: https://doi.org/10.1111/cns.70366 · Published: March 11, 2025

Simple Explanation

This study investigates spinal cord ischemia–reperfusion injury (SCIRI), a complication that can occur during thoracoabdominal aneurysm surgery. The researchers focus on a specific type of cell death called ferroptosis and how it's related to SCIRI. The study explores how hydrogen sulfide (H2S), a gasotransmitter, can protect nerve cells from dying after SCIRI. They found that H2S helps by controlling a process called ferritinophagy, which is linked to ferroptosis. The findings suggest that using H2S could be a new way to treat SCIRI, by preventing nerve cell death caused by problems with iron and cell waste disposal.

Study Duration

Not specified

Participants

Male Sprague–Dawley (SD) rats (188–200 g weight)

Evidence Level

Not specified

Key Findings

1
SCIRI induces autophagic ferritin degradation, leading to iron-dependent ferroptosis.
2
Hydrogen sulfide (H2S) attenuates neuron death by inhibiting ferritinophagy and ferroptosis in SCIRI.
3
Ferritinophagy-mediated ferroptosis contributes to the etiopathogenesis of SCIRI.

Research Summary

This study investigates the role of ferritinophagy-mediated ferroptosis in spinal cord ischemia-reperfusion injury (SCIRI) and the potential therapeutic effects of hydrogen sulfide (H2S). The results showed that SCIRI induces ferroptosis through autophagic degradation of ferritin, leading to iron accumulation and lipid peroxidation. H2S was found to alleviate neuronal death by inhibiting this process. The findings suggest that H2S could be a potential treatment for SCIRI by targeting ferritinophagy-mediated ferroptosis, offering a new strategy for reversing neuron damage and improving patient outcomes.

Practical Implications

Therapeutic Target Identification

Ferritinophagy-mediated ferroptosis is identified as a potential therapeutic target for SCIRI.

Drug Development

Sustained release H2S donors could be developed as a clinical treatment for reversing neuron damage in SCIRI.

Treatment Strategy

Modulating neuronal iron homeostasis and inhibiting lipid peroxidation via H2S could improve outcomes for patients with SCIRI.

Study Limitations

1
The study is limited to a rat model of SCIRI.
2
The specific mechanisms of H2S in regulating ferritinophagy and ferroptosis require further investigation.
3
The long-term effects of H2S treatment on SCIRI recovery were not assessed.

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