A slow‑releasing donor of hydrogen sulfide inhibits neuronal cell death via anti‑PANoptosis in rats with spinal cord ischemia‒reperfusion injury

Cell Communication and Signaling, 2024 · DOI: https://doi.org/10.1186/s12964-023-01457-x · Published: January 1, 2024

Simple Explanation

Spinal cord ischemia‒reperfusion injury (SCIRI) can lead to paraplegia, which leads to permanent motor function loss. It is a disastrous complication of surgery and causes tremendous socioeconomic burden. However, effective treatments for SCIRI are still lacking. PANoptosis consists of three kinds of programmed cell death, pyroptosis, apoptosis, and necroptosis, and may contribute to ischemia‒reperfusion-induced neuron death. This study explores whether H2S ameliorates SCIRI and was associated with anti-PANoptosis. The results reveal the protective properties of H2S at a proper dosage in the SCIRI rat model. The results of our studies not only reveal the protective properties of H2S at a proper dosage in the SCIRI rat model, but also demonstrate that H2S may ameliorate the consequences of SCIRI by decreasing pyroptosis, apoptosis and necroptosis of neurons, polarization of microglia/macrophages, and inflammation.

Study Duration

Not specified

Participants

42 male Sprague‒Dawley rats (200–220 g weight)

Evidence Level

Level 2: Animal Study

Key Findings

1
H2S ameliorated spinal cord neuron loss, prevented motor dysfunction after SCIRI, and exerted a neuroprotective effect via the inhibition of PANoptosis and overactivated microglia-mediated neuroinflammation in SCIRI.
2
The results showed that GYY4137 (a slow-releasing H2S donor) treatment attenuated the loss of Nissl bodies after SCIRI and improved the BBB score.
3
H2S prevented SCIRI by inhibiting pyroptosis, apoptosis and necroptosis in neurons; and (c) H2S decreased M1 polarization of microglia/macrophages and inflammation after SCIRI.

Research Summary

This study demonstrated that H2S preserved spinal cord neuron loss, prevented motor dysfunction, reduced inflammatory responses and microglial M1 polarization, and exerted neuroprotective effects via inhibition of neuron pyroptosis, apoptosis, and necroptosis in rats with SCIRI. The major findings are summarized as follows: (a) H2S alleviated motor dysfunction and reduced neuron loss after SCIRI; (b) H2S prevented SCIRI by inhibiting pyroptosis, apoptosis and necroptosis in neurons; and (c) H2S decreased M1 polarization of microglia/macrophages and inflammation after SCIRI. In this study we identified the involvement of PANoptosis and showed the anti-PANoptosis effect of H2S in SCIRI, suggesting a potential application for slow-releasing H2S donors as a clinical neuroprotective drug and improving the outcome of patients.

Practical Implications

Therapeutic Potential

Slow-releasing H2S donors may be a potential clinical neuroprotective drug for SCIRI.

Novel Treatment Strategy

Targeting PANoptosis with H2S could be a new therapeutic approach for spinal cord injuries.

Improved Patient Outcomes

H2S treatment may improve motor function and reduce neuron loss in SCIRI patients.

Study Limitations

1
The study was conducted only on rats.
2
The exact mechanism of H2S in mediating microglia/macrophage polarization requires further study.
3
Innovative drug donors and microglia/macrophage-deficient mice are needed to explore the exact mechanism.

Your Feedback

Was this summary helpful?

Back to Neurology