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  4. Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-­In-­Human Results of Shock Wave Therapy Prove Safety and Feasibility

Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-­In-­Human Results of Shock Wave Therapy Prove Safety and Feasibility

Journal of the American Heart Association, 2022 · DOI: 10.1161/JAHA.122.026076 · Published: January 1, 2022

Regenerative MedicineNeurologySurgery

Simple Explanation

Spinal cord ischemia (SCI) is a serious complication after aortic surgery, leading to nerve cell damage and limited treatment options. This study explores shock wave therapy (SWT) as a potential treatment. The researchers found that SWT can reduce oxidative stress and cell death in nerve cells damaged by ischemia. This is achieved through the activation of a protective factor called NRF2 and the involvement of the immune receptor TLR3. In a small group of patients with SCI, SWT was shown to be safe and feasible. The study suggests that SWT could become a valuable regenerative treatment for SCI.

Study Duration
6 months follow-up
Participants
5 patients with spinal cord ischemia
Evidence Level
Level 4; First-in-human study

Key Findings

  • 1
    SWT reduces reactive oxygen species and apoptosis in human neurons subjected to ischemic injury.
  • 2
    SWT induces the expression of NRF2 protein and mRNA levels in a TLR3-dependent manner, protecting against oxidative damage.
  • 3
    In a first-in-human study, SWT was found to be safe and feasible in patients with SCI, with some improvement in neurological scores.

Research Summary

This study investigates the potential of shock wave therapy (SWT) to mitigate spinal cord ischemia (SCI) following aortic surgery. The research includes in vitro experiments on human neurons, in vivo studies on zebrafish, and a first-in-human application on five SCI patients. The preclinical results demonstrate that SWT reduces oxidative damage and neuronal apoptosis via the NRF2 pathway and TLR3. Studies in zebrafish further support the evolutionary conservation of TLR3-mediated spinal cord regeneration. The first-in-human application of SWT proves its safety and feasibility in SCI patients, suggesting it as a potential regenerative treatment option, though the study acknowledges its limitations as a small, non-randomized trial.

Practical Implications

Potential Therapeutic Approach

SWT could serve as a novel therapeutic approach to reduce oxidative damage and secondary neuronal damage in patients with SCI.

Future Clinical Trials

The findings support the need for prospective randomized-controlled trials to further investigate the efficacy of SWT in SCI patients.

Early Diagnosis Importance

Highlights the significance of early SCI diagnosis using methods like near-infrared spectroscopy to improve patient outcomes with SWT intervention.

Study Limitations

  • 1
    Small sample size limits generalizability
  • 2
    Heterogeneity of SCI patients (varied lesion characteristics)
  • 3
    Treatment was administered at relatively late time-points after ischemic injury onset

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