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Related Experiment Video

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Splenic Nerve Neuromodulation Reduces Inflammation and Promotes Resolution in Chronically Implanted Pigs.

David M Sokal1, Alex McSloy2, Matteo Donegà1

  • 1Translation and Engineering, Galvani Bioelectronics, Stevenage, United Kingdom.

Frontiers in Immunology
|April 16, 2021
PubMed
Summary

Neuromodulation of the splenic nerve in conscious pigs reduced inflammatory markers and promoted immune resolution. This chronic stimulation via implanted devices is safe and effective for potential clinical use.

Keywords:
autonomic nervous systembioelectronic medicineendotoxemiainflammationneuromodulationspecialized pro resolving mediatorssplenic nervestimulation

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Area of Science:

  • Neuroimmunology
  • Translational Medicine
  • Surgical Innovation

Background:

  • Neuromodulation of the immune system offers a novel therapeutic approach for inflammatory diseases.
  • Previous studies demonstrated splenic nerve stimulation's anti-inflammatory effects in anesthetized animals.
  • Chronic efficacy and safety testing in a large animal model are crucial for clinical translation.

Purpose of the Study:

  • To evaluate the chronic effects and safety of conscious splenic nerve neuromodulation in a large animal model.
  • To refine stimulation parameters for efficient splenic nerve activation with minimal cardiovascular impact.
  • To assess the immunomodulatory and pro-resolving effects of long-term splenic nerve stimulation.

Main Methods:

  • Minimally invasive laparoscopic implantation of a cuff electrode and pulse generator around the splenic neurovascular bundle in pigs.
  • Refinement of clinically-relevant stimulation parameters for conscious, freely-behaving animals.
  • Assessment of inflammatory markers (TNF-α), monocyte populations, lipid mediators, and nerve integrity post-stimulation.

Main Results:

  • Daily splenic nerve neuromodulation was well-tolerated in freely-behaving pigs.
  • Significant reduction in circulating tumor necrosis factor alpha and pro-inflammatory monocytes observed.
  • Increased concentration of specialized pro-resolving mediators and decreased pro-inflammatory eicosanoids detected.
  • Splenic nerve integrity was maintained up to 70 days post-implantation.

Conclusions:

  • Chronic splenic nerve neuromodulation using implanted electronics is safe and well-tolerated.
  • This therapy effectively modulates the immune system towards a less inflammatory, pro-resolving phenotype.
  • These findings support the potential of splenic nerve neuromodulation as a clinical strategy for inflammatory conditions.