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Phrenic nerve stimulation mitigates hippocampal and brainstem inflammation in an ARDS model
Thiago G Bassi1, Elizabeth C Rohrs2,3, Karl C Fernandez3,4
1Lungpacer Medical Inc., Vancouver, BC, Canada.
Frontiers in Physiology
|May 22, 2023
Summary
Phrenic nerve stimulation (PNS) with mechanical ventilation (MV) in pigs with acute respiratory distress syndrome (ARDS) reduced brain inflammation. PNS on every breath mitigated hippocampal and brainstem inflammatory markers compared to MV alone.
Area of Science:
- Neuroscience
- Critical Care Medicine
- Pulmonary Medicine
Background:
- Mechanical ventilation (MV) in acute respiratory distress syndrome (ARDS) can lead to neuroinflammation.
- Phrenic nerve stimulation (PNS) has shown potential in reducing neuroinflammation in ARDS models.
Purpose of the Study:
- To investigate the effects of PNS combined with MV on hippocampal and brainstem inflammatory and synaptic markers in an ARDS porcine model.
- To compare the impact of PNS applied every other breath versus every breath during MV.
Main Methods:
- A moderate ARDS porcine model was created using oleic acid infusion.
- Three groups were studied: MV alone, MV + PNS every other breath, and MV + PNS every breath for 12 hours.
- Tissue concentrations of inflammatory markers (e.g., IL-1β, IL-8, IFN-γ) and synaptic markers (e.g., synaptophysin, N-methyl-D-aspartate receptors) in the hippocampus and brainstem were measured.
Main Results:
- The MV + PNS every breath group showed increased hippocampal concentrations of GM-CSF, N-methyl-D-aspartate receptor 2B, and synaptophysin compared to MV alone.
- The MV + PNS every breath group exhibited lower brainstem concentrations of IL-1β and IL-8, but higher concentrations of IFN-γ and N-methyl-D-aspartate receptor 2A compared to MV alone.
Conclusions:
- Mechanical ventilation in ARDS is associated with hippocampal and brainstem inflammation.
- Phrenic nerve stimulation applied with every breath during MV can mitigate this inflammation in a moderate ARDS porcine model.

