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Nature communications
03 12, 2019;10 (1): 952.

Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation.

Victoria Cotero, Ying Fan, Tea Tsaava, Adam M Kressel, Ileana Hancu, Paul Fitzgerald, Kirk Wallace, Sireesha Kaanumalle, John Graf, Wayne Rigby, Tzu-Jen Kao, Jeanette Roberts, Chitresh Bhushan, Suresh Joel, Thomas R Coleman, Stavros Zanos, Kevin J Tracey, Jeffrey Ashe, Sangeeta S Chavan, Christopher Puleo
Author Information
  1. Victoria Cotero: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  2. Ying Fan: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  3. Tea Tsaava: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  4. Adam M Kressel: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  5. Ileana Hancu: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  6. Paul Fitzgerald: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  7. Kirk Wallace: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  8. Sireesha Kaanumalle: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  9. John Graf: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  10. Wayne Rigby: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  11. Tzu-Jen Kao: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  12. Jeanette Roberts: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  13. Chitresh Bhushan: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  14. Suresh Joel: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  15. Thomas R Coleman: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  16. Stavros Zanos: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  17. Kevin J Tracey: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  18. Jeffrey Ashe: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA.
  19. Sangeeta S Chavan: Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY, 11020, USA.
  20. Christopher Puleo: GE Global Research Center, 1 Research Circle, Niskayuna, NY, 12309, USA. puleo@ge.com.
PMID: 30862827 DOI: 10.1038/s41467-019-08750-9

Abstract

Tools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS). Next, hepatic U/S stimulation is shown to modulate pathways that regulate blood glucose and is as effective as VNS in suppressing the hyperglycemic effect of endotoxin exposure. This response to hepatic U/S is only found when targeting specific sub-organ locations known to contain glucose sensory neurons, and both molecular (i.e. neurotransmitter concentration and cFOS expression) and neuroimaging results indicate US induced signaling to metabolism-related hypothalamic sub-nuclei. These data demonstrate that U/S stimulation within organs provides a new method for site-selective neuromodulation to regulate specific physiological functions.

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Grants

  1. R35 GM118182/NIGMS NIH HHS

MeSH Term

Animals
Liver
Magnetic Resonance Imaging
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Neural Pathways
Neuroimmunomodulation
Organ Specificity
Rats
Rats, Sprague-Dawley
Spleen
Ultrasonic Therapy
Vagus Nerve Stimulation
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Article has an altmetric score of 95

Word Cloud

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