Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans
Focused ultrasound stimulation (FUS) activates mechanosensitive ion channels and is emerging as a method of noninvasive neuromodulation. In preclinical studies, FUS of the spleen (sFUS) activates an anti-inflammatory neural pathway which suppresses acute and chronic inflammation. However, the releva...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X23017436 |
| _version_ | 1797798095546744832 |
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| author | Stavros Zanos Despoina Ntiloudi John Pellerito Richard Ramdeo John Graf Kirk Wallace Victoria Cotero Jeff Ashe Jessica Moon Meghan Addorisio David Shoudy Thomas R. Coleman Michael Brines Chris Puleo Kevin J. Tracey Sangeeta S. Chavan |
| author_facet | Stavros Zanos Despoina Ntiloudi John Pellerito Richard Ramdeo John Graf Kirk Wallace Victoria Cotero Jeff Ashe Jessica Moon Meghan Addorisio David Shoudy Thomas R. Coleman Michael Brines Chris Puleo Kevin J. Tracey Sangeeta S. Chavan |
| author_sort | Stavros Zanos |
| collection | DOAJ |
| description | Focused ultrasound stimulation (FUS) activates mechanosensitive ion channels and is emerging as a method of noninvasive neuromodulation. In preclinical studies, FUS of the spleen (sFUS) activates an anti-inflammatory neural pathway which suppresses acute and chronic inflammation. However, the relevance of sFUS for regulating inflammatory responses in humans is unknown. Here, we used a modified diagnostic ultrasound imaging system to target the spleen of healthy human subjects with 3 min of continuously swept or stationary focused pulsed ultrasound, delivered at three different energy levels within allowable safety exposure limits. Potential anti-inflammatory effects of sFUS were assessed by measuring sFUS-elicited changes in endotoxin-induced tumor necrosis factor (TNF) production in whole blood samples from insonified subjects. We found that stimulation with either continuously swept or focused pulsed ultrasound has an anti-inflammatory effect: sFUS lowers TNF production for >2 h, with TNF returning to baseline by 24 h following sFUS. This response is independent of anatomical target (i.e., spleen hilum or parenchyma) or ultrasound energy level. No clinical, biochemical, or hematological parameters are adversely impacted. This is the first demonstration that sFUS suppresses the normal inflammatory response in humans, with potential implications for noninvasive bioelectronic therapy of inflammatory disorders. |
| first_indexed | 2024-03-13T03:59:20Z |
| format | Article |
| id | doaj.art-be0515c41a95436fa5b189fda07edc16 |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-03-13T03:59:20Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-be0515c41a95436fa5b189fda07edc162023-06-22T05:02:39ZengElsevierBrain Stimulation1935-861X2023-05-01163703711Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humansStavros Zanos0Despoina Ntiloudi1John Pellerito2Richard Ramdeo3John Graf4Kirk Wallace5Victoria Cotero6Jeff Ashe7Jessica Moon8Meghan Addorisio9David Shoudy10Thomas R. Coleman11Michael Brines12Chris Puleo13Kevin J. Tracey14Sangeeta S. Chavan15Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Corresponding author. Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USA.Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USADonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Radiology, Northwell Health, Manhasset, NY, 11030, USAInstitute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USAGeneral Electric (GE) Research, Niskayuna, NY, USA, 12309General Electric (GE) Research, Niskayuna, NY, USA, 12309General Electric (GE) Research, Niskayuna, NY, USA, 12309General Electric (GE) Research, Niskayuna, NY, USA, 12309Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USAInstitute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USAGeneral Electric (GE) Research, Niskayuna, NY, USA, 12309Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USAInstitute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USAGeneral Electric (GE) Research, Niskayuna, NY, USA, 12309Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USAInstitute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USA; Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Corresponding author. Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, 11030, USA.Focused ultrasound stimulation (FUS) activates mechanosensitive ion channels and is emerging as a method of noninvasive neuromodulation. In preclinical studies, FUS of the spleen (sFUS) activates an anti-inflammatory neural pathway which suppresses acute and chronic inflammation. However, the relevance of sFUS for regulating inflammatory responses in humans is unknown. Here, we used a modified diagnostic ultrasound imaging system to target the spleen of healthy human subjects with 3 min of continuously swept or stationary focused pulsed ultrasound, delivered at three different energy levels within allowable safety exposure limits. Potential anti-inflammatory effects of sFUS were assessed by measuring sFUS-elicited changes in endotoxin-induced tumor necrosis factor (TNF) production in whole blood samples from insonified subjects. We found that stimulation with either continuously swept or focused pulsed ultrasound has an anti-inflammatory effect: sFUS lowers TNF production for >2 h, with TNF returning to baseline by 24 h following sFUS. This response is independent of anatomical target (i.e., spleen hilum or parenchyma) or ultrasound energy level. No clinical, biochemical, or hematological parameters are adversely impacted. This is the first demonstration that sFUS suppresses the normal inflammatory response in humans, with potential implications for noninvasive bioelectronic therapy of inflammatory disorders.http://www.sciencedirect.com/science/article/pii/S1935861X23017436InflammationCytokinesUltrasoundSpleenCholinergic anti-inflammatory pathwayBioelectronic medicine |
| spellingShingle | Stavros Zanos Despoina Ntiloudi John Pellerito Richard Ramdeo John Graf Kirk Wallace Victoria Cotero Jeff Ashe Jessica Moon Meghan Addorisio David Shoudy Thomas R. Coleman Michael Brines Chris Puleo Kevin J. Tracey Sangeeta S. Chavan Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans Brain Stimulation Inflammation Cytokines Ultrasound Spleen Cholinergic anti-inflammatory pathway Bioelectronic medicine |
| title | Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans |
| title_full | Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans |
| title_fullStr | Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans |
| title_full_unstemmed | Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans |
| title_short | Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans |
| title_sort | focused ultrasound neuromodulation of the spleen activates an anti inflammatory response in humans |
| topic | Inflammation Cytokines Ultrasound Spleen Cholinergic anti-inflammatory pathway Bioelectronic medicine |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X23017436 |
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