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  1. Article ; Online: Accelerating cutaneous healing in a rodent model of type II diabetes utilizing non-invasive focused ultrasound targeted at the spleen

    Christine Morton / Victoria Cotero / Jeffrey Ashe / Fiona Ginty / Christopher Puleo

    Frontiers in Neuroscience, Vol

    2022  Volume 16

    Abstract: Healing of wounds is delayed in Type 2 Diabetes Mellitus (T2DM), and new treatment approaches are urgently needed. Our earlier work showed that splenic pulsed focused ultrasound (pFUS) alters inflammatory cytokines in models of acute endotoxemia and ... ...

    Abstract Healing of wounds is delayed in Type 2 Diabetes Mellitus (T2DM), and new treatment approaches are urgently needed. Our earlier work showed that splenic pulsed focused ultrasound (pFUS) alters inflammatory cytokines in models of acute endotoxemia and pneumonia via modulation of the cholinergic anti-inflammatory pathway (CAP) (ref below). Based on these earlier results, we hypothesized that daily splenic exposure to pFUS during wound healing would accelerate closure rate via altered systemic cytokine titers. In this study, we applied non-invasive ultrasound directed to the spleen of a rodent model [Zucker Diabetic Sprague Dawley (ZDSD) rats] of T2DM with full thickness cutaneous excisional wounds in an attempt to accelerate wound healing via normalization of T2DM-driven aberrant cytokine expression. Daily (1x/day, Monday-Friday) pFUS pulses were targeted externally to the spleen area for 3 min over the course of 15 days. Wound diameter was measured daily, and levels of cytokines were evaluated in spleen and wound bed lysates. Non-invasive splenic pFUS accelerated wound closure by up to 4.5 days vs. sham controls. The time to heal in all treated groups was comparable to that of healthy rats from previously published studies (ref below), suggesting that the pFUS treatment restored a normal wound healing phenotype to the ZDSD rats. IL-6 was lower in stimulated spleen (-2.24 ± 0.81 Log2FC, p = 0.02) while L-selectin was higher in the wound bed of stimulated rodents (2.53 ± 0.72 Log2FC, p = 0.003). In summary, splenic pFUS accelerates healing in a T2DM rat model, demonstrating the potential of the method to provide a novel, non-invasive approach for wound care in diabetes.
    Keywords bioelectronic medicine ; nerve stimulation ; neuromodulation ; therapy ; ultrasound ; wound care ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
    Subject code 630
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions

    Tomás S. Huerta / Alex Devarajan / Tea Tsaava / Arvind Rishi / Victoria Cotero / Christopher Puleo / Jeffrey Ashe / Thomas R. Coleman / Eric H. Chang / Kevin J. Tracey / Sangeeta S. Chavan

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Abstract Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an ... ...

    Abstract Abstract Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate “Western” diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Evidence of Long-range nerve pathways connecting and coordinating activity in secondary lymph organs

    Victoria Cotero / Tzu-Jen Kao / John Graf / Jeffrey Ashe / Christine Morton / Sangeeta S. Chavan / Stavros Zanos / Kevin J. Tracey / Christopher M. Puleo

    Bioelectronic Medicine, Vol 6, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract Background Peripheral nerve reflexes enable organ systems to maintain long-term physiological homeostasis while responding to rapidly changing environmental conditions. Electrical nerve stimulation is commonly used to activate these reflexes and ...

    Abstract Abstract Background Peripheral nerve reflexes enable organ systems to maintain long-term physiological homeostasis while responding to rapidly changing environmental conditions. Electrical nerve stimulation is commonly used to activate these reflexes and modulate organ function, giving rise to an emerging class of therapeutics called bioelectronic medicines. Dogma maintains that immune cell migration to and from organs is mediated by inflammatory signals (i.e. cytokines or pathogen associated signaling molecules). However, nerve reflexes that regulate immune function have only recently been elucidated, and stimulation of these reflexes for therapeutic effect has not been fully investigated. Methods We utilized both electrical and ultrasound-based nerve stimulation to activate nerve pathways projecting to specific lymph nodes. Tissue and cell analysis of the stimulated lymph node, distal lymph nodes and immune organs is then utilized to measure the stimulation-induced changes in neurotransmitter/neuropeptide concentrations and immune cellularity in each of these sites. Results and conclusions In this report, we demonstrate that activation of nerves and stimulated release of neurotransmitters within a local lymph node results in transient retention of immune cells (e.g. lymphocytes and neutrophils) at that location. Furthermore, such stimulation results in transient changes in neurotransmitter concentrations at distal organs of the immune system, spleen and liver, and mobilization of immune cells into the circulation. This report will enable future studies in which stimulation of these long-range nerve connections between lymphatic and immune organs can be applied for clinical purpose, including therapeutic modulation of cellularity during vaccination, active allergic response, or active auto-immune disease.
    Keywords Neuromodulation ; Bioelectronic medicine ; Immunology ; Neuroscience ; Neural immune reflexes ; Biomedical engineering ; Medical technology ; R855-855.5
    Subject code 610
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Author Correction

    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

    Nature Communications, Vol 11, Iss 1, Pp 1-

    Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Author Correction

    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

    Nature Communications, Vol 11, Iss 1, Pp 1-

    Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation

    2020  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Science ; Q
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: 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

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be ... ...

    Abstract Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.
    Keywords Science ; Q
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: 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

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be ... ...

    Abstract Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.
    Keywords Science ; Q
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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