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Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

ABSTRACT: Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen significantly reduces disease severity in a mouse model of inflammatory arthritis. Improvements are observed only with specific parameters, in which US can provide both protective and therapeutic effects. Single cell RNA sequencing of splenocytes and experiments in genetically-immunodeficient mice reveal the importance of both T and B cell populations in the anti-inflammatory pathway. These findings demonstrate the potential for US stimulation of the spleen to treat inflammatory diseases.

SUBMITTER: Zachs DP

PROVIDER: S-EPMC6414603 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

Zachs Daniel P DP Offutt Sarah J SJ Graham Rachel S RS Kim Yohan Y Mueller Jerel J Auger Jennifer L JL Schuldt Nathaniel J NJ Kaiser Claire R W CRW Heiller Abigail P AP Dutta Raini R Guo Hongsun H Alford Jamu K JK Binstadt Bryce A BA Lim Hubert H HH

Nature communications 20190312 1

Targeted noninvasive control of the nervous system and end-organs may enable safer and more effective treatment of multiple diseases compared to invasive devices or systemic medications. One target is the cholinergic anti-inflammatory pathway that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis. Here we report that daily noninvasive ultrasound (US) stimulation targeting the spleen sign ...[more]

PMID: 30862842

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Project description:BackgroundMultiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD.MethodsBy employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS.DiscussionSome limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD.Trial registrationThis trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023.

Dataset Information

Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

Publications

Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis.

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