Non-invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease.

Crohn's disease IBD bioelectric medicine celiac plexus dextran sulfate sodium medical device peripheral ganglion superior mesenteric plexus ulcerative colitis

Journal

Experimental physiology
ISSN: 1469-445X
Titre abrégé: Exp Physiol
Pays: England
ID NLM: 9002940

Informations de publication

Date de publication:
04 2021
Historique:
received: 15 06 2020
accepted: 26 01 2021
pubmed: 30 1 2021
medline: 1 4 2022
entrez: 29 1 2021
Statut: ppublish

Résumé

What is the central question of this study? Does peripheral non-invasive focused ultrasound targeted to the celiac plexus improve inflammatory bowel disease? What is the main finding and its importance? Peripheral non-invasive focused ultrasound targeted to the celiac plexus in a rat model of ulcerative colitis improved stool consistency and reduced stool bloodiness, which coincided with a longer and healthier colon than in animals without focused ultrasound treatment. The findings suggest that this novel neuromodulatory technology could serve as a plausible therapeutic approach for improving symptoms of inflammatory bowel disease. Individuals suffering from inflammatory bowel disease (IBD) experience significantly diminished quality of life. Here, we aim to stimulate the celiac plexus with non-invasive peripheral focused ultrasound (FUS) to modulate the enteric cholinergic anti-inflammatory pathway. This approach may have clinical utility as an efficacious IBD treatment given the non-invasive and targeted nature of this therapy. We employed the dextran sodium sulfate (DSS) model of colitis, administering lower (5%) and higher (7%) doses to rats in drinking water. FUS on the celiac plexus administered twice a day for 12 consecutive days to rats with severe IBD improved stool consistency scores from 2.2 ± 1 to 1.0 ± 0.0 with peak efficacy on day 5 and maximum reduction in gross bleeding scores from 1.8 ± 0.8 to 0.8 ± 0.8 on day 6. Similar improvements were seen in animals in the low dose DSS group, who received FUS only once daily for 12 days. Moreover, animals in the high dose DSS group receiving FUS twice daily maintained colon length (17.7 ± 2.5 cm), while rats drinking DSS without FUS exhibited marked damage and shortening of the colon (13.8 ± 0.6 cm) as expected. Inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-17, tumour necrosis factor-α and interferon-γ were reduced with DSS but coincided with control levels after FUS, which is plausibly due to a loss of colon crypts in the former and healthier crypts in the latter. Lastly, overall, these results suggest non-invasive FUS of peripheral ganglion can deliver precision therapy to improve IBD symptomology.

Identifiants

pubmed: 33512049
doi: 10.1113/EP088848
doi:

Substances chimiques

Cytokines 0
Dextran Sulfate 9042-14-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1038-1060

Informations de copyright

© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.

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Auteurs

Kainat Akhtar (K)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Zall Hirschstein (Z)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Allison Stefanelli (A)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Emilia Iannilli (E)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Aditya Srinivasan (A)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Linda Barenboim (L)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Mustafa Balkaya (M)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Alexandra Cunha (A)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Aliyah Audil (A)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Eliyahu M Kochman (EM)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Fuyee Chua (F)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Maya Ravi (M)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Saisree Mikkilineni (S)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Hanel Watkins (H)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

William O'Connor (W)

Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, USA.

Ying Fan (Y)

General Electric Global Research Center, Niskayuna, NY, USA.

Victoria Cotero (V)

General Electric Global Research Center, Niskayuna, NY, USA.

Jeffrey Ashe (J)

General Electric Global Research Center, Niskayuna, NY, USA.

Christopher Puleo (C)

General Electric Global Research Center, Niskayuna, NY, USA.

Tzu-Jen Kao (TJ)

General Electric Global Research Center, Niskayuna, NY, USA.

Damian S Shin (DS)

Department of Neuroscience & Experimental Therapeutics, Albany Medical College, Albany, NY, USA.
Department of Neurology, Albany Medical Center, Albany, NY, USA.

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