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Non‐invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease
Author(s) -
Akhtar Kainat,
Hirschstein Zall,
Stefanelli Allison,
Iannilli Emilia,
Srinivasan Aditya,
Barenboim Linda,
Balkaya Mustafa,
Cunha Alexandra,
Audil Aliyah,
Kochman Eliyahu M.,
Chua Fuyee,
Ravi Maya,
Mikkilineni Saisree,
Watkins Hanel,
O'Connor William,
Fan Ying,
Cotero Victoria,
Ashe Jeffrey,
Puleo Christopher,
Kao TzuJen,
Shin Damian S.
Publication year - 2021
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep088848
Subject(s) - medicine , inflammatory bowel disease , ulcerative colitis , gastroenterology , neuromodulation , ultrasound , disease , colitis , myenteric plexus , radiology , central nervous system , immunohistochemistry
New FindingsWhat 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.Abstract 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.