Characterization of idiopathic chronic diarrhea and associated intestinal inflammation and preliminary observations of effects of vagal nerve stimulation in a non-human primate.

Autor: Populin LC; Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Rajala AZ; Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Matkowskyj KA; Department of Pathology & Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Saha S; Division of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA., Zeng W; Department of Surgery, Dental and Plastic Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Christian B; Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., McVea A; Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Tay EX; Department of Anatomy, Physiology and Cell Biology, UC Davis, Davis, California, USA., Mueller EM; Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Malone ME; Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Brust-Mascher I; Department of Anatomy, Physiology and Cell Biology, UC Davis, Davis, California, USA., McMillan AB; Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Department of Radiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Ludwig KA; Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Suminski AJ; Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA., Reardon C; Department of Anatomy, Physiology and Cell Biology, UC Davis, Davis, California, USA., Furness JB; Department of Anatomy & Physiology, University of Melbourne, Parkville, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2024 Sep; Vol. 36 (9), pp. e14876. Date of Electronic Publication: 2024 Jul 27.
DOI: 10.1111/nmo.14876
Abstrakt: Background: Diarrhea is commonly associated with irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, and other gastrointestinal dysfunctions. Spontaneously occurring idiopathic chronic diarrhea is frequent in rhesus macaques, but has not been used as a model for the investigation of diarrhea or its treatment. We characterized this condition and present preliminary data demonstrating that left vagal nerve stimulation provides relief.
Methods: Stool consistency scores were followed for up to 12 years. Inflammation was assessed by plasma C-reactive protein, [ 18 F]fluorodeoxyglucose (FDG) uptake, measured by positron emission tomography (PET), multiplex T cell localization, endoscopy and histology. The vagus was stimulated for 9 weeks in conscious macaques, using fully implanted electrodes, under wireless control.
Key Results: Macaques exhibited recurrent periods of diarrhea for up to 12 years, and signs of inflammation: elevated plasma C-reactive protein, increased bowel FDG uptake and increased mucosal T helper1 T-cells. The colon and distal ileum were endoscopically normal, and histology revealed mild colonic inflammation. Application of vagal nerve stimulation to conscious macaques (10 Hz, 30 s every 3 h; 24 h a day for 9 weeks) significantly reduced severity of diarrhea and also reduced inflammation, as measured by FDG uptake and C-reactive protein.
Conclusions and Inferences: These macaques exhibit spontaneously occurring diarrhea with intestinal inflammation that can be reduced by VNS. The data demonstrate the utility of this naturally occurring primate model to study the physiology and treatments for chronic diarrhea and the neural control circuits influencing diarrhea and inflammation that are not accessible in human subjects.
(© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: