High-Frequency Gastric Electrical Stimulation Selectively Remodels Nitrergic Neurons in the Gastric Antrum of Healthy Beagles

IF 3.7 3区医学 Q2 CLINICAL NEUROLOGY

Neuromodulation Pub Date : 2026-10-01 Epub Date: 2026-05-06 DOI:10.1016/j.neurom.2026.04.013

Bo Huang MB, Mingyu Fu MS, Heer Yang MB, Xueqian Yang MB, Xin Wu MD, Yang Zhao MD, Guijun Fei MD, Jianing Li MD, Chunhua Hu PhD, Pan Tang MS, Xiucai Fang MD

{"title":"High-Frequency Gastric Electrical Stimulation Selectively Remodels Nitrergic Neurons in the Gastric Antrum of Healthy Beagles","authors":"Bo Huang MB, Mingyu Fu MS, Heer Yang MB, Xueqian Yang MB, Xin Wu MD, Yang Zhao MD, Guijun Fei MD, Jianing Li MD, Chunhua Hu PhD, Pan Tang MS, Xiucai Fang MD","doi":"10.1016/j.neurom.2026.04.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>The study aimed to investigate the effects and mechanisms of high-frequency short-pulse gastric electrical stimulation (GES) on gastric emptying and specific myenteric neurons of the gastric antrum in healthy beagle dogs.</div></div><div><h3>Materials and Methods</h3><div>Four healthy adult dogs were implanted with gastric electrical devices, randomly divided into two groups, and given high-frequency short-pulse GES and sham GES (SGES) separately for four weeks in a crossover design, with a three-week washout period. The GES parameters were set 5 mA, 15 Hz, 0.33 ms, cycle on 0.2 s and off 3 s, and the SGES group received no stimulation. Food and water intake, body weight, and gastric emptying scintigraphy were evaluated before and after stimulation. The total neurons, choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin (CALR)-immunoreactivity (IR) positive neurons were measured by indirect immunofluorescence double staining in the gastric antral specimens.</div></div><div><h3>Results</h3><div>After four weeks of GES, dogs were shown significantly higher relative food intake and water intake, along with greater median weight gain compared with the SGES group. GES produced no significant effect on gastric emptying. The total number of antral myenteric neurons in full-thickness biopsies remained comparable between two groups; the proportion of nNOS-IR neurons was significantly higher in GES group than in SGES group (34.9% ± 1.7% vs 27.8% ± 1.9%, <em>p</em> = 0.004). Conversely, the proportion of VIP-IR neurons was lower in GES group than in SGES group (62.5% ± 1.5% vs 65.0% ± 1.8%, <em>p</em> = 0.019). No significant differences were observed in the proportions of ChAT-IR or CALR-IR neurons.</div></div><div><h3>Conclusions</h3><div>High-frequency short-pulse GES selectively increased the proportion of gastric nitrergic (nNOS-IR) neurons and improved feeding tolerance without altering gastric emptying in healthy dogs. This finding indicates that inhibitory nitrergic neuronal remodeling constitutes a key mechanism underlying GES, probably enhancing gastric accommodation.</div></div>","PeriodicalId":19152,"journal":{"name":"Neuromodulation","volume":"29 7","pages":"Pages 1191-1199"},"PeriodicalIF":3.7000,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuromodulation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S109471592600111X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/5/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives

The study aimed to investigate the effects and mechanisms of high-frequency short-pulse gastric electrical stimulation (GES) on gastric emptying and specific myenteric neurons of the gastric antrum in healthy beagle dogs.

Materials and Methods

Four healthy adult dogs were implanted with gastric electrical devices, randomly divided into two groups, and given high-frequency short-pulse GES and sham GES (SGES) separately for four weeks in a crossover design, with a three-week washout period. The GES parameters were set 5 mA, 15 Hz, 0.33 ms, cycle on 0.2 s and off 3 s, and the SGES group received no stimulation. Food and water intake, body weight, and gastric emptying scintigraphy were evaluated before and after stimulation. The total neurons, choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin (CALR)-immunoreactivity (IR) positive neurons were measured by indirect immunofluorescence double staining in the gastric antral specimens.

Results

After four weeks of GES, dogs were shown significantly higher relative food intake and water intake, along with greater median weight gain compared with the SGES group. GES produced no significant effect on gastric emptying. The total number of antral myenteric neurons in full-thickness biopsies remained comparable between two groups; the proportion of nNOS-IR neurons was significantly higher in GES group than in SGES group (34.9% ± 1.7% vs 27.8% ± 1.9%, p = 0.004). Conversely, the proportion of VIP-IR neurons was lower in GES group than in SGES group (62.5% ± 1.5% vs 65.0% ± 1.8%, p = 0.019). No significant differences were observed in the proportions of ChAT-IR or CALR-IR neurons.

Conclusions

High-frequency short-pulse GES selectively increased the proportion of gastric nitrergic (nNOS-IR) neurons and improved feeding tolerance without altering gastric emptying in healthy dogs. This finding indicates that inhibitory nitrergic neuronal remodeling constitutes a key mechanism underlying GES, probably enhancing gastric accommodation.

查看原文本刊更多论文

高频胃电刺激对健康小猎犬胃窦氮能神经元的选择性重塑

目的：探讨高频短脉冲胃电刺激（GES）对健康比格犬胃排空和胃窦特异性肌肠神经元的影响及其机制。材料与方法：4只健康成年犬植入胃电装置，随机分为两组，采用交叉设计，分别给予高频短脉冲GES和假GES （SGES）治疗4周，洗脱期3周。设定GES参数为5 mA， 15 Hz, 0.33 ms，开0.2 s，关3 s， SGES组无刺激。在刺激前后评估食物和水的摄取量、体重和胃排空显示图。采用间接免疫荧光双染法测定胃窦总神经元、胆碱乙酰转移酶（ChAT）、血管活性肠肽（VIP）、神经元一氧化氮合酶（nNOS）和calretinin （CALR）免疫反应性（IR）阳性神经元的含量。结果：与SGES组相比，经过四周的GES后，狗的相对食物摄入量和水摄入量显著增加，中位体重增加也更大。GES对胃排空无显著影响。两组间全层活组织检查的心房肌间神经元总数保持可比性；GES组nNOS-IR神经元比例显著高于SGES组（34.9%±1.7% vs 27.8%±1.9%,p = 0.004）。相反，GES组VIP-IR神经元比例低于SGES组（62.5%±1.5% vs 65.0%±1.8%,p = 0.019）。ChAT-IR和CALR-IR神经元的比例无显著差异。结论：高频短脉冲GES选择性地增加了胃氮能（nNOS-IR）神经元的比例，并在不改变胃排空的情况下改善了摄食耐受性。这一发现表明，抑制性氮神经元重塑是GES的一个关键机制，可能会增强胃调节。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neuromodulation 医学-临床神经学

CiteScore

6.40

自引率

3.60%

发文量

978

审稿时长

54 days

期刊介绍： Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational, and basic science research in the field. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer-reviewed articles on the technology, science, and clinical application of devices that interface with the nervous system to treat disease and improve function.