Atalar Kerem, Alim Ece, Yigman Zeynep, Belen Hayrunnisa Bolay, Erten Fusun, Sahin Kazım, Soylu Ayse, Dizakar Saadet Ozen Akarca, Bahcelioglu Meltem
Department of Anatomy, Faculty of Medicine, Neuroscience and Neurotechnology Center of Excellence (NÖROM) and Neuropsychiatry Center, Gazi University, Ankara, Türkiye.
Department of Anatomy, Faculty of Medicine, Neuroscience and Neurotechnology Center of Excellence (NÖROM), Gazi University, Ankara, Türkiye.
J Anat. 2025 Apr;246(4):602-615. doi: 10.1111/joa.14178. Epub 2024 Dec 20.
Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a major health problem on a global scale and its treatment is unsatisfactory. We aimed to investigate the effects of transauricular vagal nerve stimulation (tVNS) on inflammation in rats with IBD induced by trinitrobenzene sulfonic acid (TNBS). A total of 36 adult female Sprague-Dawley rats were given TNBS, or vehicle, and tVNS, or sham, every other day for 30 min for 10 days. Postmortem macroscopic and microscopic colon morphology were evaluated by histological staining. Additionally, IL-1β, IL-6, IL-10, and TNF-α cytokine levels in the colon and the brain were evaluated by immunohistochemistry and western blotting analysis. TNBS induced epithelial damage, inflammation, ulceration, and thickened mucosal layer in the colonic tissues. Administration of tVNS significantly ameliorated the severity of TNBS-induced tissue damage and inflammatory response. TNBS also alters pro-inflammatory and anti-inflammatory balance in the brain tissue. TVNS application significantly suppressed the protein levels of pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF- α while augmenting the level of anti-inflammatory cytokine IL-10 in the colonic and the brain tissue. We have shown that TNBS-mediated colonic inflammation and tissue damage are associated with neuroinflammatory responses in the brain tissue. Also demonstrated for the first time that neuroinflammatory response in the gut-brain axis is suppressed by tVNS in the IBD model. Non-invasive tVNS stands out as a new potential treatment option for types of IBD.
炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），是一个全球性的重大健康问题，其治疗效果并不理想。我们旨在研究经耳迷走神经刺激（tVNS）对三硝基苯磺酸（TNBS）诱导的IBD大鼠炎症的影响。总共36只成年雌性Sprague-Dawley大鼠被给予TNBS或赋形剂，以及tVNS或假刺激，每隔一天进行30分钟，共10天。通过组织学染色评估死后结肠的宏观和微观形态。此外，通过免疫组织化学和蛋白质印迹分析评估结肠和大脑中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和肿瘤坏死因子-α（TNF-α）细胞因子水平。TNBS诱导结肠组织上皮损伤、炎症、溃疡和黏膜层增厚。给予tVNS显著改善了TNBS诱导的组织损伤和炎症反应的严重程度。TNBS还改变了脑组织中促炎和抗炎的平衡。应用tVNS显著抑制了促炎细胞因子IL-1β、IL-6和TNF-α的蛋白水平，同时提高了结肠和脑组织中抗炎细胞因子IL-10的水平。我们已经表明，TNBS介导的结肠炎症和组织损伤与脑组织中的神经炎症反应有关。同时首次证明，在IBD模型中，tVNS可抑制肠-脑轴中的神经炎症反应。非侵入性tVNS作为一种新的潜在治疗方法，在IBD的治疗中脱颖而出。
