Non-invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease
Non-invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease
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DOI：
10.1113/ep088848
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发表时间：
2021-02-17
影响因子：
2.7
通讯作者：
Shin, Damian S.
中科院分区：
文献类型：
--
作者：
Akhtar, Kainat;Hirschstein, Zall;Shin, Damian S.
新发现本研究的中心问题是什么？外周非侵入性聚焦超声靶向腹腔神经丛是否能改善炎症性肠病？主要发现及其重要性是什么？在溃疡性结肠炎大鼠模型中，靶向腹腔神经丛的外周非侵入性聚焦超声改善了粪便稠度并减少了粪便出血，这与没有聚焦超声治疗的动物相比，结肠更长，更健康。研究结果表明，这种新的神经调节技术可以作为一种合理的治疗方法，改善炎症性肠病（IBD）的症状。患有炎症性肠病（IBD）的个体的生活质量显着下降。在这里，我们的目标是刺激腹腔神经丛与非侵入性外周聚焦超声（FUS），以调节肠道胆碱能抗炎通路。鉴于这种疗法的非侵入性和靶向性质，这种方法可能具有作为有效IBD治疗的临床实用性。我们采用葡聚糖硫酸钠（DSS）结肠炎模型，在饮用水中给予大鼠较低（5%）和较高（7%）剂量。对患有严重IBD的大鼠每天两次连续12天给予腹腔神经丛FUS将粪便稠度评分从2.2 +/- 1改善至1.0 +/- 0.0，在第5天达到峰值功效，并且大体出血评分在第6天从1.8 +/-0.8最大程度地降低至0.8 +/- 0.8。在低剂量DSS组的动物中观察到类似的改善，这些动物仅接受FUS每日一次，持续12天。此外，每天接受两次FUS的高剂量DSS组的动物保持了结肠长度（17.7 +/- 2.5厘米），而饮用不含FUS的DSS的大鼠表现出明显的结肠损伤和缩短（13.8 +/- 0.6厘米），正如预期的那样。DSS降低了炎症细胞因子，如白细胞介素（IL）-1 β，IL-6，IL-17，肿瘤坏死因子-α和干扰素-γ，但与FUS后的对照水平一致，这可能是由于前者的结肠隐窝损失和后者的更健康的隐窝。最后，总的来说，这些结果表明外周神经节的非侵入性FUS可以提供精确的治疗以改善IBD病理学。
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.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)-1 beta, IL-6, IL-17, tumour necrosis factor-alpha and interferon-gamma 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.