Electrical stimulation of gut motility guided by an in silico model.
Electrical stimulation of gut motility guided by an in silico model.
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DOI：
10.1088/1741-2552/aa86c8
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发表时间：
2017-12
影响因子：
4
通讯作者：
Shen X
中科院分区：
文献类型：
--
作者：
Barth BB;Henriquez CS;Grill WM;Shen X
中枢和周围神经系统的神经调节对于治疗从帕金森病、癫痫到慢性疼痛等多种疾病变得越来越重要。然而，胃肠道（GI）的神经调节在治疗影响大量人群的功能性胃肠道疾病方面取得的成功相对有限，因为刺激对肠神经系统（ENS）和肠道动力的影响尚不清楚。在这里，我们开发了 ENS 的综合神经力学模型，并评估了增强肠道蠕动的神经刺激策略，并通过体内实验进行了验证。该计算模型包括肠神经元、平滑肌纤维和卡哈尔间质细胞的网络，这些细胞在肠道运动模型中调节虚拟颗粒的推进。对 ENS 介导的运动的模拟细胞外刺激表明，0.5 Hz 的正弦电流比常用于神经调节治疗的传统高频矩形电流脉冲更能有效地增加内在蠕动和减少结肠传输时间。对模型的进一步分析表明，0.5 Hz 正弦电流在调节 Cajal 间质细胞的起搏器频率方面更有效。为了测试模型的预测，我们对远端结肠进行体内电刺激，同时测量清醒大鼠的珠子推进力。实验结果证实，0.5 Hz 正弦电流比高频脉冲更能有效增强肠道蠕动。这项工作展示了一种能够优化胃肠道神经调节参数的计算机胃肠道神经肌肉模型，并表明低频正弦电流可以提高胃肠道起搏的功效。
Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases—ranging from Parkinson’s Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood. Here we develop an integrated neuromechanical model of the ENS and assess neurostimulation strategies for enhancing gut motility, validated by in vivo experiments. The computational model included a network of enteric neurons, smooth muscle fibers, and interstitial cells of Cajal, which regulated propulsion of a virtual pellet in a model of gut motility. Simulated extracellular stimulation of ENS-mediated motility revealed that sinusoidal current at 0.5 Hz was more effective at increasing intrinsic peristalsis and reducing colon transit time than conventional higher frequency rectangular current pulses, as commonly used for neuromodulation therapy. Further analysis of the model revealed that the 0.5 Hz sinusoidal currents were more effective at modulating the pacemaker frequency of interstitial cells of Cajal. To test the predictions of the model, we conducted in vivo electrical stimulation of the distal colon while measuring bead propulsion in awake rats. Experimental results confirmed that 0.5 Hz sinusoidal currents were more effective than higher frequency pulses at enhancing gut motility. This work demonstrates an in silico GI neuromuscular model to enable GI neuromodulation parameter optimization and suggests that low frequency sinusoidal currents may improve the efficacy of GI pacing.