Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.
Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis.
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DOI：
10.1371/journal.pone.0104530
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tak PP
中科院分区：
文献类型：
--
作者：
Levine YA;Koopman FA;Faltys M;Caravaca A;Bendele A;Zitnik R;Vervoordeldonk MJ;Tak PP
炎症反射是神经系统通过调节先天免疫和适应性免疫来维持免疫稳态的生理机制。我们推测，反射可能是利用治疗，以减少病理水平的炎症类风湿性关节炎，通过激活其原型传出臂，称为胆碱能抗炎通路。为了探索这一点，我们确定了胆碱能抗炎通路的电神经刺激是否降低了胶原诱导的关节炎模型中疾病的严重程度。植入迷走神经袖状电极的大鼠诱导胶原诱导性关节炎，并随访15天。从第9天到研究结束，动物每天接受一次主动或假电刺激。评估关节肿胀、组织学、细胞因子和骨代谢介质水平。与假手术治疗相比，胆碱能抗炎通路的主动神经刺激导致踝关节直径减少52%（p = 0.02），踝关节直径减少57%（曲线下面积; p = 0.02）和总体组织学关节炎评分减少46%（p = 0.01），炎症、血管翳形成、软骨破坏和骨侵蚀显著改善（p = 0.02），伴随全身细胞因子水平的数值降低，未达到统计学显著性。 骨侵蚀改善与血清NF-κB配体受体激活剂（RANKL）水平从132±13 pg/mL降至6±2 pg/mL相关（平均值±SEM，p = 0.01）。 通过使用植入的迷走神经电刺激袖带电极递送胆碱能抗炎通路的神经刺激降低胶原诱导的关节炎的严重程度，并支持在人类炎症性疾病中测试该方法的基本原理。
The inflammatory reflex is a physiological mechanism through which the nervous system maintains immunologic homeostasis by modulating innate and adaptive immunity. We postulated that the reflex might be harnessed therapeutically to reduce pathological levels of inflammation in rheumatoid arthritis by activating its prototypical efferent arm, termed the cholinergic anti-inflammatory pathway. To explore this, we determined whether electrical neurostimulation of the cholinergic anti-inflammatory pathway reduced disease severity in the collagen-induced arthritis model. Rats implanted with vagus nerve cuff electrodes had collagen-induced arthritis induced and were followed for 15 days. Animals underwent active or sham electrical stimulation once daily from day 9 through the conclusion of the study. Joint swelling, histology, and levels of cytokines and bone metabolism mediators were assessed. Compared with sham treatment, active neurostimulation of the cholinergic anti-inflammatory pathway resulted in a 52% reduction in ankle diameter (p = 0.02), a 57% reduction in ankle diameter (area under curve; p = 0.02) and 46% reduction overall histological arthritis score (p = 0.01) with significant improvements in inflammation, pannus formation, cartilage destruction, and bone erosion (p = 0.02), accompanied by numerical reductions in systemic cytokine levels, not reaching statistical significance. Bone erosion improvement was associated with a decrease in serum levels of receptor activator of NF-κB ligand (RANKL) from 132±13 to 6±2 pg/mL (mean±SEM, p = 0.01). The severity of collagen-induced arthritis is reduced by neurostimulation of the cholinergic anti-inflammatory pathway delivered using an implanted electrical vagus nerve stimulation cuff electrode, and supports the rationale for testing this approach in human inflammatory disorders.
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影响因子：
6.2
作者：
Stolina, M;Adamu, S;Kostenuik, PJ
通讯作者：
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影响因子：
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期刊：
The Journal of experimental medicine
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DOI：
10.1126/science.1209985
发表时间：
2011-10-07
期刊：
Science (New York, N.Y.)
影响因子：
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DOI：
10.1152/ajpgi.00098.2007
发表时间：
2007-09-01
影响因子：
4.5
作者：
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