Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model.

Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model.
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DOI:
10.1088/1741-2552/aaa039
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发表时间:
2018-06
影响因子:
4
通讯作者:
Irazoqui PP
Irazoqui PP
中科院分区:
工程技术2区
文献类型:
--
作者:
Somann JP;Albors GO;Neihouser KV;Lu KH;Liu Z;Ward MP;Durkes A;Robinson JP;Powley TL;Irazoqui PP

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大量关于迷走神经刺激 (VNS) 的研究已发表,表明它是治疗慢性炎症和其他相关疾病和病症的潜在方法。近年来的研究表明,电刺激迷走神经传出纤维可以人为调节细胞因子水平并减少系统炎症。大多数 VNS 治疗炎症的研究都是针对啮齿类动物的急性研究。我们的研究通过使用神经袖带电极长时间刺激和记录颈部迷走神经,在自由活动的动物上测试了 VNS。我们使用电刺激、逆行追踪(使用 Fluorogold)和尸检后神经组织组织学分析、流式细胞术测量血浆细胞因子水平以及胃排空 MRI 扫描的方法。这种新颖的方法组合允许检查以前未探索过的 VNS 的生理方面。通过对 53 名大鼠受试者的研究,我们发现长期套住左颈迷走神经会抑制 44 只动物中 43 只的传出氟金转运(其中 36 只表现出完全抑制)。测量的细胞因子水平和胃排空率同时显示出长期戴袖套的大鼠和用类似急性方法测试的大鼠之间存在名义差异。与此同时,对被套住的神经进行的电生理学和组织学测试结果显示,它们在其他方面都是健康的,这与之前的文献一致。我们假设,由于大鼠迷走神经长期套带的这些不可预见和未探索的生理后果,VNS 的炎症调节和其他迷走神经作用在长期研究中可能变得不可靠。鉴于我们的研究结果,我们认为重新检查先前文献中使用的方法以验证大鼠模型对慢性 VNS 研究的有效性将有利于 VNS 界。
Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.
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