Voltammetry in the spleen assesses real-time anti-inflammatory norepinephrine release elicited by autonomic neurostimulation

Author:

Mughrabi Ibrahim T.ORCID,Gerber MichaelORCID,Jayaprakash NaveenORCID,Palandira Santhoshi P.,Al-Abed Yousef,Datta-Chaudhuri TimirORCID,Smith Corey,Pavlov Valentin A.,Zanos Stavros

Abstract

AbstractBackgroundThe noradrenergic innervation of the spleen is implicated in the autonomic control of inflammation and has been the target of neurostimulation therapies for inflammatory diseases. However, there is no real-time marker of its successful activation, which hinders the optimization of anti- inflammatory neurostimulation therapies and mechanistic studies in anti-inflammatory neural circuits.MethodsIn mice, we performed fast-scan cyclic voltammetry (FSCV) in the spleen during intravascular injections of norepinephrine (NE), or during stimulation of the vagus, splanchnic, or splenic nerves. We defined the stimulus-elicited charge generated at the oxidation potential for NE (∼0.8 V) as the “NE voltammetry signal” and quantified the dependence of the signal on NE or nerve stimulation dose. We correlated the NE voltammetry signal in response to splenic nerve stimulation (SpNS) with the latter’s anti-inflammatory effect in a model of lipopolysaccharide- (LPS) induced endotoxemia, quantified as suppression of TNF release.ResultsWe found that the NE voltammetry signal is proportional to injected amount and estimated peak NE concentration, with 0.3 μM detection threshold. In response to SpNS, the signal increases within seconds, returns to baseline minutes later and is blocked by interventions that deplete NE or inhibit NE release. The signal is elicited by efferent, but not afferent, electrical or optogenetic vagus nerve stimulation, and by splanchnic nerve stimulation. The magnitude of the signal during SpNS is inversely correlated with subsequent TNF suppression in endotoxemia and explains 40% of the variance in TNF measurements.ConclusionFSCV in the spleen provides a marker for real-time monitoring of anti-inflammatory activation of the splenic innervation during autonomic stimulation.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3