{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:33:39Z","timestamp":1783722819013,"version":"3.55.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T00:00:00Z","timestamp":1606867200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Labex Signalife","award":["#ANR-11-LABX-0028-01"],"award-info":[{"award-number":["#ANR-11-LABX-0028-01"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The carotid bodies and baroreceptors are sensors capable of detecting various physiological parameters that signal to the brain via the afferent carotid sinus nerve for physiological adjustment by efferent pathways. Because receptors for inflammatory mediators are expressed by these sensors, we and others have hypothesised they could detect changes in pro-inflammatory cytokine blood levels and eventually trigger an anti-inflammatory reflex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test this hypothesis, we surgically isolated the carotid sinus nerve and implanted an electrode, which could deliver an electrical stimulation package prior and following a lipopolysaccharide injection. Subsequently, 90 min later, blood was extracted, and cytokine levels were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we found that carotid sinus nerve electrical stimulation inhibited lipopolysaccharide-induced tumour necrosis factor production in both anaesthetised and non-anaesthetised conscious mice. The anti-inflammatory effect of carotid sinus nerve electrical stimulation was so potent that it protected conscious mice from endotoxaemic shock-induced death. In contrast to the mechanisms underlying the well-described vagal anti-inflammatory reflex, this phenomenon does not depend on signalling through the autonomic nervous system. Rather, the inhibition of lipopolysaccharide-induced tumour necrosis factor production by carotid sinus nerve electrical stimulation is abolished by surgical removal of the adrenal glands, by treatment with the glucocorticoid receptor antagonist mifepristone or by genetic inactivation of the glucocorticoid gene in myeloid cells. Further, carotid sinus nerve electrical stimulation increases the spontaneous discharge activity of the hypothalamic paraventricular nucleus leading to enhanced production of corticosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Carotid sinus nerve electrostimulation attenuates inflammation and protects against lipopolysaccharide-induced endotoxaemic shock via increased corticosterone acting on the glucocorticoid receptor of myeloid immune cells. These results provide a rationale for the use of carotid sinus nerve electrostimulation as a therapeutic approach for immune-mediated inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-020-02016-8","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T07:02:57Z","timestamp":1606892577000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Electrostimulation of the carotid sinus nerve in mice attenuates inflammation via glucocorticoid receptor on myeloid immune cells"],"prefix":"10.1186","volume":"17","author":[{"given":"Aidan","family":"Falvey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Duprat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Hugues-Ascery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia V.","family":"Conde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Glaichenhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8997-0470","authenticated-orcid":false,"given":"Philippe","family":"Blancou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"2016_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1002\/path.2287","volume":"214","author":"JR Bradley","year":"2008","unstructured":"Bradley JR. TNF-mediated inflammatory disease. J Pathol. 2008;214:149\u201360.","journal-title":"J Pathol."},{"key":"2016_CR2","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/BF03402177","volume":"9","author":"VA Pavlov","year":"2003","unstructured":"Pavlov VA, et al. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003;9:125\u201334.","journal-title":"Mol Med."},{"key":"2016_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/physrev.1999.79.1.1","volume":"79","author":"AV Turnbull","year":"1999","unstructured":"Turnbull AV, Rivier CL. Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev. 1999;79:1\u201371.","journal-title":"Physiol Rev."},{"key":"2016_CR4","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1084\/jem.20120571","volume":"209","author":"U Andersson","year":"2012","unstructured":"Andersson U, Tracey KJ. Neural reflexes in inflammation and immunity. J Exp Med. 2012;209:1057\u201368.","journal-title":"J Exp Med."},{"key":"2016_CR5","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1111\/nmo.12792","volume":"28","author":"B Bonaz","year":"2016","unstructured":"Bonaz B, et al. Chronic vagus nerve stimulation in Crohn\u2019s disease: a 6-month follow-up pilot study. Neurogastroenterol Motil. 2016;28:948\u201353.","journal-title":"Neurogastroenterol Motil."},{"issue":"29","key":"2016_CR6","doi-asserted-by":"publisher","first-page":"8284","DOI":"10.1073\/pnas.1605635113","volume":"113","author":"FA Koopman","year":"2016","unstructured":"Koopman FA, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci. 2016;113;29:8284\u20139.","journal-title":"Proc Natl Acad Sci."},{"key":"2016_CR7","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nrd4351","volume":"13","author":"K Birmingham","year":"2014","unstructured":"Birmingham K, et al. Bioelectronic medicines: a research roadmap. Nat Rev Drug Discov. 2014;13:399\u2013400.","journal-title":"Nat Rev Drug Discov."},{"key":"2016_CR8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/cphy.c100069","volume":"2","author":"P Kumar","year":"2012","unstructured":"Kumar P, Prabhakar NR. Peripheral chemoreceptors: function and plasticity of the carotid body. Compr Physiol. 2012;2:141\u2013219.","journal-title":"Compr Physiol."},{"key":"2016_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2014.00418","volume":"5","author":"SV Conde","year":"2014","unstructured":"Conde SV, et al. Carotid body, insulin and metabolic diseases: unravelling the links. Front Physiol. 2014;5:1\u201314.","journal-title":"Front Physiol."},{"key":"2016_CR10","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1002\/jnr.22107","volume":"87","author":"J Fan","year":"2009","unstructured":"Fan J, et al. Interleukin-6 increases intracellular Ca2+ concentration and induces catecholamine secretion in rat carotid body glomus cells. J Neurosci Res. 2009;87:2757\u201362.","journal-title":"J Neurosci Res."},{"issue":"7","key":"2016_CR11","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1113\/expphysiol.2008.041152","volume":"93","author":"R Fernandez","year":"2008","unstructured":"Fernandez R, et al. Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-\u03b1. Exp Physiol. 2008;93(7):892\u2013907.","journal-title":"Exp Physiol."},{"key":"2016_CR12","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1111\/j.1460-9568.2007.05586.x","volume":"25","author":"HF Shu","year":"2007","unstructured":"Shu HF, et al. IL-1\u03b2 inhibits IK and increases [Ca2+] in the carotid body glomus cells and increases carotid sinus nerve firings in the rat. Eur J Neurosci. 2007;25:3638\u201347.","journal-title":"Eur J Neurosci."},{"key":"2016_CR13","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/CCM.0b013e31827c0b05","volume":"41","author":"GL Ackland","year":"2013","unstructured":"Ackland GL, et al. Peripheral neural detection of danger-associated and pathogen-associated molecular patterns. Crit Care Med. 2013;41:85\u201392.","journal-title":"Crit Care Med."},{"key":"2016_CR14","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.resp.2010.12.014","volume":"175","author":"R Fern\u00e1ndez","year":"2011","unstructured":"Fern\u00e1ndez R, et al. Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome. Respir Physiol Neurobiol. 2011;175:336\u201348.","journal-title":"Respir Physiol Neurobiol."},{"key":"2016_CR15","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s00418-008-0437-4","volume":"130","author":"SL George","year":"2008","unstructured":"George SL, Emily LT, Fung M. Chronic hypoxia upregulates the expression and function of proinflammatory cytokines in the rat carotid body. Histochem Cell Biol. 2008;130:549\u201359.","journal-title":"Histochem Cell Biol."},{"key":"2016_CR16","first-page":"10","volume":"12","author":"J Wang","year":"2017","unstructured":"Wang J, et al. Distinct and common expression of receptors for inflammatory mediators in vagal nodose versus jugular capsaicin-sensitive\/TRPV1-positive neurons detected by low input RNA sequencing. Plos One. 2017;12:10.","journal-title":"Plos One."},{"key":"2016_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-06703-0","volume":"7","author":"FM Santos-Almeida","year":"2017","unstructured":"Santos-Almeida FM, et al. Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation. Sci Rep. 2017;7:1\u20138.","journal-title":"Sci Rep."},{"key":"2016_CR18","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.brainres.2018.01.003","volume":"1682","author":"F Brognara","year":"2018","unstructured":"Brognara F, et al. Baroreflex stimulation attenuates central but not peripheral inflammation in conscious endotoxemic rats. Brain Res. 2018;1682:54\u201360.","journal-title":"Brain Res."},{"key":"2016_CR19","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jneuroim.2014.12.002","volume":"278","author":"G Nardocci","year":"2015","unstructured":"Nardocci G, et al. Sepsis progression to multiple organ dysfunction in carotid chemo\/baro-denervated rats treated with lipopolysaccharide. J Neuroimmunol. 2015;278:44\u201352.","journal-title":"J Neuroimmunol."},{"key":"2016_CR20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1128\/CVI.13.2.281-288.2006","volume":"13","author":"JM Fuentes","year":"2006","unstructured":"Fuentes JM, et al. General anesthesia delays the inflammatory response and increases survival for mice with endotoxic shock. Clin Vaccine Immunol. 2006;13:281\u20138.","journal-title":"Clin Vaccine Immunol."},{"key":"2016_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fphys.2014.00489","volume":"5","author":"R Fernandez","year":"2014","unstructured":"Fernandez R, et al. Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy. Front Physiol. 2014;5:1\u20139.","journal-title":"Front Physiol."},{"key":"2016_CR22","doi-asserted-by":"publisher","first-page":"3807","DOI":"10.1113\/jphysiol.2012.231084","volume":"590","author":"S Mkrtchian","year":"2012","unstructured":"Mkrtchian S, et al. The human carotid body transcriptome with focus on oxygen sensing and inflammation - a comparative analysis. J Physiol. 2012;590:3807\u201319.","journal-title":"J Physiol."},{"key":"2016_CR23","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1177\/002215540205001213","volume":"50","author":"X Wang","year":"2002","unstructured":"Wang X, et al. Strong expression of interleukin-1 receptor type I in the rat carotid body. J Histochem Cytochem. 2002;50:1677\u201384.","journal-title":"J Histochem Cytochem."},{"key":"2016_CR24","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ar.a.20310","volume":"288","author":"X Wang","year":"2006","unstructured":"Wang X, et al. Morphological evidence for existence of IL-6 receptor alpha in the glomus cells of rat carotid body. Anat Rec A Discov Mol Cell Evol Biol. 2006;288:292\u20136.","journal-title":"Anat Rec A Discov Mol Cell Evol Biol."},{"key":"2016_CR25","doi-asserted-by":"publisher","first-page":"37","DOI":"10.15424\/bioelectronmed.2015.00006","volume":"2","author":"PS Olofsson","year":"2015","unstructured":"Olofsson PS, et al. Single-pulse and unidirectional electrical activation of the cervical vagus nerve reduces tumor necrosis factor in endotoxemia. Bioelectron Med. 2015;2:37\u201342.","journal-title":"Bioelectron Med."},{"key":"2016_CR26","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3181\/00379727-172-41578","volume":"406","author":"H Raff","year":"1983","unstructured":"Raff H, Shinsako J, Dallman MF. Surgery potentiates adrenocortical responses to hypoxia in dogs. Proc Soc Exp Med Biol. 1983;406:400\u20136.","journal-title":"Proc Soc Exp Med Biol."},{"key":"2016_CR27","doi-asserted-by":"publisher","first-page":"7979","DOI":"10.1523\/JNEUROSCI.15-12-07979.1995","volume":"15","author":"DW Smith","year":"1995","unstructured":"Smith DW, Buller KM, Day TA. Role of ventrolateral medulla catecholamine cells in hypothalamic neuroendocrine cell responses to systemic hypoxia. J Neurosci. 1995;15:7979\u201388.","journal-title":"J Neurosci."},{"key":"2016_CR28","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/S0006-8993(99)02304-5","volume":"857","author":"P Berquin","year":"2000","unstructured":"Berquin P, et al. Brainstem and hypthalamic areas involved in respiratory chemoreflexes: a Fos study in adult rats. Brain Res. 2000;857:30\u201340.","journal-title":"Brain Res."},{"key":"2016_CR29","first-page":"2563","volume":"2014","author":"MD Turner","year":"1843","unstructured":"Turner MD, et al. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. BBA Mol Cell Res. 1843;2014:2563\u201382.","journal-title":"BBA Mol Cell Res."}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-02016-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12974-020-02016-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-02016-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T22:43:41Z","timestamp":1669934621000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-02016-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2016"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-02016-8","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"26 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All studies conducted within this manuscript have obtained ethical approval and comply with the regulations set forth by both local (Alpes-Maritimes) and national (France) commissions for the treatment of experimental animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors of this manuscript consent to the publication of these results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors and this manuscript have no conflict of interest nor competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"368"}}