Cited by 315Vagus Nerve Stimulation ResearchHeart Rate Variability and Autonomic ControlTrauma, Hemostasis, Coagulopathy, Resuscitation

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Efferent Vagal Fibre Stimulation Blunts Nuclear Factor-κB Activation and Protects Against Hypovolemic Hemorrhagic Shock

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Guarini, Salvatore, Altavilla, Domenica, Cainazzo, Maria-Michela, Giuliani, Daniela, Bigiani, Albertino, Marini, Herbert, Squadrito, Giovanni, Minutoli, Letteria, Bertolini, Alfio, Marini, Rolando, Adamo, Elena B., Venuti, Francesco S., Squadrito, Francesco·2003·Circulation

DOI 10.1161/01.cir.0000050627.90734.ed

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Abstract

Background— We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-κB activation and the inflammatory cascade in hemorrhagic (Hem) shock. Methods and Results— Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg. Application of constant voltage pulses to the caudal vagus ends (STIM; 5 V, 2 ms, 1 Hz for 12 minutes, 5 minutes after mean arterial pressure stabilization) increased survival time (VGX+Hem+Sham STIM=38±3 minutes; VGX+Hem+STIM >180 minutes), reverted the marked hypotension (VGX+Hem+Sham STIM=33±3 mm Hg; VGX+Hem+STIM=66±5 mm Hg), inhibited IκBα liver loss, and blunted the augmented NF-κB activity, decreased hepatic tumor necrosis factor (TNF)-α mRNA (VGX+Hem+Sham STIM=1.42±0.5 amount of TNF-α m-RNA; VGX+Hem+STIM=0.51±0.2 amount of TNF-α mRNA), and reduced plasma TNF-α (VGX+Hem+Sham STIM=190±24 pg/mL; VGX+Hem+STIM=87±15 pg/mL). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation. Conclusions— Our results show a parasympathetic inhibition of NF-κB by which the brain opposes NF-κB activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.

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Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., Wang, H., Abumrad, N., Eaton, J. W., & Tracey, K. J. (2000) · Nature · doi:10.1038/35013070 · Cited by 4,211
Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF‐kappa B transcription factor and HIV‐1.
Schreck, R., RIEBER, P., & Baeuerle, P. A. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07761.x · Cited by 3,793
NF-κB: Ten Years After
Baeuerle, P. A., & Baltimore, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81318-5 · Cited by 3,002
Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
Scheinman, R. I., Cogswell, P. C., Lofquist, A. K., & Baldwin, A. S. (1995) · Science · doi:10.1126/science.270.5234.283 · Cited by 1,676
Immunoregulatory Feedback Between Interleukin-1 and Glucocorticoid Hormones
Besedovsky, H., del Rey, A., Sorkin, E., & Dinarello, C. A. (1986) · Science · doi:10.1126/science.3014662 · Cited by 1,519
Signal transduction through NF-κB
May, M. J., & Ghosh, S. (1998) · Immunology Today · doi:10.1016/s0167-5699(97)01197-3 · Cited by 1,098
Pharmacological stimulation of the cholinergic antiinflammatory pathway
Bernik, T. R., Friedman, S. G., Ochani, M., DiRaimo, R., Ulloa, L., Yang, H., Sudan, S., Czura, C. J., Ivanova, S. M., & Tracey, K. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20011714 · Cited by 529
Essential Role of Induced Nitric Oxide in the Initiation of the Inflammatory Response after Hemorrhagic Shock
Hierholzer, C., Harbrecht, B. G., Menezes, J. M., Kane, J., MacMicking, J. D., Nathan, C., Peitzman, A. B., Billiar, T. R., & Tweardy, D. J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.6.917 · Cited by 471
Neural-immune interactions in health and disease.
Sternberg, E. M. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119807 · Cited by 363
Anti-inflammatory actions of the neuroimmunomodulator α-MSH
Lipton, J. M., & Catania, A. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)01009-8 · Cited by 356

Show all 24 references

Research works printed but not linked: 6

1998, Immunol Today, 19, 81
1997, J Clin Invest, 18, 529
2001, Free Radic Biol Med, 10, 1055
2001, Cardiovasc Res, 52, 43
2000, J Pharmacol Exp Ther, 292, 1053
1992, Circ Shock, 37, 236

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Background
Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic
LIU, H. J., Li, X., Yu, J., & Chen, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1789297 · Cited by 3
“For instance, vagal electrical stimulation or nicotine agonism of a 7nAChR inhibits NF-k B transcriptional activity in human macrophages (124, 125), suppressing TNF a secretion (126).”
The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis
Hu, J., Liu, Y., Liu, S., Zhang, T., Chen, G., Zhao, J., & Ma, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.839290 · Cited by 3
“This so-called cholinergic anti-inflammatory pathway (CAP) is initiated in brain stem nuclei and exerts its effects via the vagus nerve by releasing acetylcholine (ACh) (9).”
Vagal-mAChR4 signaling promotes Friend virus complex (FV)-induced acute erythroleukemia
Song, S., Lin, Z., Zhao, C., Wen, J., Chen, J., Xie, S., Qi, H., Wang, J., & Su, X. (2023) · Virologica Sinica · doi:10.1016/j.virs.2023.05.005 · Cited by 3
Vagus Nerve Stimulation and Regulation of Inflammation
Olofsson, P. S. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-805353-9.00125-x · Cited by 4
Animal Models for the Study of Neonatal Disease
Praud, J., Miura, Y., & Frasch, M. G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809468-6.00031-0 · Cited by 5
Pro-resolving Mediators
Gonçalves, W. A., Melão, A. C. R., Teixeira, M. M., Rezende, B. M., & Pinho, V. (2018) · Springer eBooks · doi:10.1007/978-3-319-77658-3_6 · Cited by 3
Mechanical vagus nerve stimulation—A new adjunct in sepsis prophylaxis and treatment?*
Bauhofer, A., & Torossian, A. (2007) · Critical Care Medicine · doi:10.1097/00003246-200712000-00035 · Cited by 3
Pathophysiology and treatment of the systemic inflammatory response syndrome from the perspective of evolutionary medicine
Fujita, T. (2010) · Surgery · doi:10.1016/j.surg.2009.11.006 · Cited by 3
Research Progress in Ultrasonic Regulation of Cholinergic Anti-inflammatory Pathwa
Zhou, W., Song, M. Y., Wang, M. R., Jin, M. Q., Xie, P. M., & Zhang, P. L. (2022) · Advanced ultrasound in diagnosis and therapy · doi:10.37015/audt.2022.200034 · Cited by 2
Comparison of heart rate variability, hemodynamic, metabolic and inflammatory parameters in various phases of decompansatory hemorrhagic shock of normal and vagotomized conscious male rats
Khodadadi, F., Punait, S., Ketabchi, F., Khodabandeh, Z., Bahaoddini, A., & Lewis, G. F. (2024) · BMC Cardiovascular Disorders · doi:10.1186/s12872-024-04342-8 · Cited by 2
α7 nicotinic acetylcholine receptor agonist attenuates lipopolysaccharide-induced acute kidney injury in mice by reducing CCL2 expression in macrophages
Matsuo, S., Uni, R., Wu, C.-H., Nakamura, Y., Umene, R., Surattichaiyakul, B., Nangaku, M., Inagi, R., Nishino, T., & Inoue, T. (2025) · Scientific Reports · doi:10.1038/s41598-025-23583-x · Cited by 2
Neural regulation of gut inflammation via autonomic nerves: therapeutic implications for inflammatory bowel disease
Hasegawa, M., Kawaguchi, T., Kiyohara, H., Teratani, T., Nakamoto, N., Mikami, Y., & Kanai, T. (2025) · Immunological Medicine · doi:10.1080/25785826.2025.2604347 · Cited by 2
The effect of subdiaphragmatic vagotomy on heart rate variability and lung inflammation in rats with severe hemorrhagic shock
Khodadadi, F., Ketabchi, F., Khodabandeh, Z., Tavassoli, A., Lewis, G. F., & Bahaoddini, A. (2022) · BMC Cardiovascular Disorders · doi:10.1186/s12872-022-02594-w · Cited by 2
Autoantibodies to the α7 Subunit of the Neuronal Acetylcholine Receptor in Craniocerebral Trauma in Children
Sorokina, E. G., Volpina, O. M., Семенова, Ж. Б., et al. (2012) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-012-9627-6 · Cited by 2
“The use of selective inhibitors of the α7-subunit has demonstrated their efficacy in experimental models of sepsis [20], hemorrhagic shock [14], and states such as pancreatitis [23].”
[The effect of cholinergic stimulation on autonomic balance and immune response in patients with chronic heart failure].
Biel, B., Jankowska, E. A., Banasiak, W., & Ponikowski, P. P. (2007) · PubMed · Cited by 2
Does the vagus nerve mediate the effects of polyunsaturated fatty acid treatment on behavioral, neuroendocrine and cytokine changes elicited by exogenous interleukin-1β challenge?
Mravec, B. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.011 · Cited by 2
“Research provided the evidence of the profound effects of activated anti-inflammatory efferent pathways of the vagus nerve on various physiological and pathological conditions (Borovikova et al., 2000; Guarini et al., 2003; van Westerloo et al., 2006).”
Background
Correction to: GTS-21, an α7nAChR agonist, increases pulmonary bacterial clearance in mice by restoring hyperoxia-compromised macrophage function
Sitapara, R. A., Gauthier, A. G., Patel, V., et al. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00357-5 · Cited by 2
Progress on Direct Regulation of Systemic Immunity by the Central Nervous System
Tan, X., Zhang, J., Chen, W.-M., Chen, T., Cui, G., Liu, Z., & Hu, R. (2025) · World Neurosurgery · doi:10.1016/j.wneu.2025.123814 · Cited by 2
Vagotomy and immune response
de la Cruz-Aguilera, D. L., Calleja, J. A., Rangel, E., Espinoza, G. M., & Aguirre‐Cruz, L. (2011) · Archivos de Neurociencias · Cited by 1
Aortic Depressor Nerve Stimulation Markedly Improves the Survival Rate after Acute Myocardial Infarction in Rats
Ariumi, H., & Yoshiyama, Y. (2011) · Journal of oral tissue engineering · doi:10.11223/jarde.9.17 · Cited by 1
Characteristic Changes in Heart Rate Variability Indices during Hemorrhagic Shock, and Effect of Liposome-Encapsulated Hemoglobin in Rats
Nogami, Y., Takase, B., Kinoshita, M., et al. (2010) · Journal of Arrhythmia · doi:10.1016/s1880-4276(10)80006-7 · Cited by 1
Efficacy of auricular acupuncture on inflammatory markers and insulin resistance in type 2 diabetes model of rats: In light of cholinergic anti-inflammatory pathway
Mei, Z., Yong-bao, Z., Xiao-jie, L., & Ming-zhi, W. (2011) · International Conference on Human Health and Biomedical Engineering · doi:10.1109/hhbe.2011.6029053 · Cited by 1
“Activating CAP by acupuncture or electric stimulation has also been reported to not only decrease the levels of TNF- in liver, kidney and jejunum tissues after cecal ligation and puncture (GLP) [41], but also protect efficacy on rats with acute hypovolemic hemorrhagic shock[42]and prevent postoperative intestinal infl…”
Background
Progenitor Cell Therapy for the Treatment of Traumatic Brain Injury
Olsen, A. B., Hetz, R. A., Bedi, S. S., & Cox, C. S. (2013) · Wiley eBooks · doi:10.1002/9781118497883.ch11 · Cited by 1
Chapter 8: General Discussion
Xie, Z. (2016) · Peter Lang eBooks · doi:10.3726/978-3-0351-0938-2/11 · Cited by 1
The effects of a maternal high fat diet on hepatic innervation in the nonhuman primate
Grant, W. F. (2011) · doi:10.6083/m4kw5d1c
Udział układu histaminergicznego w działaniu resuscytacyjnym wywołanym pobudzeniem ośrodkowych receptorów melanokortynowych typu 4 u szczurów we wstrząsie krwotocznym
Jochem, J., Walas, K., & Nowak, D. (2014) · Annales Academiae Medicae Silesiensis
Neural Regulation of Cytokines
Huston, J. M., & Tracey, K. J. (2008) · Wiley eBooks · doi:10.1002/9783527626151.ch13
Cholinergic nervous system as therapeutic approach for the treatment of arthritis
van Maanen, M. A. (2009) · Data Archiving and Networked Services (DANS)
Interação da atividade autonômica e resposta imunomoduladora na fase aguda do infarto do miocárdio experimental
Rocha, J. A. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2013.tde-22012014-122449
The alloantigen-independent factors brain death and cold ischemia: prospects for a better graft survival through different donor management concepts
Höger, S. (2009) · University of Groningen research database (University of Groningen / Centre for Information Technology)
The Cholinergic Anti-inflammatory Pathway: Connecting the Mind and Body
Czura, C. J., Friedman, S., & Tracey, K. J. (2006) · Springer eBooks · doi:10.1007/3-540-30328-6_18
“Vagus nerve stimulation is also effective in animal models of inflammation that are independent of endotoxin, including transient aortic occlusion with reperfusion injury [5], myocardial ischemia/reperfusion injury [17], carrageenan-induced hindlimb edema [18], and hypovolemic shock [ 19 , 20].”
Background
Therapeutic Potentials of Enteric Nerve Activation with Vagus Nerve Stimulation.
Fujita, T. (2016) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2015.10.002
Role of the cholinergic anti-inflammatory pathway in endotoxemia-induced multi-organ damage in the rat
Kolgazi, M., Ozgur, F., Beyazoglu, O., Kocagoz, A., Celik, M., Elmas, M. A., Yüksel, M., Ercan, F., & Ali̇can, İ. (2015) · Clinical and Experimental Health Sciences · doi:10.5455/musbed.20150306053623
Efeito da hipofunção colinérgica na mecânica e na histopatologia pulmonar em modelo experimental de inflamação pulmonar induzida por instilação de poluente em camundongos
Paulo, S. (2014)
Aus dem Institut für Physiologie der Medizinischen Fakultät Charité - Universitätsmedizin Berlin
Enigk, F. (2015)
Review Article Cholinergic Modulation of Inflammation
Pavlov, V. A. (2008)
Stress Sounds the Alarmin: High Mobility Group Box 1 as a Stress-Induced Neuroinflammatory Priming Signal
Weber, M. D. (2015) · CU Scholar (University of Colorado Boulder)

Authors: Guarini, S., Altavilla, D., Cainazzo, M.-M., Giuliani, D., Bigiani, A., Marini, H., Squadrito, G., Minutoli, L., Bertolini, A., Marini, R., Adamo, E. B., Venuti, F. S., & Squadrito, F.
Affiliations: University of Modena and Reggio Emilia (IT)
ORCID: Guarini, Salvatore
Altavilla, Domenica
Giuliani, Daniela
Bigiani, Albertino
Marini, Herbert
Squadrito, Giovanni
Minutoli, Letteria
Squadrito, Francesco
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2003-03-04
Volume: 107
Issue: 8
Pages: 1189-1194
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.0000050627.90734.ed
OpenAlex: W2098655301
Semantic Scholar: 919d8a5ae0075ccd6d7dd152a6fe9773763923b4
Cited by: 315
References: 24
Citations by year: 2026: 2 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 14 · 2021: 13 · 2020: 18 · 2019: 12 · 2018: 10 · 2017: 15 · 2016: 10 · 2015: 18 · 2014: 22 · 2013: 16 · 2012: 21
FWCI: 6.64
Type: journal article
Language: en
Update notices: expression_of_concern (2022-08-23)
Open access: green
hdl.handle.net
Licence: cc-by
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
Funders: Consiglio Nazionale delle Ricerche
Università degli Studi di Messina
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
Keywords: vagus nerve stimulation, NF-κB activation, inflammation, TNF-α, parasympathetic nervous system, vagotomy, nicotinic acetylcholine receptors, liver inflammation
MeSH terms: NF-KappaB Inhibitor alpha, Animals, Blood Pressure, Efferent Pathways, Electric Stimulation, Inflammation, Liver, Male, Nerve Fibers, RNA, Messenger, Shock, Hemorrhagic, Tumor Necrosis Factor-alpha, Vagus Nerve, Survival Analysis, NF-kappa B, Rats, Wistar, I-kappa B Proteins, Hypovolemia, Rats

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Efferent Vagal Fibre Stimulation Blunts Nuclear Factor-κB Activation and Protects Against Hypovolemic Hemorrhagic Shock

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