Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway
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OBJECTIVE: Several melanocortin peptides have a prompt and sustained resuscitating effect in conditions of hemorrhagic shock. The transcription nuclear factor kappaB (NF-kappaB) triggers a potentially lethal systemic inflammatory response, with marked production of tumor necrosis factor-alpha (TNF-alpha), in hemorrhagic shock. Here we investigated whether the hemorrhagic shock reversal produced by the melanocortin ACTH-(1-24) (adrenocorticotropin) depends on the activation of the recently recognized, vagus nerve-mediated, brain "cholinergic anti-inflammatory pathway". METHODS AND RESULTS: Anesthetized rats were stepwise bled until mean arterial pressure (MAP) stabilized at 20-25 mm Hg. The severe hypovolemia was incompatible with survival, and all saline-treated animals died within 30 min. In rats intravenously (i.v.) treated with ACTH-(1-24), neural efferent activity along vagus nerve (monitored by means of a standard system for extracellular recordings) was markedly increased, and the restoration of cardiovascular and respiratory functions was associated with blunted NF-kappaB activity and with decreased TNF-alpha mRNA liver content and TNF-alpha plasma levels. Bilateral cervical vagotomy, pretreatment with the melanocortin MC(4) receptor antagonist HS014, atropine sulfate or chlorisondamine, but not with atropine methylbromide, prevented the life-saving effect of ACTH-(1-24) and the associated effects on NF-kappaB activity and TNF-alpha levels. HS014 and atropine sulfate prevented, too, the ACTH-(1-24)-induced increase in neural efferent vagal activity, and accelerated the evolution of shock in saline-treated rats. CONCLUSIONS: The present data show, for the first time, that the melanocortin ACTH-(1-24) suppresses the NF-kappaB-dependent systemic inflammatory response triggered by hemorrhage, and reverses shock condition, by brain activation (in real-time) of the "cholinergic anti-inflammatory pathway", this pathway seeming to be melanocortin-dependent.
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Administration of ACTH 1-24 significantly increases vagus nerve activity in rats.
“Another approach to stimulating efferent activity in the cholinergic antiinflammatory pathway in this model is by administration of adrenocorticotropic hormone (ACTH 1-24 ), which significantly increased vagus nerve activity in rats.”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [40]
ACTH 1-24 activates proximal neural networks that increase efferent activity in the cholinergic antiinflammatory pathway to suppress cytokine-mediated damage.
“Bilateral vagotomy ablated the protective effects of ACTH 1-24 in hemorrhagic shock, providing evidence that ACTH 1-24 activates proximal neural networks that increase efferent activity in the cholinergic antiinflammatory pathway to suppress cytokine-mediated damage (40).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [40]
Hemorrhagic shock reversal is mediated via CNS POMC-MC4Rs.
“In addition, previous studies also showed that hemorrhagic shock reversal is mediated via CNS POMC-MC4Rs and may involve activation of efferent vagal cholinergic pathways [74].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [74]
Hemorrhagic shock reversal may involve activation of efferent vagal cholinergic pathways.
“In addition, previous studies also showed that hemorrhagic shock reversal is mediated via CNS POMC-MC4Rs and may involve activation of efferent vagal cholinergic pathways [74].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [74]
Microinjections of α-MSH in the nucleus ambiguus exert excitatory effects on parasympathetic preganglionic neurons via activation of MC4R, resulting in increased vagal input to the heart and bradycardia responses.
“For instance, microinjections of α-MSH in the nucleus ambiguus (nAMB) exerted excitatory effects on parasympathetic preganglionic neurons via activation of MC4R, resulting in increased vagal input to the heart and bradycardia responses [74–76].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [74]
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Cites
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 · see citing works
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · see citing works
Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation
Wang, H., Yu, M., Ochani, M., Amella, C. A., Tanovic, M., Susarla, S., Li, J. H., Wang, H., Yang, H., Ulloa, L., et al. (2003) · Nature · doi:10.1038/nature01339 · Cited by 3,228 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Neuropeptides derived from pro-opiocortin: behavioral, physiological, and neurochemical effects.
de Wied, D., & JOLLES, J. (1982) · Physiological Reviews · doi:10.1152/physrev.1982.62.3.976 · Cited by 493 · see citing works
Targeting melanocortin receptors as a novel strategy to control inflammation
Catania, A., Gatti, S., Colombo, G., & Lipton, J. M. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.1.1 · Cited by 438 · see citing works
Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation
Borovikova, L. V., Ivanova, S., Nardi, D., Zhang, M., Yang, H., Ombrellino, M., & Tracey, K. J. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00233-2 · Cited by 322 · see citing works
New aspects on the melanocortins and their receptors
Wikberg, J. E. S., Muceniece, R., Mandrika, I., Prūsis, P., Lindblom, J., Post, C., & Skottner, A. (2000) · Pharmacological Research · doi:10.1006/phrs.2000.0725 · Cited by 318 · see citing works
Guarini, S., Altavilla, D., Cainazzo, M.-M., Giuliani, D., Bigiani, A., Marini, H., Squadrito, G., Minutoli, L., Bertolini, A., Marini, R., et al. (2003) · Circulation · doi:10.1161/01.cir.0000050627.90734.ed · Cited by 315 · see citing works
Self-citationTulzo, Y. L., Shenkar, R., Kaneko, D., Moine, P., Fantuzzi, G., Dinarello, C. A., & Abraham, E. H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119314 · Cited by 187 · see citing works
The effect of norepinephrine on endotoxin-mediated macrophage activation
Hu, X., Goldmuntz, E. A., & Brosnan, C. F. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90084-k · Cited by 119 · see citing works
The cell in shock: the origin of multiple organ failure
Schlag, G., Redl, H. R., & Hallström, S. (1991) · Resuscitation · doi:10.1016/0300-9572(91)90044-y · Cited by 118 · see citing works
Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions
Macaluso, A., McCoy, D., Ceriani, G., Watanabe, T., BILTZ, J., Catania, A. P., & Jm, L. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-04-02377.1994 · Cited by 97 · see citing works
Bertolini, A., Guarini, S., Rompianesi, E., & Ferrari, W. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90179-2 · Cited by 96 · see citing works
Self-citationα-Melanocyte-stimulating Hormone in Normal Human Physiology and Disease States
Catania, A. P., Airaghi, L., Colombo, G. I., & Lipton, J. M. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00296-4 · Cited by 74 · see citing works
Oxidative stress causes nuclear factor-κB activation in acute hypovolemic hemorrhagic shock
Altavilla, D., Saitta, A., Guarini, S., Galeano, M., Squadrito, G., Cucinotta, D., Santamaria, L. B., Mazzeo, A. T., Campo, G. M., Ferlito, M., et al. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00492-0 · Cited by 71 · see citing works
Self-citationMelanocortin peptides and their receptors: new targets for anti-inflammatory therapy
Getting, S. J. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(02)02103-x · Cited by 64 · see citing works
Protective effect of melanocortin peptides in rat myocardial ischemia
Bazzani, C., Guarini, S., Botticelli, A. R., Zaffe, D., Tomasi, A., Bini, A., Cainazzo, M. M., Ferrazza, G., Mioni, C., & Bertolini, A. (2001) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29636-1 · Cited by 59 · see citing works
Self-citationAdrenal-independent, anti-shock effect of ACTH-(1–24) in rats
Bertolini, A., Guarini, S., & Ferrari, W. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90424-3 · Cited by 58 · see citing works
Self-citationThe opioid/anti-opioid balance in shock: a new target for therapy in resuscitation
Bertolini, A. (1995) · Resuscitation · doi:10.1016/0300-9572(94)00863-b · Cited by 55 · see citing works
Guarini, S., Bazzani, C., Cainazzo, M. M., Mioni, C., Ferrazza, G., Vergoni, A. V., Schiöth, H. B., Wikberg, J. E. S., & Bertolini, A. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35205-x · Cited by 44 · see citing works
Self-citationSurvival rate after early treatment for acute type-A aortic dissection with ACTH-(1–24)
Noera, G., Lamarra, M., Guarini, S., & Bertolini, A. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05631-8 · Cited by 43 · see citing works
Self-citationReversal of haemorrhagic shock in rats by cholinomimetic drugs
Guarini, S., Tagliavini, S., Ferrari, W., & Bertolini, A. (1989) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1989.tb16885.x · Cited by 43 · see citing works
Self-citationShock, Sepsis, and Organ Failure
(1999) · Springer eBooks · doi:10.1007/978-3-642-58630-9 · Cited by 43 · see citing works
Resuscitating effect of melanocortin peptides after prolonged respiratory arrest
Guarini, S., Bazzani, C., & Bertolini, A. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701264 · Cited by 39 · see citing works
Self-citationAltavilla, D., Cainazzo, M. M., Squadrito, F., Guarini, S., Bertolini, A., & Bazzani, C. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702038 · Cited by 37 · see citing works
Self-citationGuarini, S., Bazzani, C., Ricigliano, G. M., Bini, A., Tomasi, A., & Bertolini, A. (1996) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1996.tb15673.x · Cited by 36 · see citing works
Self-citationSquadrito, F., Guarini, S., Altavilla, D., Squadrito, G., Campo, G. M., Arlotta, M., Quartarone, C., Saitta, A., Cucinotta, D., Bazzani, C., et al. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702848 · Cited by 34 · see citing works
Self-citationGuarini, S., Tagliavini, S., Bazzani, C., Ferrari, W., & Bertolini, A. (1990) · Critical Care Medicine · doi:10.1097/00003246-199008000-00014 · Cited by 32 · see citing works
Self-citationAdrenocorticotropin normalizes the blood levels of nitric oxide in hemorrhage-shocked rats
Guarini, S., Bini, A., Bazzani, C., Ricigliano, G. M., Cainazzo, M. M., Tomasi, A., & Alfio, B. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01210-7 · Cited by 31 · see citing works
Self-citationLudbrook, J., & Ventura, S. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00003-4 · Cited by 28 · see citing works
The life-saving effect of physostigmine in haemorrhagic shock
Savić, J., Varagić, V. M., Prokić, D., Vujnov, S., Prostran, M. S., Žunić, G. D., Stanimirovic, D. B., & Rastovac-Bogdanović, M. (1991) · Resuscitation · doi:10.1016/0300-9572(91)90078-d · Cited by 17 · see citing works
Alterations in Inflammatory Cytokine Production Following Hemorrhage and Resuscitation
Chaudry, I. H., Ertel, W., & Ayala, A. (1993) · Springer eBooks · doi:10.1007/978-3-642-77420-1_5 · Cited by 16 · see citing works
Onat, F., Aslan, N., Gören, Z., Özkutlu, U., & Oktay, Ş. (1994) · Brain Research · doi:10.1016/0006-8993(94)91298-x · Cited by 16 · see citing works
Nicotine reverses hemorrhagic shock in rats
Guarini, S., Tagliavini, S., Bazzani, C., Bertolini, A., & Ferrari, W. (1991) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf00179049 · Cited by 16 · see citing works
Self-citationReversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP)
Guarini, S., Bazzani, C., Tagliavini, S., Bertolini, A., & Ferrari, W. (1992) · Cellular and Molecular Life Sciences · doi:10.1007/bf02118314 · Cited by 9 · see citing works
Self-citationCainazzo, M. M., Ferrazza, G., Mioni, C., Bazzani, C., Bertolini, A., & Guarini, S. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01487-5 · Cited by 8 · see citing works
Self-citationBazzani, C., Balugani, A., Bertolini, A., & Guarini, S. (1993) · Resuscitation · doi:10.1016/0300-9572(93)90118-a · Cited by 6 · see citing works
Self-citationACTH analogue in treatment of acute aortic dissection
Olsson, C. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07348-8 · Cited by 5 · see citing works
ACTH analogue in treatment of acute aortic dissection-Authors' reply.
Noera, G., Lamarra, M., Guarini, S., & Bertolini, A. (2002) · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Physiology and immunology of the cholinergic antiinflammatory pathway
Tracey, K. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30555 · Cited by 1,563 · see citing works
The vagus nerve and the inflammatory reflex – linking immunity and metabolism
Pavlov, V. A., & Tracey, K. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.189 · Cited by 1,040 · see citing works
Mechanisms and Therapeutic Relevance of Neuro-immune Communication
Chavan, S. S., Pavlov, V. A., & Tracey, K. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.008 · Cited by 661 · see citing works
Cholinergic control of inflammation
Rosas‐Ballina, M., & Tracey, K. J. (2009) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2009.02098.x · Cited by 582 · see citing works
The cholinergic anti-inflammatory pathway
Pavlov, V. A., & Tracey, K. J. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2005.03.015 · Cited by 622 · see citing works
The vagus nerve and the nicotinic anti-inflammatory pathway
Ulloa, L. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1797 · Cited by 467 · see citing works
Molecular and functional neuroscience in immunity
Pavlov, V. A., Chavan, S. S., & Tracey, K. J. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053158 · Cited by 444 · see citing works
Huston, J. M., & Tracey, K. J. (2010) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02321.x · Cited by 342 · see citing works
Pavlov, V. A., & Tracey, K. J. (2015) · Immunologic Research · doi:10.1007/s12026-015-8718-1 · Cited by 254 · see citing works
Autonomic neural regulation of immunity
CZURA, C. J., & TRACEY, K. J. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01442.x · Cited by 255 · see citing works
Cytokines and the immunomodulatory function of the vagus nerve
Johnston, G. R., & Webster, N. R. (2009) · British Journal of Anaesthesia · doi:10.1093/bja/aep037 · Cited by 201 · see citing works
Neuro-immune interactions via the cholinergic anti-inflammatory pathway
Gallowitsch‐Puerta, M., & Pavlov, V. A. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.01.002 · Cited by 172 · see citing works
Boer, M. M. B.-D., van Wetten, M.-L., & Pruimboom, L. (2012) · Nutrition & Metabolism · doi:10.1186/1743-7075-9-32 · Cited by 166 · see citing works
Mioni, C., Bazzani, C., Giuliani, D., Altavilla, D., Leone, S., Ferrari, A., Minutoli, L., Bitto, A., Marini, H., Zaffe, D., et al. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000186762.05301.13 · Cited by 148 · see citing works
Self-citationRetractedNeuroprotective actions of melanocortins: a therapeutic opportunity
Catania, A. P. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.04.002 · Cited by 138 · see citing works
Wang, X., Yang, Z., Xue, B., & Shi, H. (2011) · Endocrinology · doi:10.1210/en.2010-0855 · Cited by 126 · see citing works
Chen, S., Zhao, L., Sherchan, P., Ding, Y., Yu, J., Nowrangi, D., Tang, J., Xia, Y., & Zhang, J. H. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1140-6 · Cited by 122 · see citing works
Distribution and Function of Melanocortin Receptors within the Brain
Mountjoy, K. G. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6354-3_3 · Cited by 114 · see citing works
Giuliani, D., Mioni, C., Altavilla, D., Leone, S., Bazzani, C., Minutoli, L., Bitto, A., Cainazzo, M. M., Marini, H. R., Zaffe, D., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0692 · Cited by 111 · see citing works
Self-citationSilverman, H. A., Dancho, M. E., Regnier‐Golanov, A., Nasim, M. M., Ochani, M., Olofsson, P. S., Ahmed, M., Miller, E. J., Chavan, S. S., Golanov, E. V., et al. (2014) · Molecular Medicine · doi:10.2119/molmed.2014.00147 · Cited by 110 · see citing works
Altavilla, D., Guarini, S., Bitto, A., Mioni, C., Giuliani, D., Bigiani, A., Squadrito, G., Minutoli, L., Venuti, F. S., Messineo, F., et al. (2006) · Shock · doi:10.1097/01.shk.0000209539.91553.82 · Cited by 98 · see citing works
Self-citationBrain effects of melanocortins☆
BERTOLINI, A., Tacchi, R., & Vergoni, A. V. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.10.005 · Cited by 98 · see citing works
The melanocortin system in leukocyte biology
Catania, A. P. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0706426 · Cited by 98 · see citing works
Chang, E. H., Chavan, S. S., & Pavlov, V. A. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00263 · Cited by 96 · see citing works
The renaissance of corticotropin therapy in proteinuric nephropathies
Gong, R. (2011) · Nature Reviews Nephrology · doi:10.1038/nrneph.2011.190 · Cited by 96 · see citing works
Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors
Zaghloul, N., Addorisio, M. E., Silverman, H. A., Patel, H. L., Valdés-Ferrer, S. I., Ayasolla, K. R., Lehner, K. R., Olofsson, P. S., Nasim, M., Metz, C. N., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01673 · Cited by 89 · see citing works
The, F., Cailotto, C., van der Vliet, J., de Jonge, W. J., Bennink, R. J., Buijs, R. M., & Boeckxstaens, G. E. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01296.x · Cited by 89 · see citing works
The Role of the Vagus Nerve in Cancer Prognosis: A Systematic and a Comprehensive Review
Couck, M., Caers, R., Spiegel, D., & Gidron, Y. (2018) · Journal of Oncology · doi:10.1155/2018/1236787 · Cited by 86 · see citing works
Huston, J. M. (2012) · Surgical Infections · doi:10.1089/sur.2012.126 · Cited by 85 · see citing works
VAN WESTERLOO, D. J., GIEBELEN, I. A. J., MEIJERS, J. C. M., DAALHUISEN, J., DE VOS, A. F., LEVI, M., & VAN DER POLL, T. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.02112.x · Cited by 84 · see citing works
Vagal-Immune Interactions Involved in Cholinergic Anti-Inflammatory Pathway
Žila, I., Mokrá, D., Kopincová, J., Kolomaznik, M., Javorka, M., & Čalkovská, A. (2017) · Physiological Research · doi:10.33549/physiolres.933671 · Cited by 80 · see citing works
Xia, Z., Liu, M., Wu, Y., Sharma, V. S., Luo, T., Ouyang, J., & McNeill, J. H. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.08.044 · Cited by 75 · see citing works
Experimental Therapeutic Strategies for Severe Sepsis
Parrish, W. R., Gallowitsch‐Puerta, M., Czura, C. J., & Tracey, K. J. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1418.011 · Cited by 68 · see citing works
Role of α-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation
Lasaga, M., Debéljuk, L., Durand, D., Scimonelli, T. N., & Caruso, C. M. (2008) · Peptides · doi:10.1016/j.peptides.2008.06.009 · Cited by 67 · see citing works
From CNI-1493 to the immunological homunculus: physiology of the inflammatory reflex
Oke, S. L., & Tracey, K. J. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0607363 · Cited by 67 · see citing works
Hiramoto, T., Chida, Y., Sonoda, J., Yoshihara, K., Sudo, N., & Kubo, C. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.005 · Cited by 66 · see citing works
Ottani, A., Giuliani, D., Mioni, C., Galantucci, M., Minutoli, L., Bitto, A., Altavilla, D., Zaffe, D., Botticelli, A. R., Squadrito, F., et al. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2008.140 · Cited by 65 · see citing works
Self-citationRetractedCholinergic Regulatory Lymphocytes Re-Establish Neuromodulation of Innate Immune Responses in Sepsis
Peña, G., Cai, B., Ramos, L., Vida, G., Deitch, E. A., & Ulloa, L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100013 · Cited by 61 · see citing works
Cholinergic modulation of inflammation.
Pavlov, V. A. (2008) · PubMed Central · Cited by 59 · see citing works
Metz, C. N., & Pavlov, V. A. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00195.2018 · Cited by 60 · see citing works
Treating disorders across the lifespan by modulating cholinergic signaling with galantamine
Metz, C. N., & Pavlov, V. A. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15243 · Cited by 56 · see citing works
Spaccapelo, L., Bitto, A., Galantucci, M., Ottani, A., Irrera, N., Minutoli, L., Altavilla, D., Novellino, E., Grieco, P., Zaffe, D., et al. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.09.015 · Cited by 55 · see citing works
Self-citationThe role of the vagus nerve in stroke
Mravec, B. (2010) · Autonomic Neuroscience · doi:10.1016/j.autneu.2010.08.009 · Cited by 52 · see citing works
Is neuroimmunomodulation a future therapeutic approach for sepsis?
Kumar, V., & Sharma, A. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.10.003 · Cited by 50 · see citing works
Mravec, B., Gidron, Y., & Hulín, I. (2007) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2007.12.002 · Cited by 47 · see citing works
Multiple Sclerosis, Relapses, and the Mechanism of Action of Adrenocorticotropic Hormone
Ross, A. P., Ben‐Zacharia, A. B., Harris, C. J., & Smrtka, J. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00021 · Cited by 46 · see citing works
Joshi, A. K. R., & Rajini, P. S. (2010) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2010.07.003 · Cited by 46 · see citing works
The Present and Future of Vagus Nerve Stimulation
Yang, J., & Phi, J. H. (2019) · Journal of Korean Neurosurgical Society · doi:10.3340/jkns.2019.0037 · Cited by 46 · see citing works
Giuliani, D., Mioni, C., Bazzani, C., Zaffe, D., Botticelli, A., Capolongo, S., Sabba, A., Galantucci, M., Iannone, A., Grieco, P., et al. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707115 · Cited by 45 · see citing works
Self-citationNeuroprotection in focal cerebral ischemia owing to delayed treatment with melanocortins
Giuliani, D., Ottani, A., Mioni, C., Bazzani, C., Galantucci, M., Minutoli, L., Bitto, A., Zaffe, D., Botticelli, A. R., Squadrito, F., et al. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.05.025 · Cited by 44 · see citing works
Self-citationNeural reflex pathways in intestinal inflammation: hypotheses to viable therapy
Willemze, R. A., Luyer, M. D. P., Buurman, W. A., & de Jonge, W. J. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.56 · Cited by 41 · see citing works
Wang, D., Zhou, R., & Yao, Y.-M. (2009) · PubMed · Cited by 41 · see citing works
Zheng, W., Huang, L., Zhao, L., Wang, B., Hui-bin, X., Wang, G., Wang, Z., & Zhou, H. (2008) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2007.02.007 · Cited by 41 · see citing works
Giuliani, D., Leone, S., Mioni, C., Bazzani, C., Zaffe, D., Botticelli, A. R., Altavilla, D., Galantucci, M., Minutoli, L., Bitto, A., et al. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.03.038 · Cited by 40 · see citing works
Self-citationBrunetti, L., Leone, S., Orlando, G., Ferrante, C., Recinella, L., Chiavaroli, A., Nisio, C. D., Shohreh, R., Manippa, F., Ricciuti, A., et al. (2014) · Pharmacological Reports · doi:10.1016/j.pharep.2014.06.014 · Cited by 38 · see citing works
Giuliani, D., Ottani, A., Neri, L., Zaffe, D., Grieco, P., Jochem, J., Cavallini, G. M., Catania, A., & Guarini, S. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.11.004 · Cited by 38 · see citing works
Self-citationRole of the brain melanocortins in blood pressure regulation
do Carmo, J. M., da Silva, A. A., Wang, Z., Fang, T., Aberdein, N., Perez de Lara, C. E., & Hall, J. E. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.03.003 · Cited by 38 · see citing works
Ottani, A., Giuliani, D., Galantucci, M., Spaccapelo, L., Novellino, E., Grieco, P., Jochem, J., & Guarini, S. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.03.052 · Cited by 38 · see citing works
Self-citationMelanocortins as potential therapeutic agents in severe hypoxic conditions
Giuliani, D., Minutoli, L., Ottani, A., Spaccapelo, L., Bitto, A., Galantucci, M., Altavilla, D., Squadrito, F., & Guarini, S. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.04.001 · Cited by 35 · see citing works
Self-citationAalbers, M. W., Klinkenberg, S., Rijkers, K., Verschuure, P., Kessels, A. G. H., Aldenkamp, A. P., Vles, J. S. H., & Majoie, M. (2012) · NeuroImmunoModulation · doi:10.1159/000341402 · Cited by 35 · see citing works
The clinical importance of the anti-inflammatory vagovagal reflex.
Boeckxstaens, G. (2013) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-53491-0.00011-0 · Cited by 29 · see citing works
Melanocortins and the Cholinergic Anti-Inflammatory Pathway
Giuliani, D., Ottani, A., Altavilla, D., Bazzani, C., Squadrito, F., & Guarini, S. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6354-3_6 · Cited by 34 · see citing works
Self-citationGiuliani, D., Ottani, A., Minutoli, L., Stefano, V. D., Galantucci, M., Bitto, A., Zaffe, D., Altavilla, D., Botticelli, A. R., Squadrito, F., et al. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.03.009 · Cited by 34 · see citing works
Self-citationAkıncı, S. B., Ulu, N., Yöndem, Ö. Z., Firat, P., Güc, M. O., Kanbak, M., & Aypar, Ü. (2005) · World Journal of Surgery · doi:10.1007/s00268-005-0073-2 · Cited by 33 · see citing works
Sun, L., Zhang, G.-F., Zhang, X., Liu, Q., Liu, J.-G., Su, D., & Liu, C. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.26 · Cited by 33 · see citing works
Minutoli, L., Bitto, A., Squadrito, F., Irrera, N., Rinaldi, M., Nicòtina, P. A., Arena, S., Magno, C., Marini, H. R., Spaccapelo, L., et al. (2011) · Endocrinology · doi:10.1210/en.2011-1016 · Cited by 33 · see citing works
Self-citationOttani, A., Galantucci, M., Ardimento, E., Neri, L., Canalini, F., Calevro, A., Zaffe, D., Novellino, E., Grieco, P., Giuliani, D., et al. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.03.005 · Cited by 32 · see citing works
Self-citationCorander, M. P., Fenech, M., & Coll, A. P. (2009) · Circulation · doi:10.1161/circulationaha.109.854612 · Cited by 31 · see citing works
Melanocortins Defend their Territory: Multifaceted Neuroprotection in Cerebral Ischemia
Tatro, J. B. (2006) · Endocrinology · doi:10.1210/en.2005-1573 · Cited by 31 · see citing works
Reduction of ischemic stroke in rat brain by alpha melanocyte stimulating hormone
Chen, G., Frøkiær, J., Pedersen, M., Nielsen, S. D.-H., Si, Z., Pang, Q., & Stødkilde‐Jørgensen, H. (2008) · Neuropeptides · doi:10.1016/j.npep.2008.01.004 · Cited by 27 · see citing works
The Vagus Nerve Attenuates Fulminant Hepatitis by Activating the Src Kinase in Kuppfer Cells
Li, Y., Xu, Z., Yu, Y., Yuan, H., Xu, H., Zhu, Q., Wang, C., & Shi, X. (2013) · Scandinavian Journal of Immunology · doi:10.1111/sji.12141 · Cited by 27 · see citing works
Disease-modifying anti-rheumatic drugs improve autonomic neuropathy in arthritis: DIANA study
Syngle, A., Verma, I., Krishan, P., Garg, N. B., & Syngle, V. (2014) · Clinical Rheumatology · doi:10.1007/s10067-014-2716-x · Cited by 26 · see citing works
Melanocortins protect against multiple organ dysfunction syndrome in mice
Bitto, A., Polito, F., Altavilla, D., Irrera, N., Giuliani, D., Ottani, A., Minutoli, L., Spaccapelo, L., Galantucci, M., Lodi, R., et al. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01098.x · Cited by 27 · see citing works
Self-citationMravec, B., Gidron, Y., Kukanova, B., Bízik, J., Kiss, A., & Hulín, I. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.07.003 · Cited by 26 · see citing works
Pulmonary arterial hypertension: the case for a bioelectronic treatment
Ntiloudi, D., Qanud, K., Tomaio, J. N., Giannakoulas, G. A., Al‐Abed, Y., & Zanos, S. P. (2019) · Bioelectronic Medicine · doi:10.1186/s42234-019-0036-9 · Cited by 23 · see citing works
Minutoli, L., Squadrito, F., Nicòtina, P. A., Giuliani, D., Ottani, A., Polito, F., Bitto, A., Irrera, N., Guzzo, G., Spaccapelo, L., et al. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e318207ea80 · Cited by 24 · see citing works
Self-citationRetractedNon-Canonical Effects of ACTH: Insights Into Adrenal Insufficiency
Hasenmajer, V., Bonaventura, I., Minnetti, M., Sada, V., Sbardella, E., & Isidori, A. M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.701263 · Cited by 23 · see citing works
Effects of Nicotine and Vagus Nerve in Severe Acute Pancreatitis–Associated Lung Injury in Rats
Ma, P., Yu, K., Yu, J., Wang, W., Ding, Y., Chen, C., Chen, X., Zhao, K., Zuo, T., He, X., et al. (2015) · Pancreas · doi:10.1097/mpa.0000000000000575 · Cited by 18 · see citing works
Ottani, A., Giuliani, D., Neri, L., Calevro, A., Canalini, F., Vandini, E., Cainazzo, M. M., Ruberto, A. I., Barbieri, A., Rossi, R., et al. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.10.022 · Cited by 17 · see citing works
Self-citationExtrahepatic factors in hepatic immune regulation
Zhang, S., Lu, S., & Li, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.941721 · Cited by 17 · see citing works
Organophosphorus Insecticides and Glucose Homeostasis
Joshi, A. K. R., & Rajini, P. S. (2012) · InTech eBooks · doi:10.5772/28721 · Cited by 15 · see citing works
Adrenocorticotropic hormone analog use for podocytopathies
Filippone, E. J., Dopson, S. J., Rivers, D. M., Monk, R. D., Udani, S., Jafari, G., Huang, S., Melhem, A., Assioun, B., & Schmitz, P. G. (2016) · International Medical Case Reports Journal · doi:10.2147/imcrj.s104899 · Cited by 15 · see citing works
Galantamine ameliorates hyperoxia-induced brain injury in neonatal mice
Zaghloul, N., Cohen, N. S., Ayasolla, K., Li, H.-L., Kurepa, D., & Ahmed, M. N. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.890015 · Cited by 14 · see citing works
Molecular Changes Induced in Rat Liver by Hemorrhage and Effects of Melanocortin Treatment
Lonati, C., Sordi, A., Giuliani, D., Spaccapelo, L., Leonardi, P., Carlin, A., Ottani, A., Galantucci, M., Grieco, P., Catania, A. P., et al. (2012) · Anesthesiology · doi:10.1097/aln.0b013e318246ea68 · Cited by 14 · see citing works
Self-citationRezende-Neto, J., Alves, R. L., de Carvalho, M. G., Almeida, T., Trant, C. G. M. C., Kushmerick, C., de Andrade, M. V. M., Rizoli, S., & Cunha-Melo, J. R. (2014) · Journal of Trauma Management & Outcomes · doi:10.1186/1752-2897-8-15 · Cited by 14 · see citing works
The Neuroimmune Communicatome in Inflammation
Olofsson, P. S., Metz, C. N., & Pavlov, V. A. (2017) · Wiley-VCH eBooks · doi:10.1002/9783527692156.ch59 · Cited by 14 · see citing works
Developments and new vistas in the field of melanocortins
Leone, S., Noera, G., & Bertolini, A. (2015) · BioMolecular Concepts · doi:10.1515/bmc-2015-0023 · Cited by 13 · see citing works
Lonati, C., Gatti, S., & Catania, A. P. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.569241 · Cited by 13 · see citing works
Gaidhani, N., & Uteshev, V. V. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.09.001 · Cited by 13 · see citing works
Electroacupuncture Protects against CCK-Induced Acute Pancreatitis in Rats
An, H., Lee, J., Lee, H., Yang, W. M., Park, S.-K., Hong, S.-H., Kim, H., & Um, J. (2007) · NeuroImmunoModulation · doi:10.1159/000107793 · Cited by 11 · see citing works
Yalçın, M., Savcı, V., & Jochem, J. (2009) · PubMed · Cited by 11 · see citing works
Subarachnoid Hemorrhage With Neurocardiogenic Stunning
Rose, J. J., Vanhecke, T. E., & McCullough, P. A. (2010) · Reviews in Cardiovascular Medicine · doi:10.3909/ricm0544 · Cited by 10 · see citing works
Liu, D., Zhang, H.-G., Chang, M., Li, Y., & Zhang, L.-Y. (2015) · Journal of Surgical Research · doi:10.1016/j.jss.2015.01.007 · Cited by 10 · see citing works
Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions
Copperi, F., Kim, J. D., & Diano, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.725709 · Cited by 9 · see citing works
Does vagus nerve constitute a self-organization complexity or a “hidden network”?
Mravec, B., & Hulín, I. (2006) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/bf03656776 · Cited by 8 · see citing works
Implications of a Local Overproduction of Tumor Necrosis Factor-α in Complex Regional Pain Syndrome
Walker, S., & Drummond, P. D. (2011) · Pain Medicine · doi:10.1111/j.1526-4637.2011.01273.x · Cited by 8 · see citing works
Hu, D., Li, J., Zhuang, Y., & Mao, X. (2021) · Steroids · doi:10.1016/j.steroids.2021.108930 · Cited by 7 · see citing works
Mravec, B. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.577086 · Cited by 7 · see citing works
Martins, C., Neves, L. T., de Oliveira, M. M. B. P., Bagatini, P. B., da Silva, R. B., Mestriner, R. G., Xavier, L. L., & Rasia‐Filho, A. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-74712-7 · Cited by 7 · see citing works
Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia
Jagdmann, S., Dames, C., Berchtold, D., Winek, K., Weitbrecht, L., Meisel, A., & Meisel, C. (2020) · Vaccines · doi:10.3390/vaccines8020253 · Cited by 6 · see citing works
- Authors
- GUARINI, S.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- GUARINI, S
- ORCID
- GUARINI, S
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-08
- Volume
- 63
- Issue
- 2
- Pages
- 357-365
- ISSN
- 0008-6363 (ISSN-L)
- OpenAlex
- W2122677936
- Cited by
- 131
- References
- 42
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 12
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Update notices
- expression_of_concern (2023-03-01)
- Open access
- bronze
- doi.org
- Locations
- Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
- Keywords
- ACTH, ACTH1-24, hemorrhagic shock, cholinergic anti-inflammatory pathway, vagus nerve, NF-κB, TNF-α, systemic inflammatory response, vagotomy, hypovolemia, resuscitation
- MeSH terms
- Acute Disease, Animals, Atropine, Chlorisondamine, Cosyntropin, Female, Liver, Male, Receptors, Nicotinic, RNA, Messenger, Shock, Hemorrhagic, Tumor Necrosis Factor-alpha, Vagus Nerve, NF-kappa B, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, I-kappa B Proteins, Electrophoretic Mobility Shift Assay, Rats
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