Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats (original) (raw)
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Does hepatic vagus nerve modulate the progression of biliary fibrosis in rats?
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Recent studies have shown that vagus nerve activation inhibits cytokine production in a variety of non-neural cells though activation of α7 nicotinic acetylcholine receptor (α7nAChR). Since chronic inflammation plays a pivotal role in liver fibrosis, this study was designed to investigate the role of hepatic vagus nerve in the progression of hepatic fibrosis in rats. Cirrhosis was induced by chronic ligation of the bile duct. Hepatic hydroxyproline level, portal pressure, serum transaminase level, hepatic TIMP-1 (tissue inhibitor of metalloproteinase-1) and MCP-1 (monocyte chemoattractant peptide-1) expression were measured in order to assess the progression of liver cirrhosis. α7nAChR expression was assessed using RT-PCR as well as immunostaining. RT-PCR analysis of the liver showed that α7nAChR mRNA is expressed in rat liver. Immunostaining study demonstrated that hepatic α7nAChR is mainly expressed in the hepatocytes of cirrhotic liver with minimum α7nAChR expression in biliary e...
Vasoactive intestinal peptide attenuates concanavalin A-mediated liver injury
European Journal of Pharmacology, 2009
Vasoactive intestinal peptide (VIP) is well characterized as an endogenous anti-inflammatory neuropeptide and has a brand range of biological functions. In this study, we found increased endogenous VIP expression in mice with concanavalin A-induced hepatitis, a widely used experimental model of immune-mediated liver injury. We investigated further the effect of VIP administration on concanavalin A-induced liver injury. Compared with mice pretreated with PBS, mice pretreated with VIP exhibited much lower plasma levels of aminotransferases, less inflammatory infiltration in the liver and hepatocyte apoptosis. Meanwhile, VIP significantly inhibited the release of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in concanavalin A-injected mice, but markedly elevated the production of antiinflammatory cytokine interleukine-10 (IL-10). Further investigation demonstrated increased intracellular cAMP concentration after VIP administration, and showed that the protective effect of VIP on concanavalin Ainduced hepatitis was mediated mainly through VIP receptor 1 (VPAC 1). These results suggest that VIP is capable of attenuating immune-mediated liver injury in vivo. This effect is associated with its downregulation of critical inflammatory mediators and its upregulation of anti-inflammatory cytokine through VPAC 1 , possibly via the cAMP-dependent pathway.
Loss of vagal anti-inflammatory effect: in vivo visualization and adoptive transfer
AJP: Regulatory, Integrative and Comparative Physiology, 2009
The vagus nerve is a conduit for bidirectional signaling between the brain and the viscera. Vagal signaling has been shown to downregulate gastrointestinal inflammation, and the mechanism is thought to involve acetylcholine binding to the alpha-7 subunit of the nicotinic acetylcholine receptor on macrophages. The aims of this study were to quantify the impact of vagotomy in vivo by visualizing nuclear factor (NF)-B activity and to determine if the proinflammatory impact of vagotomy could be transferred by lymphocytes. Real-time biophotonic imaging revealed that subdiaphragmatic vagotomy resulted in increased levels of NF-B in vivo. NF-B activation was further exaggerated in vivo following exposure to 4% DSS for 5 days. Vagotomized animals also exhibited higher disease activity scores and secreted more proinflammatory cytokines. Adoptive transfer of CD4 ϩ T cells from vagotomized animals (but not CD4 ϩ T cells from sham-operated controls) to naive dextran sulfate sodium (DSS)-treated recipients resulted in increased inflammatory scores. Further examination of the CD4 ϩ T cells revealed that adoptive transfer of the CD25 Ϫ population alone from vagotomized donors (but not sham-operated donors) was sufficient to aggravate colitis in DSS-treated recipients. Increased DSS-induced inflammation was associated with reduced CD4 ϩ CD25 ϩ Foxp3 ϩ regulatory T cell numbers in recipients. This study clearly demonstrates the ability of the vagus nerve to modulate activity of the proinflammatory transcription factor NF-B in vivo. The proinflammatory effect of vagotomy is transferable using splenic T cells and highlights a previously unappreciated cellular mechanism for linking central parasympathetic processes with mucosal inflammation and immune homeostasis. vagus nerve; murine models of colitis; nuclear factor-B; cytokines; regulatory T cells
An Effective Method for Acute Vagus Nerve Stimulation in Experimental Inflammation
Frontiers in Neuroscience, 2019
Neural reflexes regulate inflammation and electrical activation of the vagus nerve reduces inflammation in models of inflammatory disease. These discoveries have generated an increasing interest in targeted neurostimulation as treatment for chronic inflammatory diseases. Data from the first clinical trials that use vagus nerve stimulation (VNS) in treatment of rheumatoid arthritis and Crohn's disease suggest that there is a therapeutic potential of electrical VNS in diseases characterized by excessive inflammation. Accordingly, there is an interest to further explore the molecular mechanisms and therapeutic potential of electrical VNS in a range of experimental settings and available genetic mouse models of disease. Here, we describe a method for electrical VNS in experimental inflammation in mice.
The Role of the Vagus Nerve: Modulation of the Inflammatory Reaction in Murine Polymicrobial Sepsis
Mediators of Inflammation, 2012
The particular importance of the vagus nerve for the pathophysiology of peritonitis becomes more and more apparent. In this work we provide evidence for the vagal modulation of inflammation in the murine model of colon ascendens stent peritonitis (CASP). Vagotomy significantly increases mortality in polymicrobial sepsis. This effect is not accounted for by the dilatation of gastric volume following vagotomy. As the stimulation of cholinergic receptors by nicotine has no therapeutic effect, the lack of nicotine is also not the reason for the reduced survival rate. In fact, increased septic mortality is a consequence of the absent modulating influence of the vagus nerve on the immune system: we detected significantly elevated serum corticosterone levels in vagotomised mice 24 h following CASP and a decreased ex vivo TNF-alpha secretion of Kupffer cells upon stimulation with LPS. In conclusion, the vagus nerve has a modulating influence in polymicrobial sepsis by attenuating the immune dysregulation.
Mechanosensitive duodenal afferents contribute to vagal modulation of inflammation in the rat
The Journal of physiology, 2004
Noxious stimuli inhibit inflammation by activating neuroendocrine stress axes, an effect that is potently attenuated by ongoing activity in subdiaphragmatic vagal afferents. Because this vagal afferent activity is carried in the coeliac and coeliac accessory branches of the subdiaphragmatic vagus, we tested the hypothesis that the activity arises from vagal afferents that innervate a proximal segment of the gastrointestinal tract. Surgical removal of the duodenum, but not the stomach, produces a marked (six orders of magnitude) leftward shift in the dose-response curve for intraplantar capsaicin-induced inhibition of synovial plasma extravasation induced by the potent inflammatory mediator bradykinin, in the knee joint; this is similar in magnitude to the inhibition produced by subdiaphragmatic or by coeliac plus coeliac accessory branch vagotomy. Fasting, to unload mechanically sensitive polymodal afferents in the proximal gastrointestinal tract, produces a similar leftward shift i...
Bioelectronic Medicine, 2020
Background Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation. Methods Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and mea...