scholarly journals Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

2020 ◽  
Author(s):  
Byung Gon Jo ◽  
Uk Namgung
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Concanavalin A ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Liver Macrophages ◽  
Afferent Fibers ◽  
Tnf Α ◽  
Hepatic Branch ◽  
Anti Inflammation

Abstract Background: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods: An animal model of hepatitis was generated by intraperitoneal injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN was selectively eliminated by treating animals with capsaicin (CAP). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining.Results: TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). hVNS also induced an increase in phospho-STAT3 in the liver macrophages of ConA-injected animals, suggesting the activation of STAT3 transcription factor associated with cholinergic anti-inflammation. Capsaicin (CAP) treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and also induced an increase in apoptotic caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was reduced by CAP administration. Conclusions: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

scholarly journals Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Byung Gon Jo ◽  
Seung-Hyung Kim ◽  
Uk Namgung
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Concanavalin A ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Α7 Nachr ◽  
Afferent Fibers ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Hepatic Branch

Abstract Background Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods An animal model of hepatitis was generated by intraperitoneal (i.p.) injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN activity was regulated by administration of capsaicin (CAP) or AP-5/CNQX and the vagotomy at the hepatic branch of the vagus nerve (hVNX). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining. Hepatic immune cells were analyzed by flow cytometry. Results TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). Alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum and the number of hepatic CD4+ and CD8+ T cells were increased by ConA injection and downregulated by hVNS. CAP treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and increased caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was hampered by CAP treatment and similarly regulated by hVNX and AP-5/CNQX inhibition of vagal feedback loop pathway in the brainstem. hVNS elevated the levels of α7 nicotinic acetylcholine receptors (α7 nAChR) and phospho-STAT3 (Tyr705; pY-STAT3) in the liver, and inhibition of AFVN activity by CAP, AP-5/CNQX and hVNX or the pharmacological blockade of hepatic α7 nAChR decreased STAT3 phosphorylation. Conclusions Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

scholarly journals Vagal afferent fibers contribute to the anti-inflammatory reactions by vagus nerve stimulation in concanavalin A model of hepatitis in rats

2020 ◽  
Author(s):  
Byung Gon Jo ◽  
Seung-Hyung Kim ◽  
Uk Namgung
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Concanavalin A ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Afferent Fibers ◽  
Stat3 Phosphorylation ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Hepatic Branch

Abstract Background: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods: An animal model of hepatitis was generated by intraperitoneal (i.p.) injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN activity was regulated by administration of capsaicin (CAP) or AP-5/CNQX and the vagotomy at the hepatic branch of the vagus nerve (hVNX). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining. Hepatic immune cells were analyzed by flow cytometry.Results: TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). Alanine transaminase (ALT) and aspartate transaminase (AST) levels in serum and the number of hepatic CD4+ and CD8+ T cells were increased by ConA injection and downregulated by hVNS. CAP treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and increased caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was hampered by CAP treatment and similarly regulated by hVNX and AP-5/CNQX inhibition of vagal feedback loop pathway in the brainstem. hVNS elevated the levels of a7 nicotinic acetylcholine receptors (a7 nAChR) and phospho-STAT3 (Tyr705; pY-STAT3) in the liver, and inhibition of AFVN activity by CAP, AP-5/CNQX and hVNX or the pharmacological blockade of hepatic a7 nAChR decreased STAT3 phosphorylation. Conclusions: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

scholarly journals Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yong-Mei Wang ◽  
Ya-Yun Xu ◽  
Yi Zhai ◽  
Qian-Qian Wu ◽  
Wen Huang ◽  
...  
Keyword(s):  
Treatment Group ◽  
Sleep Quality ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Alcohol Withdrawal ◽  
Vagus Nerve Stimulation ◽  
Control Group ◽  
Depression Symptoms ◽  
Tnf Α ◽  
Alcohol Dependent

Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.

scholarly journals Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations

2020 ◽  
Author(s):  
Omer Sharon ◽  
Firas Fahoum ◽  
Yuval Nir
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pupil Dilation ◽  
Somatosensory Stimulation ◽  
Alpha Oscillations ◽  
Sham Stimulation ◽  
Non Invasive ◽  
Transcutaneous Vagus Nerve Stimulation

AbstractVagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS), which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent that tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.Significance statementCurrent non-invasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating-current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4s) tVNS pulses in naïve healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus-noradrenaline signaling, and support the notion that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying the means by which endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.

scholarly journals Men Show Reduced Cardiac Baroreceptor Sensitivity during Modestly Painful Electrical Stimulation of the Forearm: Exploratory Results from a Sham-Controlled Crossover Vagus Nerve Stimulation Study

2021 ◽  
Vol 18 (21) ◽  
pp. 11193
Author(s):  
Elisabeth Veiz ◽  
Susann-Kristin Kieslich ◽  
Julia Staab ◽  
Dirk Czesnik ◽  
Christoph Herrmann-Lingen ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Hemodynamic Parameters ◽  
Baroreceptor Sensitivity ◽  
Young Males ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
Post Hoc ◽  
Stimulation Of

This paper presents data from a transcutaneous vagus nerve stimulation experiment that point towards a blunted cardiac baroreceptor sensitivity (cBRS) in young males compared to females during electrical stimulation of the forearm and a rhythmic breathing task. Continuous electrocardiography, impedance cardiography and continuous blood-pressure recordings were assessed in a sex-matched cohort of twenty young healthy subjects. Electrical stimulation of the median nerve was conducted by using a threshold-tracking method combined with two rhythmic breathing tasks (0.1 and 0.2 Hz) before, during and after active or sham transcutaneous vagus nerve stimulation. Autonomic and hemodynamic parameters were calculated, and differences were analyzed by using linear mixed models and post hoc F-tests. None of the autonomic and hemodynamic parameters differed between the sham and active conditions. However, compared to females, male participants had an overall lower total cBRS independent of stimulation condition during nerve stimulation (females: 14.96 ± 5.67 ms/mmHg, males: 11.89 ± 3.24 ms/mmHg, p = 0.031) and rhythmic breathing at 0.2 Hz (females: 21.49 ± 8.47 ms/mmHg, males: 15.12 ± 5.70 ms/mmHg, p = 0.004). Whereas vagus nerve stimulation at the left inner tragus did not affect the efferent vagal control of the heart, we found similar patterns of baroreceptor sensitivity activation over the stimulation period in both sexes, which, however, significantly differed in their magnitude, with females showing an overall higher cBRS.

scholarly journals Vagus nerve stimulation in chronic refractory epilepsy: chasing the cardiologist

2021 ◽  
Author(s):  
Ansh Chaudhary ◽  
Bhupendra Chaudhary
Keyword(s):  
Electrical Stimulation ◽  
Vagus Nerve ◽  
Antiepileptic Drugs ◽  
Nerve Stimulation ◽  
Side Effect ◽  
Neurological Disorder ◽  
Vagus Nerve Stimulation ◽  
Refractory Epilepsy ◽  
Stimulation Of

Epilepsy the second most common chronic neurological disorder after stroke affect 0.5-2% population worldwide. Antiepileptic drugs though remain the corner stone in management of epilepsy in majority of patients but still 30% of patients continues to have seizure or experience unacceptable pharmacological side effect. Electrical stimulation of vagus nerve is an effective and promising neurophysiological treatment for patients with refractory epilepsy who are either unsuitable candidate of surgery or falls in category of surgically refractory epilepsy. 

scholarly journals Vagus Nerve Stimulation Decreases Pancreatitis Severity in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Luyao Zhang ◽  
Zhiyang Wu ◽  
Zhihui Tong ◽  
Qi Yao ◽  
Ziyu Wang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Nicotinic Acetylcholine Receptors ◽  
Adoptive Transfer ◽  
Vagus Nerve Stimulation ◽  
Survival Rates ◽  
Neural Activation ◽  
Duct Ligation ◽  
Tnf Α

BackgroundVagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP).MethodsTwo independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR+ macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS.ResultsVNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR+ macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS.ConclusionsVNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.

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