scholarly journals Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jun-ying Wang ◽  
Yue Zhang ◽  
Yu Chen ◽  
Yu Wang ◽  
Shao-yuan Li ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Critical Role ◽  
Signal Pathway ◽  
Antidepressant Effect ◽  
Control Group ◽  
Mild Stress ◽  
Activated State ◽  
Regulated Expression

Abstract Background Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (−/−) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA). Methods There were control, model, taVNS, α7nAChR(−/−) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected. Results Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(−/−) rats and Hi MLA rats. Conclusion The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.

scholarly journals Antidepressant-like Effects of Transcutaneous Auricular Vagus Nerve Stimulation: Insights from Relieves Neuroinflammation Mediated by P2X7R in Rat Model of Chronic Unpredicted Mild Stress

2020 ◽  
Author(s):  
Yu Wang ◽  
Hong Meng ◽  
Shaoyuan Li ◽  
Xun He ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Body Weight ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Body Weight Loss ◽  
Preference Test ◽  
The Body ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Caspase 1

Abstract Background: As a prevalent mental health condition, depression is believed to be mediated by stress-induced neuroinflammation. Transcutaneous auricular vagus nerve stimulation (taVNS) has been used in the treatment of depression as the latest neuromodulation therapy. However, the antidepressant mechanism of the treatment at the molecular level is still unclear. Our previous study evaluated the effectiveness of the taVNS in antidepressant-like behavior. The objective of this study is to explore the role of P2X7R mediated hippocampal neuroinflammation in taVNS’s antidepressant effect. Methods: Rat depression model was established by using a chronic unpredicted mild stress (CUMS) method for five weeks. Starting from the 3rd week, taVNS intervention was applied through an electroacupuncture apparatus (HANS-100A, 2/15 Hz, 2mA) for 30 minutes every day for three weeks. Body weight test (BWT) and behavioral assessments such as open field test (OFT) and sucrose preference test (SPT) were conducted on days 0, 7, 14, 21, 28 and 35. The protein levels of P2X7R, NLRP3, caspase-1, IL-1β and IL-18 in the hippocampus were examined using western blot. Moreover, P2X7R expressing cells were detected using immunohistochemistry.Results: The results showed that CUMS induced body weight loss and depression-like behavior in rats. Hippocampal neuroinflammation was upregulated, which was manifested in the higher expression of P2X7R, NLRP3, caspase-1, IL-1β and IL-18. Interestingly, 3 weeks of the taVNS significantly reduced the depression-like behaviors and strengthen the growth of the body, and the CUMS-induced expression of P2X7R, NLRP3, caspase-1, IL-1β and IL-18 was attenuated. We also found that P2X7R was expressed in microglia of the hippocampus.Conclusion: In summary, the taVNS has antidepressant effect. It alleviates hippocampal neuroinflammation, which may be related to the regulation of the initial signal of P2X7R.

Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial

2014 ◽  
Author(s):  
Peijing Rong ◽  
Aihua Liu ◽  
Jianguo Zhang ◽  
Yuping Wang ◽  
Wei He ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Seizure Frequency ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Refractory Epilepsy ◽  
Controlled Trial ◽  
Control Group ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
Significant Difference

Abstract This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy. Pre-trial：144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment，the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks，according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks’ treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups, respectively, experienced reduction in seizure frequency that reached I, II and III levels according to the standards of the Modified Engel Scale compared with the baselines, indicating significant difference in seizure reduction between the two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction, and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction. After 8 weeks’ treatment, the percentages of average seizure frequency in ta-VNS and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a statistically significant difference in the results between the two groups (P<0.05). In addition, there were significant improvements in electroencephalograph (EEG) and the quality of daily life of the patients after treatment. The results show that this ta-VNS treatment can effectively reduce the frequency of seizures and improve the patient's quality of life. This may be an effective treatment for refractory epilepsy. At the same time，it is also safe，economic, and widely applicable.

Occipitoatlantal decompression and noninvasive vagus nerve stimulation slow conduction velocity through the atrioventricular node in healthy participants

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ariana S. Dalgleish ◽  
Adrienne M. Kania ◽  
Harald M. Stauss ◽  
Adrianna Z. Jelen
Keyword(s):  
Atrial Fibrillation ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Rate Control ◽  
Vagus Nerve Stimulation ◽  
Recovery Period ◽  
Atrioventricular Conduction ◽  
Ventricular Rate ◽  
Control Group ◽  
Baseline Recording

Abstract Context Management of atrial fibrillation includes either rhythm control that aims at establishing a sinus rhythm or rate control that aims at lowering the ventricular rate, usually with atrioventricular nodal blocking agents. Another potential strategy for ventricular rate control is to induce a negative dromotropic effect by augmenting cardiac vagal activity, which might be possible through noninvasive and nonpharmacologic techniques. Thus, the hypothesis of this study was that occipitoatlantal decompression (OA-D) and transcutaneous auricular vagus nerve stimulation (taVNS) not only increase cardiac parasympathetic tone as assessed by heart rate variability (HRV), but also slow atrioventricular conduction, assessed by the PQ-interval of the electrocardiogram (EKG) in generally healthy study participants without atrial fibrillation. Objectives To test whether OA-D and/or transcutaneous taVNS, which have been demonstrated to increase cardiac parasympathetic nervous system activity, would also elicit a negative dromotropic effect and prolong atrioventricular conduction. Methods EKGs were recorded in 28 healthy volunteers on three consecutive days during a 30 min baseline recording, a 15 min intervention, and a 30 min recovery period. Participants were randomly assigned to one of three experimental groups that differed in the 15 min intervention. The first group received OA-D for 5 min, followed by 10 min of rest. The second group received 15 min of taVNS. The intervention in the third group that served as a time control group (CTR) consisted of 15 min of rest. The RR- and PQ-intervals were extracted from the EKGs and then used to assess HRV and AV-conduction, respectively. Results The OA-D group had nine participants (32.1%), the taVNS group had 10 participants (35.7%), and the CTR group had nine participants (32.1%). The root mean square of successive differences between normal heartbeats (RMSSD), an HRV measure of cardiac parasympathetic modulation, tended to be higher during the recovery period than during the baseline recording in the OA-D group (mean ± standard error of the mean [SEM], 54.6 ± 15.5 vs. 49.8 ± 15.8 ms; p<0.10) and increased significantly in the taVNS group (mean ± SEM, 28.8 ± 5.7 vs. 24.7 ± 4.8 ms; p<0.05), but not in the control group (mean ± SEM, 31.4 ± 4.2 vs. 28.5 ± 3.8 ms; p=0.31). This increase in RMSSD was accompanied by a lengthening of the PQ-interval in the OA-D (mean ± SEM, 170.5 ± 9.6 vs. 166.8 ± 9.7 ms; p<0.05) and taVNS (mean ± SEM, 166.6 ± 6.0 vs. 162.1 ± 5.6 ms; p<0.05) groups, but not in the control group (mean ± SEM, 164.3 ± 9.2 vs. 163.1 ± 9.1 ms; p=0.31). The PQ-intervals during the baseline recordings did not differ on the three study days in any of the three groups, suggesting that the negative dromotropic effect of OA-D and taVNS did not last into the following day. Conclusions The lengthening of the PQ-interval in the OA-D and taVNS groups was accompanied by an increase in RMSSD. This implies that the negative dromotropic effects of OA-D and taVNS are mediated through an increase in cardiac parasympathetic tone. Whether these findings suggest their utility in controlling ventricular rates during persistent atrial fibrillation remains to be determined.

Vagus Nerve Stimulation Attenuates Early Traumatic Brain Injury by Regulating the NF-κB/NLRP3 Signaling Pathway

2020 ◽  
Vol 34 (9) ◽  
pp. 831-843
Author(s):  
Yunliang Tang ◽  
Xiaoyang Dong ◽  
Gengfa Chen ◽  
Wen Ye ◽  
Junwei Kang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vagus Nerve ◽  
Signaling Pathway ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Critical Role ◽  
Neurological Deficits ◽  
Receptor Protein

Background Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Oxidative stress, inflammation, and apoptosis are vital pathophysiological features post-TBI. Objectives Research has shown that vagus nerve stimulation (VNS) can attenuate oxidative stress in various diseases. However, the critical role of VNS in TBI is still not completely understood. This study investigated the protective effects and potential mechanism of VNS on TBI. Methods Male Sprague-Dawley rats were randomized into 3 groups: sham, TBI, and TBI + VNS. The TBI model was induced in rats by the free-fall drop method. The vagal nerve trunk was separated, and VNS was performed after establishing the TBI model. Results The results showed that VNS significantly ameliorated tissue damage, neurological deficits, and cerebral edema, compared with the sham VNS group. Additionally, VNS alleviated oxidative stress, inflammation, and apoptosis in the pericontusive cortex of rats after TBI. VNS also significantly suppressed expression of the nuclear factor-κB (NF-κB) protein in the nucleus and activation of the nucleotide-binding domain–like receptor protein 3 (NLRP3) inflammasome. Conclusions Taken together, the present study indicates that VNS may attenuate brain damage after TBI by inhibiting oxidative stress, inflammation, and apoptosis, possibly through the NF-κB/NLRP3 signaling pathway.

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.

Effect of Transcutaneous Vagus Nerve Stimulation in Dysphagia After Lateral Medullary Infarction: A Case Report

2019 ◽  
Vol 28 (4) ◽  
pp. 1381-1387
Author(s):  
Ying Yuan ◽  
Jie Wang ◽  
Dongyu Wu ◽  
Dahua Zhang ◽  
Weiqun Song
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Rating Scale ◽  
Tube Feeding ◽  
Nasogastric Feeding ◽  
Lateral Medullary Infarction ◽  
Severe Dysphagia ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
Medullary Infarction

Purpose Severe dysphagia with weak pharyngeal peristalsis after dorsal lateral medullary infarction (LMI) requires long-term tube feeding. However, no study is currently available on therapeutic effectiveness in severe dysphagia caused by nuclear damage of vagus nerve after dorsal LMI. The purpose of the present investigation was to explore the potential of transcutaneous vagus nerve stimulation (tVNS) to improve severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Method We assessed the efficacy of 6-week tVNS in a 28-year-old woman presented with persisting severe dysphagia after dorsal LMI who had been on nasogastric feeding for 6 months. tVNS was applied for 20 min twice a day, 5 days a week, for 6 weeks. The outcome measures included saliva spitted, Swallow Function Scoring System, Functional Oral Intake Scale, Clinical Assessment of Dysphagia With Wallenberg Syndrome, Yale Pharyngeal Residue Severity Rating Scale, and upper esophagus X-ray examination. Results After tVNS, the patient was advanced to a full oral diet without head rotation or spitting. No saliva residue was found in the valleculae and pyriform sinuses. Contrast medium freely passed through the upper esophageal sphincter. Conclusion Our findings suggest that tVNS might provide a useful means for recovery of severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Supplemental Material https://doi.org/10.23641/asha.9755438

Vagus nerve stimulation in rheumatoid arthritis – Authors' reply

2021 ◽  
Vol 3 (1) ◽  
pp. e14-e15
Author(s):  
Mark C Genovese ◽  
Yaakov A Levine ◽  
David Chernoff
Keyword(s):  
Rheumatoid Arthritis ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation
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