Transcutaneous Auricular Vagus Nerve Stimulation at 20 Hz Improves Depression-Like Behaviors and Down-Regulates the Hyperactivity of HPA Axis in Chronic Unpredictable Mild Stress Model Rats

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.

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

Journal of Neuroinflammation ◽

10.1186/s12974-021-02341-6 ◽

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.

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

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-18-0262 ◽

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

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Vagus Nerve Stimulation Cleared for Depression

Internal Medicine News ◽

10.1016/s1097-8690(05)71732-7 ◽

2005 ◽

Vol 38 (16) ◽

pp. 39

Author(s):

HEIDI SPLETE

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation

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Vagus nerve stimulation in rheumatoid arthritis – Authors' reply

The Lancet Rheumatology ◽

10.1016/s2665-9913(20)30357-x ◽

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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Vagus Nerve Stimulation Brings Hope for Those Living with Depression

PsycEXTRA Dataset ◽

10.1037/e567212006-010 ◽

2006 ◽

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation

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Cognition-enhancing effect of vagus nerve stimulation on refractory epilepsy secondary to lissencephaly: A case report.

Psychology & Neuroscience ◽

10.1037/pne0000120 ◽

2018 ◽

Vol 11 (1) ◽

pp. 80-85

Author(s):

Rodrigo Marmo da Costa e Souza ◽

Felipe Ricardo Pereira Vasconcelos De Arruda ◽

Jose Anderson Galdino Santos ◽

Jamerson De Carvalho Andrade ◽

Suellen Mary Marinho Dos Santos Andrade ◽

...

Keyword(s):

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Refractory Epilepsy ◽

Enhancing Effect

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Transcranial direct current stimulation (tDCS) in epilepsy patients with vagus nerve stimulation (VNS) therapy

Neuropediatrics ◽

10.1055/s-2008-1079529 ◽

2008 ◽

Vol 39 (01) ◽

Author(s):

I Orosz ◽

I König ◽

J Sperner

Keyword(s):

Vagus Nerve ◽

Direct Current ◽

Nerve Stimulation ◽

Transcranial Direct Current Stimulation ◽

Vagus Nerve Stimulation ◽

Direct Current Stimulation

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Implanted vagus nerve stimulation in 126 patients: surgical technique and complications

Perspectives in Surgery ◽

10.33699/pis.2020.99.7.304-310 ◽

2020 ◽

Vol 99 (7) ◽

Keyword(s):

Vagus Nerve ◽

Vocal Cord ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pulse Generator ◽

Operative Procedure ◽

Intractable Epilepsy ◽

Vagal Nerve ◽

University Hospital ◽

Nerve Stimulator

Introduction: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region. Methods: Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.1−58.4 years). Results: Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches. Conclusion: Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.

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