Transcutaneous Auricular Vagus Nerve Stimulation Protects Endotoxemic Rat from Lipopolysaccharide-Induced Inflammation

Background. Transcutaneous auricular vagus nerve stimulation (ta-VNS) could evoke parasympathetic activities via activating the brainstem autonomic nuclei, similar to the effects that are produced after vagus nerve stimulation (VNS). VNS modulates immune function through activating the cholinergic anti-inflammatory pathway.Methods. VNS, ta-VNS, or transcutaneous electrical acupoint stimulation (TEAS) on ST36 was performed to modulate the inflammatory response. The concentration of serum proinflammatory cytokines and tissue NF-kappa B p65 (NF-κB p65) were detected in endotoxaemia affected anesthetized rats.Results. Similar to the effect of VNS, ta-VNS suppressed the serum proinflammatory cytokines levels, such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as well as NF-kappa B p65 expressions of lung tissues. ST36 stimulation also decreases LPS-induced high TNF-αlevel and NF-κB signal, but it did not restrain proinflammatory cytokine IL-1βand IL-6. Neither ta-VNS nor ST36 stimulation could suppress LPS-induced TNF-αand NF-κB after vagotomy or withα7nAChR antagonist injection.Conclusions. The present paper demonstrated that ta-VNS could be utilized to suppress LPS-induced inflammatory responses viaα7nAChR-mediated cholinergic anti-inflammatory pathway.

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Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway

Neurogastroenterology & Motility ◽

10.1111/nmo.12076 ◽

2013 ◽

Vol 25 (3) ◽

pp. 208-221 ◽

Cited By ~ 136

Author(s):

B. Bonaz ◽

C. Picq ◽

V. Sinniger ◽

J. F. Mayol ◽

D. Clarençon

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Inflammatory Pathway ◽

Anti Inflammatory

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The cholinergic anti-inflammatory pathway in chronic kidney disease—review and vagus nerve stimulation clinical pilot study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa200 ◽

2020 ◽

Vol 35 (11) ◽

pp. 1840-1852

Author(s):

Marie Hilderman ◽

Annette Bruchfeld

Keyword(s):

Chronic Kidney Disease ◽

Pilot Study ◽

Kidney Disease ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Cell Injury ◽

Inflammatory Pathway ◽

Increased Risk ◽

Anti Inflammatory

Abstract Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro-immune circuit that upholds the homoeostatic balance of inflammatory activity in response to cell injury and pathogens. CAP models have been examined in preclinical studies to investigate its significance in a range of clinical inflammatory conditions and diseases. More recently, cervical vagus nerve stimulation (VNS) implants have been shown to be of potential benefit for patients with chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. We have previously shown that dialysis patients have a functional CAP ex vivo. Here we review the field and the potential role of the CAP in acute kidney injury and chronic kidney disease (CKD) as well as in hypertension. We also present a VNS pilot study in haemodialysis patients. Controlling inflammation by neuroimmune modulation may lead to new therapeutic modalities for improved treatment, outcome, prognosis and quality of life for patients with CKD.

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Transcutaneous Vagus Nerve Stimulation Regulates the Cholinergic Anti-inflammatory Pathway to Counteract 1, 2-Dimethylhydrazine Induced Colon Carcinogenesis in Albino wistar Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2019.00353 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 5

Author(s):

Jitendra K. Rawat ◽

Subhadeep Roy ◽

Manjari Singh ◽

Swetlana Guatam ◽

Rajnish K. Yadav ◽

...

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Wistar Rats ◽

Colon Carcinogenesis ◽

Inflammatory Pathway ◽

Transcutaneous Vagus Nerve Stimulation ◽

Anti Inflammatory

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Vagus nerve stimulation and the cholinergic anti-inflammatory pathway: A potential new therapeutic approach in inflammatory bowel diseases

Autonomic Neuroscience ◽

10.1016/j.autneu.2013.08.030 ◽

2013 ◽

Vol 177 (2) ◽

pp. 307

Author(s):

S. Clarençon ◽

V. Sinniger ◽

C. Picq ◽

S. Pellissier ◽

B. Bonaz

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Inflammatory Bowel Diseases ◽

Vagus Nerve Stimulation ◽

Therapeutic Approach ◽

Inflammatory Pathway ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Anti Inflammatory

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Non-invasive vagus nerve stimulation attenuates proinflammatory cytokines and augments antioxidant levels in the brainstem and forebrain regions of Dahl salt sensitive rats

Scientific Reports ◽

10.1038/s41598-020-74257-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Madhan Subramanian ◽

Laura Edwards ◽

Avery Melton ◽

Lyndee Branen ◽

Angela Herron ◽

...

Keyword(s):

Vagus Nerve ◽

Proinflammatory Cytokines ◽

Rat Model ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Antioxidant Properties ◽

Vagal Tone ◽

Brain Regions ◽

Cardiac Vagal Tone ◽

Anti Inflammatory

Abstract The anti-inflammatory effects of vagus nerve stimulation are well known. It has recently been shown that low-level, transcutaneous stimulation of vagus nerve at the tragus (LLTS) reduces cardiac inflammation in a rat model of heart failure with preserved ejection fraction (HFpEF). The mechanisms by which LLTS affect the central neural circuits within the brain regions that are important for the regulation of cardiac vagal tone are not clear. Female Dahl salt-sensitive rats were initially fed with either low salt (LS) or high salt (HS) diet for a period of 6 weeks, followed by sham or active stimulation (LLTS) for 30 min daily for 4 weeks. To study the central effects of LLTS, four brainstem (SP5, NAb, NTS, and RVLM) and two forebrain sites (PVN and SFO) were examined. HS diet significantly increased the gene expression of proinflammatory cytokines in the SP5 and SFO. LLTS reversed HS diet-induced changes at both these sites. Furthermore, LLTS augmented the levels of antioxidant Nrf2 in the SP5 and SFO. Taken together, these findings suggest that LLTS has central anti-inflammatory and antioxidant properties that could mediate the neuromodulation of cardiac vagal tone in the rat model of HFpEF.

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