Vagal nerve stimulation attenuates IL-6 and TNFα expression in respiratory regions of the developing rat brainstem

Johnson, Rhaya L; Murray, Samuel; Camacho, David K.; Wilson, Christopher G.

doi:10.1016/j.resp.2016.03.014

Cited by 22 publications

(13 citation statements)

References 12 publications

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“…Adoptive transfer of a7nAChR-positive splenocytes from VNS-treated wild-type mice, but not from a7nAChR-knockout mice, protected against kidney ischaemia-reperfusion injury [85], indicating a role for the a7nAChR in this mechanism. Another study showed that VNS may result in reduced expression of IL-6 and TNF in the brain of rats after LPS injection into the trachea, specifically in the nucleus tractus solitarii where the afferent vagus nerve terminates, indicating that VNS could also change cytokine expression centrally [86]. As noted above, afferent activation of the vagus nerve may also stimulate the HPA axis, leading to increased levels of plasma cortisol with an anti-inflammatory effect [48] (Fig.…”

Section: The Effects Of Vagus Nerve Stimulation On Inflammation In Humentioning

confidence: 80%

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

et al. 2017

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Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune‐mediated inflammatory disease (IMID). We recently discovered that autonomic dysfunction precedes and predicts arthritis development in subjects at risk of developing seropositive RA. In addition, RA patients with relatively high vagus nerve tone (higher parasympathetic parameters, measured by heart rate variability) respond better to antirheumatic therapies. Together, these data suggest that the ANS may control inflammation in humans. This notion is supported by experimental studies in animal models of RA. We have found that stimulation of the so‐called cholinergic anti‐inflammatory pathway by efferent electrical vagus nerve stimulation (VNS) or pharmacological activation of the alpha7 subunit of nicotinic acetylcholine receptors (α7nAChR) improves clinical signs and symptoms of arthritis, reduces cytokine production and protects against progressive joint destruction. Conversely, increased arthritis activity was observed in alpha7nAChR knockout mice. These studies together with previous work in animal models of sepsis and other forms of inflammation provided the rationale for an experimental clinical trial in patients with RA. We could for the first time show that an implantable vagus nerve stimulator inhibits peripheral blood cytokine production in humans. VNS significantly inhibited TNF and IL‐6 production and improved RA disease severity, even in some patients with therapy‐resistant disease. This work strongly supports further studies using a bioelectronic approach to treat RA and other IMIDs.

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Section: The Effects Of Vagus Nerve Stimulation On Inflammation In Humentioning

confidence: 80%

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

et al. 2017

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“…Brainstems were frozen in Tissue-Tek OCT and sectioned at 20μm on a Leica CM 3050S cryostat. Sections of brainstem were stained using immunohistochemistry with selective antibodies for IL-6 (1:100 sc-1265-r, Santa Cruz), TNFα (1:100 ab6671, Abcam), IL-1β (1:100 ab9722, Abcam) and HMGB-1 (1:1000 ab18256, Abcam) as previously described ( 22 ). The number of cells expressing IL-6, TNFα, IL-1β, and HMGB1 protein were counted using a Zeiss Axio Imager A1 and unbiased stereology ( Stereologer2000 , Stereology Resource Center).…”

Section: Methodsmentioning

confidence: 99%

Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates

et al. 2017

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BackgroundVagus Nerve Stimulation (VNS) is an FDA-approved method delivering electrical impulses for treatment of depression and epilepsy in adults. The vagus nerve innervates the majority of visceral organs and cervix, but potential impacts of VNS on the progress of pregnancy and the fetus are not well studied.MethodsWe tested the hypothesis that VNS in pregnant dams does not induce inflammatory changes in the cardiorespiratory control regions of the pups’ brainstem, potentially impacting the morbidity and mortality of offspring. Pregnant dams were implanted with stimulators providing intermittent low or high frequency electrical stimulation of the sub-diaphragmatic esophageal segment of the vagus nerve for 6–7 days until delivery. After birth, we collected pup brainstems that included cardio-respiratory control regions and counted the cells labeled for pro-inflammatory cytokines (IL-1β, IL-6, TNFα) and HMGB1.ResultsNeither pup viability nor number of cells labeled for pro-inflammatory cytokines in nTS nor XII was impaired by VNS. We provide evidence suggesting that chronic VNS of pregnant mothers does not impede the progress or outcome of pregnancy.ConclusionsVNS does not cause preterm birth, affect well-being of progeny, or impact central inflammatory processes that are critical for normal cardiovascular and respiratory function in newborns.

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“…In the present study, we show that VNS reduces the expression of IL-6 and TNFa in response to a brief (30 minute) bout of high-frequency VNS stimuli. 52 Our hope for this preclinical translational work is that it will eventually lead to minimally invasive VNS treatment to provide early intervention and reduce the likelihood of sepsis in preterm infants.…”

Section: Potential Uses and Mechanisms Of Vnsmentioning

confidence: 99%

“…Although VNS as currently used for epilepsy and depression can take months to show dramatic effect, short-term stimulation has been used to reduce inflammation quickly, and our experiments have shown that a single bout of high-frequency stimulation (30 minutes) can be effective as an anti-inflammatory treatment. 52 In addition, transcutaneous stimulation has been used to treat depression and headaches showing efficacy for even short-term applications using surface electrodes. 29 , 53 A study by He et al uses transcutaneous stimulation at the cervical or auricular vagus to effectively treat epilepsy.…”

Section: Potential Uses and Mechanisms Of Vnsmentioning

confidence: 99%

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A review of vagus nerve stimulation as a therapeutic intervention

Johnson

Wilson

2018

JIR

415

289

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In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications.

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Vagal nerve stimulation attenuates IL-6 and TNFα expression in respiratory regions of the developing rat brainstem

Cited by 22 publications

References 12 publications

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates

A review of vagus nerve stimulation as a therapeutic intervention

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