Clinical Vagus Nerve Stimulation Paradigms Induce Pronounced Brain and Body Hypothermia in Rats

2017 ◽  
Vol 27 (05) ◽  
pp. 1750016 ◽  
Author(s):  
Lars Emil Larsen ◽  
Wouter Van Lysebettens ◽  
Charlotte Germonpré ◽  
Sofie Carrette ◽  
Sofie Daelemans ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Diseases ◽  
Brain Temperature ◽  
Release Mechanism ◽  
Therapeutic Effects ◽  
Physiological Processes ◽  
Hypothermic Effect ◽  
Future Direction

Vagus nerve stimulation (VNS) is a widely used neuromodulation technique that is currently used or being investigated as therapy for a wide array of human diseases such as epilepsy, depression, Alzheimer’s disease, tinnitus, inflammatory diseases, pain, heart failure and many others. Here, we report a pronounced decrease in brain and core temperature during VNS in freely moving rats. Two hours of rapid cycle VNS (7s on/18s off) decreased brain temperature by around [Formula: see text]C, while standard cycle VNS (30[Formula: see text]s on/300[Formula: see text]s off) was associated with a decrease of around [Formula: see text]C. Rectal temperature similarly decreased by more than [Formula: see text]C during rapid cycle VNS. The hypothermic effect triggered by VNS was further associated with a vasodilation response in the tail, which reflects an active heat release mechanism. Despite previous evidence indicating an important role of the locus coeruleus-noradrenergic system in therapeutic effects of VNS, lesioning this system with the noradrenergic neurotoxin DSP-4 did not attenuate the hypothermic effect. Since body and brain temperature affect most physiological processes, this finding is of substantial importance for interpretation of several previously published VNS studies and for the future direction of research in the field.

scholarly journals Therapeutic effects of children with refractory epilepsy after vagus nerve stimulation in Taiwan

2020 ◽  
Vol 61 (6) ◽  
pp. 606-612
Author(s):  
Sung-Tse Li ◽  
Nan-Chang Chiu ◽  
Kun-Long Hung ◽  
Che-Sheng Ho ◽  
Yung-Ting Kuo ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Refractory Epilepsy ◽  
Therapeutic Effects

scholarly journals Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson’s Disease Model Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 789
Author(s):  
Ittetsu Kin ◽  
Tatsuya Sasaki ◽  
Takao Yasuhara ◽  
Masahiro Kameda ◽  
Takashi Agari ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Dopamine Neurons ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Stimulation Intensity ◽  
Anti Inflammatory

Background: The major surgical treatment for Parkinson’s disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. Methods: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). Results: VNS with 0.25–0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. Conclusions: VNS with 0.25–0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.

scholarly journals Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Conan Chen ◽  
Yixiang Mao ◽  
Maryam Falahpour ◽  
Kelly H. MacNiven ◽  
Gary Heit ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
High Frequency ◽  
Repeated Measures ◽  
Vagus Nerve Stimulation ◽  
Healthy Subjects ◽  
Therapeutic Effects ◽  
Sustained Effects

AbstractTranscutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF, a promising metric for the assessment of the sustained effects of taVNS. Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 min of either sub-threshold taVNS treatment or a sham control. taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical populations, and also supports the use of ASL measures of CBF for the assessment of the sustained effects of taVNS.

scholarly journals Vagus Nerve Stimulation: A Potential Adjunct Therapy for COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Eric Azabou ◽  
Guillaume Bao ◽  
Rania Bounab ◽  
Nicholas Heming ◽  
Djillali Annane
Keyword(s):  
Clinical Trials ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Diseases ◽  
Experimental Models ◽  
Research Strategies ◽  
Adjunct Therapy ◽  
Therapeutic Research ◽  
Effective Drugs

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through excessive end organ inflammation. Despite improved understanding of the pathophysiology, management, and the great efforts worldwide to produce effective drugs, death rates of COVID-19 patients remain unacceptably high, and effective treatment is unfortunately lacking. Pharmacological strategies aimed at modulating inflammation in COVID-19 are being evaluated worldwide. Several drug therapies targeting this excessive inflammation, such as tocilizumab, an interleukin (IL)-6 inhibitor, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, and intravenous immunoglobulin have been identified as potentially useful and reliable approaches to counteract the cytokine storm. However, little attention is currently paid for non-drug therapeutic strategies targeting inflammatory and immunological processes that may be useful for reducing COVID-19-induced complications and improving patient outcome. Vagus nerve stimulation attenuates inflammation both in experimental models and preliminary data in human. Modulating the activity of cholinergic anti-inflammatory pathways (CAPs) described by the group of KJ Tracey has indeed become an important target of therapeutic research strategies for inflammatory diseases and sepsis. Non-invasive transcutaneous vagal nerve stimulation (t-VNS), as a non-pharmacological adjuvant, may help reduce the burden of COVID-19 and deserve to be investigated. VNS as an adjunct therapy in COVID-19 patients should be investigated in clinical trials. Two clinical trials on this topic are currently underway (NCT04382391 and NCT04368156). The results of these trials will be informative, but additional larger studies are needed.

scholarly journals Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow

2021 ◽  
Author(s):  
Conan Chen ◽  
Yixiang Mao ◽  
Maryam Falahpour ◽  
Kelly H MacNiven ◽  
Gary Heit ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
High Frequency ◽  
Repeated Measures ◽  
Vagus Nerve Stimulation ◽  
Healthy Subjects ◽  
Therapeutic Effects ◽  
Brain Response

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). Objective/Hypothesis: The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF. Methods: Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 minutes of either sub-threshold taVNS treatment or a sham control. Results: taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Conclusions: Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical popluations to assess whether similar effects can be observed and are related to treatment outcomes.

scholarly journals Therapeutic Effects of Vagus Nerve Stimulation in Intractable Childhood Epilepsy: Experience for 12 Months after VNS Implantation

2008 ◽  
Vol 44 (1) ◽  
pp. 31
Author(s):  
Soo Min Oh ◽  
Eun Young Park ◽  
Ik Sun Choi ◽  
Young Kuk Cho ◽  
Young Ok Kim ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Therapeutic Effects ◽  
Childhood Epilepsy

scholarly journals Vagus Nerve Stimulation Induced Motor Map Plasticity Does Not Require Cortical Dopamine

2021 ◽  
Vol 15 ◽  
Author(s):  
Jackson Brougher ◽  
Camilo A. Sanchez ◽  
Umaymah S. Aziz ◽  
Kiree F. Gove ◽  
Catherine A. Thorn
Keyword(s):  
Vagus Nerve ◽  
Skill Acquisition ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Cortical Plasticity ◽  
Therapeutic Effects ◽  
Fiber Density ◽  
Motor Mapping ◽  
6 Hydroxydopamine ◽  
The Impact

Background: Vagus nerve stimulation (VNS) paired with motor rehabilitation is an emerging therapeutic strategy to enhance functional recovery after neural injuries such as stroke. Training-paired VNS drives significant neuroplasticity within the motor cortex (M1), which is thought to underlie the therapeutic effects of VNS. Though the mechanisms are not fully understood, VNS-induced cortical plasticity is known to depend on intact signaling from multiple neuromodulatory nuclei that innervate M1. Cortical dopamine (DA) plays a key role in mediating M1 synaptic plasticity and is critical for motor skill acquisition, but whether cortical DA contributes to VNS efficacy has not been tested.Objective: To determine the impact of cortical DA depletion on VNS-induced cortical plasticity.Methods: Rats were trained on a skilled reaching lever press task prior to implantation of VNS electrodes and 6-hydroxydopamine (6-OHDA) mediated DA depletion in M1. Rats then underwent training-paired VNS treatment, followed by cortical motor mapping and lesion validation.Results: In both intact and DA-depleted rats, VNS significantly increased the motor map representation of task-relevant proximal forelimb musculature and reduced task-irrelevant distal forelimb representations. VNS also significantly increased tyrosine hydroxylase (TH+) fiber density in intact M1, but this effect was not observed in lesioned hemispheres.Conclusion: Our results reveal that though VNS likely upregulates catecholaminergic signaling in intact motor cortices, DA itself is not required for VNS-induced plasticity to occur. As DA is known to critically support M1 plasticity during skill acquisition, our findings suggest that VNS may engage a unique set of neuromodulatory signaling pathways to promote neocortical plasticity.

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