scholarly journals Vagus Nerve Stimulation Promotes Epithelial Proliferation and Controls Colon Monocyte Infiltration During DSS-Induced Colitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Elisa Meroni ◽  
Nathalie Stakenborg ◽  
Pedro J. Gomez-Pinilla ◽  
Michelle Stakenborg ◽  
Javier Aguilera-Lizarraga ◽  
...  

Background: We previously showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vagotomized mice. Here, we evaluated whether vagus nerve stimulation (VNS) is able to reduce the severity of DSS colitis and aimed to unravel the mechanism involved.Methods: Colitis was induced in wild type mice by 2.5% DSS administration in drinking water for 5 days. VNS (5 Hz, 1 ms, 1 mA) was applied 1 day prior to and after 4 days of DSS administration to evaluate changes in epithelial integrity and inflammatory response, respectively. Epithelial integrity was assessed using TUNEL and Ki67 staining. Monocytes, immature and mature macrophages were sorted from colonic samples and gene expression levels of pro-inflammatory cytokines were studied.Results: VNS applied prior to DSS administration (i.e., prophylactic VNS) reduced disease activity index (VNS 0.8 ± 0.6 vs. sham 2.8 ± 0.7, p < 0.001, n = 5) and tended to improve histology score. Prophylactic VNS significantly increased epithelial cell proliferation and diminished apoptosis compared to sham stimulation. VNS applied at day 4 during DSS administration (i.e., therapeutic VNS) decreased the influx of monocytes, monocyte-derived macrophages and neutrophils, and significantly reduced pro-inflammatory cytokine expression (i.e., Tnfα and Cxcl1) in immature macrophages compared to sham stimulation.Conclusions: A single period of VNS applied prior to DSS exposure reduced DSS-induced colitis by an improvement in epithelial integrity. On the other hand, VNS applied during the inflammatory phase of DSS colitis reduced cytokine expression in immature macrophages. Our data further underscores the potential of VNS as novel therapeutic approach for inflammatory bowel diseases.

2020 ◽  
Vol 3 (4) ◽  
pp. 51-62
Author(s):  
Zain Ul Abideen Asad ◽  
Adam Przebinda ◽  
Amna Mohyud Din Chaudhary ◽  
Samid Farooqui ◽  
Houssein Youness ◽  
...  

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. The infection triggers a host response with an early hyperinflammatory and subsequent anti-inflammatory phase, both regulated by homeostatic mechanisms. A breakdown of these regulatory mechanisms can result in an exaggerated immune response which leads to complications. The vagus nerve plays a central role in regulating inflammation and the balance between the sympathetic and parasympathetic arms of the autonomic nervous system through the “cholinergic anti-inflammatory pathway”. Several experimental models support the notion that external stimulation of the vagus nerve can modulate inflammation and restore the sympatho-vagal balance which may translate to improved outcomes in sepsis. Here, we review the pathophysiologic basis and evidence behind vagus nerve stimulation in sepsis.


2018 ◽  
Author(s):  
Bart Verkuil ◽  
Andreas Michael Burger

People suffering from chronic worries pay excessive attention to emotional information. In this study we examined whether a reduced ability to inhibit attention from fearful faces (i.e. inhibition of return; IOR) can be attributed to the low vagus nerve activity observed in high worriers. Our pre-registered hypothesis was that transcutaneous auricular vagus nerve stimulation (tVNS) would enhance IOR to fearful faces. Ninety-four students who scored above a pre-determined cut-off on the Penn State Worry Questionnaire were randomly allocated to receive either tVNS (n = 45) or sham stimulation of the earlobe (n = 49). Meanwhile, to assess IOR, they performed an emotional exogenous cueing task wherein neutral and fearful faces predicted the target location at chance level. Resting levels of HRV were also collected before stimulation onset. Results showed that levels of trait worry were associated with reduced IOR, but resting levels of HRV were not. Critically, tVNS did not affect performance on the exogenous cueing task when compared to sham stimulation. These findings did not confirm the hypothesized causal role of vagus nerve activity in maintaining disrupted IOR for emotional information. They also provide evidence that high levels of worry are associated with generally reduced IOR. This points to a clear need to understand the neurobiological basis of inhibitory problems in worriers.


2020 ◽  
Author(s):  
Omer Sharon ◽  
Firas Fahoum ◽  
Yuval Nir

AbstractVagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS), which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent that tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.Significance statementCurrent non-invasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating-current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4s) tVNS pulses in naïve healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus-noradrenaline signaling, and support the notion that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying the means by which endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.


2019 ◽  
Vol 28 (4) ◽  
pp. 1381-1387
Author(s):  
Ying Yuan ◽  
Jie Wang ◽  
Dongyu Wu ◽  
Dahua Zhang ◽  
Weiqun Song

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


2021 ◽  
Vol 3 (1) ◽  
pp. e14-e15
Author(s):  
Mark C Genovese ◽  
Yaakov A Levine ◽  
David Chernoff

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 ◽  
...  

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