Brain Behav Immun. 2024 Apr 23:S0889-1591(24)00382-9. doi: 10.1016/j.bbi.2024.04.034. Online ahead of print.

ABSTRACT

The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines-including IL-6, IL-1β, and TNF-α-in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy’s beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy’s protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities.

PMID:38663772 | DOI:10.1016/j.bbi.2024.04.034

JAAPA. 2024 May 1;37(5):1-7. doi: 10.1097/01.JAA.0000000000000014. Epub 2024 Apr 25.

ABSTRACT

Migraine headache is a common and potentially debilitating disorder often treated by physician associates/assistants (PAs) and other providers. With the recent advances in new drugs and device technology for the treatment of migraine, the American Headache Society has released a consensus statement on both preventive and acute strategies for clinical practice. The US FDA has recently approved various types of medications and devices for the treatment and prevention of migraine attacks including several calcitonin gene-related peptide (CGRP) receptor inhibitors, a selective serotonin receptor agonist (SSRA), noninvasive vagus nerve stimulation (nVNS), external trigeminal nerve stimulation (e-TNS), and external concurrent occipital and trigeminal neurostimulation (eCOT-NS), among other pharmacologic and nonpharmacologic options. This article provides a review of migraine prevention and acute treatment protocol, highlighting new approaches to both.

PMID:38662902 | DOI:10.1097/01.JAA.0000000000000014

Seizure. 2024 Feb 19;117:298-304. doi: 10.1016/j.seizure.2024.02.011. Online ahead of print.

ABSTRACT

BACKGROUND: Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side.

OBJECTIVE: The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety.

METHODS: A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy.

RESULTS: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively).

CONCLUSION: Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients.

PMID:38615369 | DOI:10.1016/j.seizure.2024.02.011

Biochem Pharmacol. 2024 Apr 10:116201. doi: 10.1016/j.bcp.2024.116201. Online ahead of print.

ABSTRACT

Intestinal barrier dysfunction, leaky gut, is implicated in various diseases, including irritable bowel syndrome (IBS) and neurodegenerative conditions like Alzheimer’s disease. Our recent investigation revealed that basal forebrain cholinergic neurons (BFCNs), critical for cognitive function, receive signals from butyrate and orexin, playing a role in regulating intestinal barrier function through adenosine A2B signaling and the vagus. This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorpheniramine, an histamine H1 receptor antagonist, not ranitidine, an H2 receptor antagonist. The SKF91488-induced improvement in colonic hyperpermeability was blocked by vagotomy, intracisternal pirenzepine (suppressing BFCNs activity), or alloxazine (an adenosine A2B receptor antagonist). Additionally, intracisternal chlorpheniramine injection eliminated butyrate-induced improvement in colonic hyperpermeability. These findings suggest that brain histamine, acting via the histamine H1 receptor, regulates intestinal barrier function involving BFCNs, adenosine A2B signaling, and the vagus. Brain histamine appears to centrally regulate intestinal barrier function influenced by butyrate, differentiating its actions from peripheral histamine in conditions like IBS, where mast cell-derived histamine induces leaky gut. Brain histamine emerges as a potential pharmacological target for diseases associated with leaky gut, such as dementia and IBS.

PMID:38608783 | DOI:10.1016/j.bcp.2024.116201

J Transl Gastroenterol. 2023 Oct-Dec;1(2):94-100. doi: 10.14218/jtg.2023.00098. Epub 2023 Dec 25.

ABSTRACT

BACKGROUND AND OBJECTIVES: In this systematic review, we assessed the efficacy, potential mechanisms, and safety of two neuromodulation therapies in patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. The first therapy is vagus nerve stimulation (VNS) utilizing implantable or transcutaneous electrodes, and the second is sacral nerve stimulation (SNS) using implantable or percutaneous electrodes.

METHODS: We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed database was comprehensively searched, and studies were rigorously assessed for inclusion and exclusion criteria.

RESULTS: Our analysis encompassed five clinical studies, three on VNS and two on SNS. Most investigated studies demonstrated significant beneficial effects on IBD symptoms, including disease activity, severity of intestinal lesions, and intestinal pain. When evaluating the impact on key IBD pathophysiologies, both VNS and SNS exhibited trends toward reducing biomarkers of intestinal mucosal inflammation and mitigating sympathetic dominance. Importantly, none of the evaluated neuromodulation methods resulted in long-term adverse effects.

CONCLUSIONS: Cumulative evidence from the evaluated studies indicates that VNS and SNS therapies effectively alleviate IBD symptoms and may hold promise in addressing the underlying pathophysiologies of IBD, including intestinal mucosal inflammation and sympathetic dominance. Consequently, they represent valuable options for individualized IBD treatment.

PMID:38606364 | PMC:PMC11007757 | DOI:10.14218/jtg.2023.00098

Appl Psychophysiol Biofeedback. 2024 Apr 12. doi: 10.1007/s10484-024-09639-0. Online ahead of print.

ABSTRACT

Many studies have examined the effects of meditation practice focused on the normal breath on vagal tone with mixed results. Heart Rhythm Meditation (HRM) is a unique meditation form that engages in the deep slow full breath, and puts the focus of attention on the heart. This form of breathing likely stimulates the vagus nerve with greater intensity. The purpose of this study was (a) to examine how the practice of HRM affects vagal activity as measured by heart rate variability (HRV); and (b) to examine how it affects participants’ well-being. 74 participants signed consent agreeing to: (a) take a six-week course to learn the practice of HRM; (b) engage in a daily practice for 10 weeks; (c) have their heart rate variability read through ECG technology and to take two validated well-being instruments at the beginning and end of the 10 weeks; and (d) participate in a focus group interview examining their perceptions of how the practice affected their well-being. 48 participants completed the study. Quantitative findings show the effect of the practice of HRM approached significance for multiple measures of HRV and vagal tone. An increase in well-being scores for those who did the meditation more than 10-minutes per day did meet statistical significance. Qualitative data indicate: (a) the positive effects of HRM on stress and well-being; (b) the development of a more expanded sense of self; and (c) an increased awareness of the interconnection of the body-heart-emotions and HRM’s role in emotion regulation.

PMID:38605265 | DOI:10.1007/s10484-024-09639-0

BMJ Open. 2024 Apr 10;14(4):e082764. doi: 10.1136/bmjopen-2023-082764.

ABSTRACT

INTRODUCTION: Poststroke cognitive impairment is a common complication in stroke survivors, seriously affecting their quality of life. Therefore, it is crucial to improve cognitive function of patients who had a stroke. Transcranial direct current stimulation (tDCS) and transcutaneous auricular vagus nerve stimulation (taVNS) are non-invasive, safe treatments with great potential to improve cognitive function in poststroke patients. However, further improvements are needed in the effectiveness of a single non-invasive brain stimulation technique for cognitive rehabilitation. This study protocol aims to investigate the effect and neural mechanism of the combination of tDCS and taVNS on cognitive function in patients who had a stroke.

METHODS AND ANALYSIS: In this single-centre, prospective, parallel, randomised controlled trial, a total of 66 patients with poststroke cognitive impairment will be recruited and randomly assigned (1:1:1) to the tDCS group, the taVNS group and the combination of tDCS and taVNS group. Each group will receive 30 min of treatment daily, five times weekly for 3 weeks. Primary clinical outcome is the Montreal Cognitive Assessment. Secondary clinical outcomes include the Mini-Mental State Examination, Stroop Colour Word Test, Trail Marking Test, Symbol Digit Modalities Test and Modified Barthel Index. All clinical outcomes, functional MRI and diffusion tensor imaging will be measured at preintervention and postintervention.

ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of the First Affiliated Hospital of Yangtze University (approval no: KY202390). The results will be submitted for publication in peer-reviewed journals or at scientific conferences.

TRIAL REGISTRATION NUMBER: ChiCTR2300076632.

PMID:38604630 | DOI:10.1136/bmjopen-2023-082764

Int Immunopharmacol. 2024 Apr 10;132:112030. doi: 10.1016/j.intimp.2024.112030. Online ahead of print.

ABSTRACT

Mast cells (MCs) play a significant role in various diseases, and their activation and degranulation can trigger inflammatory responses and barrier damage. Several studies have indicated that vagus nerve stimulation (VNS) exerts ameliorates neurological injury, and regulates gut MC degranulation. However, there is limited research on the modulatory effect of VNS on MCs in both the gut and brain in brain ischemia-reperfusion (I/R) injury in this process. We aim to develop a minimally invasive, targeted and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs on the prognosis of acute ischemic stroke. We utilized middle cerebral artery occlusion/reperfusion (MCAO/r) to induce brain I/R injury. After the experiment, the motor function and neurofunctional impairments of the rats were detected, and the gastrointestinal function, blood-brain barrier (BBB) and intestinal barrier damage, and systemic and local inflammation were evaluated by Nissl, TTC staining, Evans blue, immunofluorescence staining, transmission electron microscopy, western blot assays, ELISA, and fecal 16S rRNA sequencing methods. Our research confirmed that our minimally invasive VNS method is a novel approach for stimulating the vagus nerve. VNS alleviated motor deficits and gastrointestinal dysfunction while also suppressing intestinal and neuroinflammation. Additionally, VNS ameliorated gut microbiota dysbiosis in rats. Furthermore, our analysis indicated that VNS reduces chymase secretion by modulating MCs degranulation and improves intestinal and BBB damage. Our results showed that VNS treatment can alleviate the damage of BBB and colonic barrier after cerebral I/R by modulating mast cell degranulation, and alleviates systemic inflammatory responses.

PMID:38603861 | DOI:10.1016/j.intimp.2024.112030

Psychophysiology. 2024 Apr 11:e14584. doi: 10.1111/psyp.14584. Online ahead of print.

ABSTRACT

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABA_Aergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

PMID:38602055 | DOI:10.1111/psyp.14584

Gland Surg. 2024 Mar 27;13(3):351-357. doi: 10.21037/gs-23-428. Epub 2024 Mar 20.

ABSTRACT

BACKGROUND: Skin electrodes have been reported to be a useful alternative recording method for intraoperative neuromonitoring (IONM) and show typical electromyography (EMG) waveforms while overcoming the shortcomings of the EMG endotracheal tube. However, the skin electrodes showed relatively lower evoked amplitudes than other recording methods. In this study, we analyzed normative EMG data using skin electrodes and factors that affect the evoked amplitude of thyroid IONM.

METHODS: In total, 167 patients [242 nerves at risk (NAR)] who underwent thyroidectomy under IONM with adhesive skin electrodes were analyzed. A pair of skin electrodes was attached to the lateral border of the lamina of the thyroid cartilage. Evoked EMG data, including mean amplitude and latency, obtained after stimulation of the recurrent laryngeal nerve (RLN) and vagus nerve (VN), were collected and analyzed.

RESULTS: The mean amplitudes of RLN and VN recorded via skin electrodes were 255.48±96.53 and 236.15±69.72 μV, respectively. The mean latency of the right and left RLN was 3.22±0.03 and 3.49±0.08 mS, respectively. The mean latency of the right and left VN was 5.37±0.80 and 7.57±0.10 mS, respectively. The mean amplitude was significantly lower in the obesity, male, and total thyroidectomy (TT) groups. As body mass index (BMI) and age increased, the amplitude of EMG tended to decrease significantly.

CONCLUSIONS: The evoked amplitude recorded with the skin electrodes was relatively low. A larger surgical extent, obesity, male sex, and age >55 years showed significantly lower evoked amplitudes.

PMID:38601295 | PMC:PMC11002475 | DOI:10.21037/gs-23-428