Clin Auton Res. 2024 Dec 14. doi: 10.1007/s10286-024-01101-9. Online ahead of print.

NO ABSTRACT

PMID:39673646 | DOI:10.1007/s10286-024-01101-9

Biomed Pharmacother. 2024 Dec 12;182:117748. doi: 10.1016/j.biopha.2024.117748. Online ahead of print.

ABSTRACT

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) widely used for depression, but its potential effects on gut microbiota regulation and vagus nerve-mediated serotonin receptor expression have not been well studied. We investigated changes in the gut microbiome regulated by fluoxetine and vagus nerve-mediated expression of several serotonin (5-HT) receptor types associated with anxiety and depression. Oral administration of fluoxetine alleviated lipopolysaccharide (LPS)-induced depressive and anxiety behaviors, increased 5-HT1A, 2 C, and melanocortin 4 (MC4) receptor expression, and the composition of Lactobacillus in mice’s gut microbiome. In contrast, in the vagotomized group, fluoxetine did not modulate behaviors and receptor expression. Increased Lactobacillus composition was found to correlate significantly with behavioral test results. The importance of Lactobacillus growth to the efficacy of fluoxetine was confirmed by the effectiveness of fluoxetine, which was reduced by co-administering antibiotics. To determine the additional impact of the gut microbiome, we isolated Limosilactobacillus reuteri and Ligilactobacillus murinus, which were increased in the fluoxetine-treated group and administrated. The results showed that administration of each strain improved anxious or depressive behavior, as did fluoxetine, and vagotomy eliminated these effects. These results suggest that fluoxetine administration increases the proportion of Lactobacillus in the gut, which modulates 5-HT1A, 2 C, and MC4 receptor expression through the enteric nervous system and improves depression.

PMID:39671722 | DOI:10.1016/j.biopha.2024.117748

Int J Yoga Therap. 2024 Dec 1;34(2024):Article 18. doi: 10.17761/2024-D-24-00020.

ABSTRACT

Changes in breathing during pranayama (yoga breathwork) are usually inferred from practice guidelines in traditional texts or contemporary writings. These changes point to understanding the effects of pranayama and indicate applications of pranayama in health. Previously, a pilot study on a single participant suggested that each pranayama changes breathing uniquely. To extend this research in the present study, 23 yoga practitioners (mean age 28.1 ± 3.8; 12 men, 11 women) who were able to practice the pranayama consistently were each studied in a 48-minute session with five pranayama practices-(1) alternate-nostril yoga breathing, (2) bellows yoga breathing, (3) bumblebee yoga breathing, (4) high-frequency yoga breathing, and (5) hissing yoga breathing-as well as (6) breath awareness for 3 minutes each. From strain gauge-recorded respiratory movements, the breath frequency, depth/amplitude of breathing, and inspiration:expiration were obtained. Compared to the baseline, breath rate increased during high-frequency breathing (373.3%) and decreased during bumblebee breathing (75.3%), hissing breathing (63.0%), and alternate-nostril breathing (55.3 %). The depth of breathing increased in alternate-nostril breathing (141.0%), bellows breathing (136.0%), bumblebee breathing (307%), high-frequency breathing (275.0%), and hissing breathing (95.0%). The inspiration:expiration increased in high-frequency breathing (177.0%) and decreased in bumblebee breathing (74.3%) and alternate-nostril breathing (39.0%). There were no changes during breath awareness. The changes in breathing (although limited by the small sample size) support previous reports of high-frequency breathing as being activating while enhancing attention, and of bumblebee and alternate-nostril breathing (hissing and bellows breathing to a lesser extent) as calming, with increased vagus nerve activity.

PMID:39668415 | DOI:10.17761/2024-D-24-00020

Neural Regen Res. 2024 Dec 7. doi: 10.4103/NRR.NRR-D-24-00945. Online ahead of print.

ABSTRACT

Stroke remains a leading cause of long-term disability worldwide. There is an unmet need for neuromodulatory therapies that can mitigate against neurovascular injury and potentially promote neurological recovery. Transcutaneous vagus nerve stimulation has been demonstrated to show potential therapeutic effects in both acute and chronic stroke. However, previously published research has only investigated a narrow range of stimulation settings and indications. In this review, we detail the ongoing studies of transcutaneous vagus nerve stimulation in stroke through systematic searches of registered clinical trials. We summarize the upcoming clinical trials of transcutaneous vagus nerve stimulation in stroke, highlighting their indications, parameter settings, scope, and limitations. We further explore the challenges and barriers associated with the implementation of transcutaneous vagus nerve stimulation in acute stroke and stroke rehabilitation, focusing on critical aspects such as stimulation settings, target groups, biomarkers, and integration with rehabilitation interventions.

PMID:39665799 | DOI:10.4103/NRR.NRR-D-24-00945

Clin Auton Res. 2024 Dec 12. doi: 10.1007/s10286-024-01095-4. Online ahead of print.

NO ABSTRACT

PMID:39668329 | DOI:10.1007/s10286-024-01095-4

Neural Regen Res. 2024 Dec 7. doi: 10.4103/NRR.NRR-D-24-00836. Online ahead of print.

ABSTRACT

Neuromodulation techniques effectively intervene in cognitive function, holding considerable scientific and practical value in fields such as aerospace, medicine, life sciences, and brain research. These techniques utilize electrical stimulation to directly or indirectly target specific brain regions, modulating neural activity and influencing broader brain networks, thereby regulating cognitive function. Regulating cognitive function involves an understanding of aspects such as perception, learning and memory, attention, spatial cognition, and physical function. To enhance the application of cognitive regulation in the general population, this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions. This review covers various neuromodulation techniques for cognitive intervention, including deep brain stimulation, vagus nerve stimulation, and invasive methods using microelectrode arrays. The non-invasive techniques discussed include transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcutaneous electrical acupoint stimulation, and time interference stimulation for activating deep targets. Invasive stimulation methods, which are ideal for studying the pathogenesis of neurological diseases, tend to cause greater trauma and have been less researched in the context of cognitive function regulation. Non-invasive methods, particularly newer transcranial stimulation techniques, are gentler and more appropriate for regulating cognitive functions in the general population. These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets. This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology. It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation. Additionally, researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.

PMID:39665818 | DOI:10.4103/NRR.NRR-D-24-00836

Theranostics. 2024 Oct 28;14(19):7383-7404. doi: 10.7150/thno.101680. eCollection 2024.

ABSTRACT

Rationale: The vagus nerve, which connects the brain and gastrointestinal tract, helps to maintain immune balance in the intestines. Gut-specific integrins, on the other hand, help to keep immune cells in the intestines. Since immune cells from outside the intestines can significantly affect the outcome of strokes, we investigated how immune cells from the intestines affect the immune response in the brain during intracerebral hemorrhage (ICH). Methods: We aimed to examine the impact of vagal innervation on intestinal immunocyte trafficking and its influence on ICH outcomes using Kikume Green-Red (KikGR) and wildtype (WT) mice, with or without prior subdiaphragmatic vagotomy (SDV). Furthermore, we sought to elucidate the regulatory effects of vagal innervation on intestinal immunocyte trafficking by activating α7 nicotinic acetylcholine receptors (α7nAChR) in WT mice that underwent ICH after SDV. Additionally, we explored the potential intermediary role of gut-selective integrins in cholinergic transmitters-mediated intestinal immunocyte trafficking. Our methodology encompassed in vivo fluorescence imaging, flow cytometry, Western blotting, immunofluorescence staining, histopathology, and behavioral assessments to evaluate the outcomes. Results: Our findings reveal that during the acute phase of ICH, intestinal immunocytes migrated to various anatomical locations, including the circulation, hemorrhagic brain, meninges, and deep cervical lymph nodes. Pertinently, SDV resulted in diminished expression of α4β7 and αEβ7 integrins on immunocytes, leading to heightened intestinal immunocyte trafficking and exacerbated ICH outcomes. Conversely, the administration of α7nAChR agonists countered the adverse effects of vagotomy on α4β7 and αEβ7 integrin expression, thereby constraining the migration of immune cells from the intestines after ICH. The implication of α4β7 and αEβ7 integrins in this setting was supported by the ineffective influence of α7nAChR agonists on the trafficking of intestinal immunocytes enhanced by administering beta-7 integrin antagonists, such as etrolizumab. It was further supported by the exacerbated ICH outcomes by administering beta-7 integrin antagonists like etrolizumab alone. Conclusion: The identification of vagus nerve-mediated modulation of α4β7 and αEβ7 integrin expression in the trafficking of immune cells within the intestinal tract holds significant implications. This discovery presents new opportunities for developing therapeutic interventions for ICH and stimulates further investigation in this area.

PMID:39659582 | PMC:PMC11626938 | DOI:10.7150/thno.101680

Cell Rep. 2024 Dec 9;43(12):115045. doi: 10.1016/j.celrep.2024.115045. Online ahead of print.

ABSTRACT

Nociceptor neurons play a crucial role in maintaining the body’s homeostasis by detecting and responding to potential environmental dangers. However, this function can be detrimental during allergic reactions, as vagal nociceptors contribute to immune cell infiltration, bronchial hypersensitivity, and mucus imbalance in addition to causing pain and coughing. Despite this, the specific mechanisms by which nociceptors acquire pro-inflammatory characteristics during allergic reactions are not yet fully understood. In this study, we investigate the changes in the molecular profile of airway nociceptor neurons during allergic airway inflammation and identify the signals driving such reprogramming. Using retrograde tracing and lineage reporting, we identify a specific class of inflammatory vagal nociceptor neurons that exclusively innervate the airways. In the ovalbumin mouse model of allergic airway inflammation, these neurons undergo significant reprogramming characterized by the upregulation of the neuropeptide Y (NPY) receptor Npy1r. A screening of cytokines and neurotrophins reveals that interleukin 1β (IL-1β), IL-13, and brain-derived neurotrophic factor (BDNF) drive part of this reprogramming. IL-13 triggers Npy1r overexpression in nociceptors via the JAK/STAT6 pathway. In parallel, NPY is released into the bronchoalveolar fluid of asthmatic mice, which limits the excitability of nociceptor neurons. Single-cell RNA sequencing of lung immune cells reveals that a cell-specific knockout of NPY1R in nociceptor neurons in asthmatic mice altered T cell infiltration. Opposite findings are observed in asthmatic mice in which nociceptor neurons are chemically ablated. In summary, allergic airway inflammation reprograms airway nociceptor neurons to acquire a pro-inflammatory phenotype, while a compensatory mechanism involving NPY1R limits the activity of nociceptor neurons.

PMID:39661516 | DOI:10.1016/j.celrep.2024.115045

eNeurologicalSci. 2024 Nov 13;37:100535. doi: 10.1016/j.ensci.2024.100535. eCollection 2024 Dec.

ABSTRACT

•The trigeminal autonomic cephalalgias are a severe disabling form of primary headache disorders characterized by severe unilateral pain commonly associated with ipsilateral cranial autonomic features as well as a sense of restlessness or agitation, of which the most common is cluster headache.•Different forms of trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania (PH), hemicrania continua (HC), short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) and are differentiated based on their duration and frequency•Triptans, such as sumatriptan by injection, high flow 100 % oxygen by face mask, or non-invasive vagus nerve stimulation, are mainstay acute treatments of attacks of cluster headache.•Interim preventive treatments to reduce attack frequency include a short course of high dose oral corticosteroids, local anesthetic/corticosteroid injection around the homolateral (to pain) greater occipital nerve or the CGRP monoclonal antibody galcanezumab.•Verapamil is considered the mainstay medium to long-term preventive with additional options being lithium, melatonin, topiramate, or non-invasive and invasive neuromodulation.

PMID:39654689 | PMC:PMC11626532 | DOI:10.1016/j.ensci.2024.100535

Curr Opin Biomed Eng. 2024 Dec;32:100557. doi: 10.1016/j.cobme.2024.100557. Epub 2024 Aug 24.

ABSTRACT

Computational models of electrical stimulation, block and recording of autonomic nerves enable analysis of mechanisms of action underlying neural responses and design of optimized stimulation parameters. We reviewed advances in computational modeling of autonomic nerve stimulation, block, and recording over the past five years, with a focus on vagus nerve stimulation, including both implanted and less invasive approaches. Few models achieved quantitative validation, but integrated computational pipelines increase the reproducibility, reusability, and accessibility of computational modeling. Model-based optimization enabled design of electrode geometries and stimulation parameters for selective activation (across fiber locations or types). Growing efforts link models of neural activity to downstream physiological responses to represent more directly the therapeutic effects and side effects of stimulation. Thus, computational modeling is an increasingly important tool for analysis and design of bioelectronic therapies.

PMID:39650310 | PMC:PMC11619812 | DOI:10.1016/j.cobme.2024.100557