Non-invasive vagus nerve stimulation in anti-inflammatory therapy: mechanistic insights and future perspectives

Front Neurosci. 2024 Nov 13;18:1490300. doi: 10.3389/fnins.2024.1490300. eCollection 2024.

ABSTRACT

Non-invasive vagus nerve stimulation (VNS) represents a transformative approach for managing a broad spectrum of inflammatory and autoimmune conditions, including rheumatoid arthritis and inflammatory bowel disease. This comprehensive review delineates the mechanisms underlying VNS, emphasizing the cholinergic anti-inflammatory pathway, and explores interactions within the neuro-immune and vagus-gut axes based on both clinical outcomes and pre-clinical models. Clinical applications have confirmed the efficacy of VNS in managing specific autoimmune diseases, such as rheumatoid arthritis, and chronic inflammatory conditions like inflammatory bowel disease, showcasing the variability in stimulation parameters and patient responses. Concurrently, pre-clinical studies have provided insights into the potential of VNS in modulating cardiovascular and broader inflammatory responses, paving the way for its translational application in clinical settings. Innovations in non-invasive VNS technology and precision neuromodulation are enhancing its therapeutic potential, making it a viable option for patients who are unresponsive to conventional treatments. Nonetheless, the widespread adoption of this promising therapy is impeded by regulatory challenges, patient compliance issues, and the need for extensive studies on long-term efficacy and safety. Future research directions will focus on refining VNS technology, optimizing treatment parameters, and exploring synergistic effects with other therapeutic modalities, which could revolutionize the management of chronic inflammatory and autoimmune disorders.

PMID:39605787 | PMC:PMC11599236 | DOI:10.3389/fnins.2024.1490300

Cranial motor neuron input specificity refined by activity

Trends Neurosci. 2024 Nov 27:S0166-2236(24)00223-6. doi: 10.1016/j.tins.2024.11.001. Online ahead of print.

ABSTRACT

A recent study by Kaneko and colleagues provides evidence that developing cranial motor neurons in larval zebrafish refine their input specificity over time, using an activity-dependent mechanism that may depend, in part, on adaptive dendrite extension. These findings illuminate the mechanism by which spatially overlapping motor pools are recruited into distinct motor circuits.

PMID:39609183 | DOI:10.1016/j.tins.2024.11.001

The Nuchal Cord Conundrum: Understanding and Addressing Umbilical Entanglement in the Third Trimester of Pregnancy

J Clin Med. 2024 Nov 14;13(22):6836. doi: 10.3390/jcm13226836.

ABSTRACT

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy.

PMID:39598007 | PMC:PMC11594921 | DOI:10.3390/jcm13226836

Young rat microbiota extracts strongly inhibit fibrillation of α-synuclein and protect neuroblastoma cells and zebrafish against α-synuclein toxicity

Mol Cells. 2024 Nov 25:100161. doi: 10.1016/j.mocell.2024.100161. Online ahead of print.

ABSTRACT

The clinical manifestations of Parkinson’s Disease (PD) are driven by aggregation of α-Synuclein (α-Syn) in the brain. However, there is increasing evidence that PD may be initiated in the gut and thence spread to the brain, e.g. via the vagus nerve. Many studies link PD to changes in the gut microbiome, and bacterial amyloid has been shown to stimulate α-syn aggregation. Yet we are not aware of any studies reporting on a direct connection between microbiome components and α-Syn aggregation. Here we report that soluble extract from the gut microbiome of the rats, particularly young rats transgenic for PD, show a remarkably strong ability to inhibit in vitro α-Syn aggregation and keep it natively unfolded and monomeric. The active component(s) are heat-labile molecule(s) of around 30-100 kDa size which are neither nucleic acid nor lipid. Proteomic analysis identified several proteins whose concentrations in different rat samples correlated with the samples’ anti-inhibitory activity, while a subsequent pulldown assay linked the protein chaperone DnaK with the inhibitory activity of young rat’s microbiome, confirmed in subsequent in vitro assays. Remarkably, the microbiome extracts also protected neuroblastoma SH-SY5Y cells and zebrafish embryos against α-Syn toxicity. Our study sheds new light on the gut microbiome as a potential source of protection against PD and opens up for new microbiome-based therapeutic strategies.

PMID:39603509 | DOI:10.1016/j.mocell.2024.100161

Effect of chronic exogenous oxytocin administration on exercise performance and cardiovagal control in hypobaric hypoxia in rats

Biol Res. 2024 Nov 23;57(1):88. doi: 10.1186/s40659-024-00573-3.

ABSTRACT

BACKGROUND: Outstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats.

RESULTS: A vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO2: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups.

CONCLUSION: The findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH.

PMID:39578887 | DOI:10.1186/s40659-024-00573-3

Effect of remimazolam besylate versus propofol on haemodynamic profiles in patients undergoing thyroid surgery with recurrent laryngeal nerve monitoring: a protocol for a randomised controlled trial

BMJ Open. 2024 Nov 21;14(11):e089650. doi: 10.1136/bmjopen-2024-089650.

ABSTRACT

INTRODUCTION: Thyroid surgery with intraoperative nerve monitoring under total intravenous anaesthesia often requires deeper sedation due to limitations or lack of neuromuscular blocking agents, usually resulting in haemodynamic instability. Remimazolam, a newly developed sedative, is being studied for its effect on the haemodynamic profile of patients undergoing this procedure and compared with propofol.

METHODS AND ANALYSIS: This will be a single-centre, single-blind, randomised, controlled trial in American Society of Anesthesiologists I-III patients between the ages of 18 and 65 who require recurrent laryngeal nerve monitoring for thyroid surgery. Patients will be randomised 1:1 to either remimazolam besylate or propofol, with 142 cases in each group according to a randomised, computer-generated cohort. The primary outcome is the occurrence of hypotension from induction of anaesthesia to full recovery. Secondary outcomes include the administration of vasoactive agents, the number of hypotension or hypertension episodes, the cumulative duration of hypotension or hypertension, the dose of intraoperative rescue sedation and analgesia, the time to extubation and awakening and the incidence of adverse events.

ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Medical Ethics Committee of the Affiliated Cancer Hospital and Institute of Guangzhou Medical University (2023-2024). The study protocol was modified according to the reviewers’ comments, and the revised version was approved by the Ethics Committee (2024 Research Ethics Amendment No. 3). On completion of the study, we will commit to ensuring that the results are made available to the public, regardless of the outcome. This will include either publication in an appropriate journal or oral presentation at academic conferences.

TRIAL REGISTRATION NUMBER: ChiCTR2300076583.

PMID:39578027 | DOI:10.1136/bmjopen-2024-089650

Research trends of acupressure from 2004 to 2024: A bibliometric and visualization analysis

Heliyon. 2024 Sep 29;10(21):e38675. doi: 10.1016/j.heliyon.2024.e38675. eCollection 2024 Nov 15.

ABSTRACT

BACKGROUND: Acupressure has proven efficacy in symptoms management, making it valuable in clinical practice and patient care. Given the rising number of increasing publications on acupressure, we aimed to analyze the literature from the past 20 years and provided current trends and hotspot for future research directions.

METHODS: Publications on acupressure from January 1, 2004 through May 1, 2024 were retrieved from the Web of Science database. The extracted records underwent thorough analysis based on publication year, research area, journal, countries/regions, organization, authors, and keywords. The bibliometric analysis was conducted using Citespace and Microsoft Excel software.

RESULTS: Of the 1,929 screened records, 770 publications were identified. The annual number of acupressure has gradually increased, with the 45 % of the total publication occurring from 2020 to 2024. Among countries and institutions, China (252 articles) and Hong Kong Polytechnic University (41 articles) have the highest number of publications. Notably, USA and Hong Kong Polytechnic University exhibits the highest centrality score in cooperative network among countries/regions and institutions. Chao Hsing Yeh from the Cizik School of Nursing, University of Texas Health Science Center, was the most prolific author with 22 papers. Evidence-Based Comple Alt, with 53 articles, is the journal with the most publications. According to the keyword, timeline diagram and prominence mapping analysis, we believe that “insomnia”, “labor”, “waist circumference”, “reliability” and “vagus nerve stimulation” related clusters may be new hotspots in the field of acupressure.

CONCLUSION: This study presents the research trajectory of acupressure over the past 20 years, providing a foundation for future research and highlighting the significant contributions of nursing researchers. By analyzing research trends and hotsport, nursing professionals can integrate acupressure more effectively into holistic patient care, improving quality of life, and contributing to traditional Chinese medicine.

PMID:39568827 | PMC:PMC11577180 | DOI:10.1016/j.heliyon.2024.e38675

The emerging roles of neuroactive components produced by gut microbiota

Mol Biol Rep. 2024 Nov 21;52(1):1. doi: 10.1007/s11033-024-10097-4.

ABSTRACT

BACKGROUND: As a multifunctional ecosystem, the human digestive system contains a complex network of microorganisms, collectively known as gut microbiota. This consortium composed of more than 1013 microorganisms and Firmicutes and Bacteroidetes are the dominant microbes. Gut microbiota is increasingly recognized for its critical role in physiological processes beyond digestion. Gut microbiota participates in a symbiotic relationship with the host and takes advantage of intestinal nutrients and mutually participates in the digestion of complex carbohydrates and maintaining intestinal functions.

METHOD AND RESULT: We reviewed the neuroactive components produced by gut microbiota. Interestingly, microbiota plays a crucial role in regulating the activity of the intestinal lymphatic system, regulation of the intestinal epithelial barrier, and maintaining the tolerance to food immunostimulating molecules. The gut-brain axis is a two-way communication pathway that links the gut microbiota to the central nervous system (CNS) and importantly is involved in neurodevelopment, cognition, emotion and synaptic transmissions. The connections between gut microbiota and CNS are via endocrine system, immune system and vagus nerve.

CONCLUSION: The gut microbiota produces common neurotransmitters and neuromodulators of the nervous system. These compounds play a role in neuronal functions, immune system regulation, gastrointestinal homeostasis, permeability of the blood brain barrier and other physiological processes. This review investigates the essential aspects of the neurotransmitters and neuromodulators produced by gut microbiota and their implications in health and disease.

PMID:39570444 | DOI:10.1007/s11033-024-10097-4

Safety profile of abdominal magnetic resonance imaging (MRI) performed for renal disease surveillance in tuberous sclerosis complex patients with vagus nerve stimulation: Safety of MRI for TSC Patients with VNS

Seizure. 2024 Nov 8;123:148-151. doi: 10.1016/j.seizure.2024.11.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Individuals with tuberous sclerosis complex (TSC) often present with refractory epilepsy and may be undergoing treatment with vagus nerve stimulation (VNS) to control seizures. Surveillance magnetic resonance imaging (MRI) is necessary to monitor for the renal angiomyolipomas associated with TSC; however, MRI of the abdomen is not approved for patients withVNS therapy. We have many TSC patients with refractory epilelpsy who benefitted from VNS therapy, so we developed an MRI protocol that allows MRI of the abdomen to be performed in these patients to permit safe imaging of their kidneys. Here we report our results using this protocol.

METHODS: We performed a retrospective review for all TSC patients seen from 01/01/1997 to 10/01/2022 at a single center to determine VNS implantation status. Patients with VNS implants and abdomen imaging performed according to the protocol for kidney surveillance were included.

RESULTS: Sixteen patients with 48 total MRIs of the abdomen were found: 34 (71 %) scans were conducted under sedation and 14 (29 %) without sedation. None of the patients reported any adverse effects (pain or discomfort). No instances of VNS dysfunction were noted when re-interrogating the device immediately after completion of the imaging studies or at later neurology follow-up appointments. All MRI scans were of good quality for interpretation.

CONCLUSION: Abdominal MRIs performed in typical VNS exclusion zones were not associated with adverse events or VNS dysfunction. We believe this protocol is safe and permits the best method for monitoring renal disease in TSC patients with VNS.

PMID:39571475 | DOI:10.1016/j.seizure.2024.11.005

Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation

Commun Biol. 2024 Nov 19;7(1):1536. doi: 10.1038/s42003-024-07222-1.

ABSTRACT

Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.

PMID:39562711 | PMC:PMC11576867 | DOI:10.1038/s42003-024-07222-1