Search Results (18)

Heart failure, a significant global health burden, is divided into heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), characterized by systolic dysfunction and diastolic stiffness, respectively. While HFrEF benefits from pharmacological and device-based therapies, HFpEF lacks effective treatments, with both conditions leading to high rehospitalization rates and reduced quality of life, especially in older adults with comorbidities. This review explores the role of artificial intelligence (AI) in advancing autonomic neuromodulation for heart failure management. AI enhances patient selection, optimizes stimulation strategies, and enables adaptive, closed-loop systems. In HFrEF, vagus nerve stimulation and baroreflex activation therapy improve functional status and biomarkers, while AI-driven models adjust stimulation dynamically based on physiological feedback. In HFpEF, AI aids in deep phenotyping to identify responsive subgroups for neuromodulatory interventions. Clinical tools support remote monitoring, risk assessment, and symptom detection. However, challenges like data integration, ethical oversight, and clinical adoption limit real-world application. Algorithm transparency, bias minimization, and equitable access are critical for success. Interdisciplinary collaboration and ethical innovation are essential to develop personalized, data-driven, patient-centered heart failure treatment strategies through AI-guided neuromodulation. Full article

This review provides an overview of the most significant developments in gout pathophysiology research published in 2024. Thirteen studies were selected based on originality, scientific rigor, and potential clinical impact and grouped into four major categories: inflammation and pain mechanisms (LRRC8 anion channels, CXCL5-CXCR2 axis, CD38 and NAD⁺ metabolism, PLK1 and NLRP3 inflammasome localization, and IFN1 suppression), biomarkers and proteomics (scRNA-seq reveals monocyte and T-cell flare signatures, and Olink serum profiling reveals a proinflammatory signature in hyperuricemia and also identifies TNFSF14 as a novel flare biomarker, while a multi-omics integrative study implicates TRIM46 as a key causal gene), gut virome, and novel therapies (vagus nerve stimulation, biomimetic nanosystem, and restoration of Urate Oxidase (Uox) function). The studies selected focused primarily on work on subjects other than on hyperuricemia. The findings collectively expand our understanding of gout’s complex pathophysiology and highlight potential strategies for diagnosis, management, and innovative treatments. Full article

Background/Objectives: Low-frequency alternating current (LFAC) has been shown to induce nerve conduction block (LFACb). However, the effects of LFAC on conduction delay prior to block remain unclear. This study investigates the impact of LFACb on conduction velocity and blocking thresholds in myelinated and unmyelinated fibers using experimental and computational models. Methods: Four models were employed to analyze LFACb effects: (1) in-vivo experiments in earthworms examined conduction delays across nerve bundles with distinct conduction velocities; (2) ex-vivo experiments in canine vagus nerves assessed the upstream and downstream effects of LFAC waveforms ranging from 50 mHz to 500 mHz; (3) in-silico simulations using the Horn, Yoshida, and Schild (HYS) model for unmyelinated fibers explored size-dependent conduction delays and blocking thresholds; and (4) in-silico simulations using the McIntyre, Richardson, and Grill (MRG) model extended to 504 Nodes of Ranvier characterized myelination effects, localized nodal interactions, and diameter-dependent thresholds. Results: LFAC-induced conduction delays were independent of LFAC frequency but strongly influenced by fiber diameter and conduction velocity. Larger fibers exhibited lower block thresholds and shorter delays before block onset. In contrast, smaller fibers demonstrated prolonged subthreshold conduction delays before achieving full block. Conclusions: These findings suggest that LFACb could serve as a neuromodulation tool for selectively blocking larger fibers while preserving smaller fiber function. This has potential applications in functional electrical stimulation (FES) and temporary, non-destructive nerve blocks for clinical and research applications. Full article

Background and Objectives: This study aimed to discuss positional changes in the sternocleidomastoid (SCM) muscle and vagus nerve with head position, their effect on the surgical path, positional variations, the selection of an appropriate position for surgery, their effects on the surgical procedure, and complications by using peroperative ultrasonography. Materials and Methods: Vagal nerve stimulation surgery patients over the age of 18 years were included. Peroperative ultrasonography images were scanned, and changes in head position and anatomical and positional variations in the SCM muscle and vagus nerve at the surgical incision level were examined. Results: SCM localization was most frequently observed in the lateral aspect of the carotid sheath (n:16) in neutral position, while it was mostly observed in the medial aspect of the carotid sheath (n:16) at a 15 degree rotation. The vagus nerve was mostly observed between the jugular vein and carotid artery in neutral position (n:21), and it was observed at the same position at a 15 degree rotation (n:17). The positional change of the SCM muscle with head position was found to be statistically significant (p < 0.001), while the positional change of the vagus nerve was not (p:0.198). Conclusions: The SCM muscle closes the surgical path with head rotation by either deviating over the carotid sheath or increasing its deviation. In addition to its anatomical variations, the vagus nerve shows different positional changes with head rotation. Deciding on the head position in vagal nerve stimulation surgery, using peroperative ultrasonography rather than a routine position, may be effective in reducing surgical time and possible complications. Full article

Background: Transient receptor potential vanilloid subtype 4 (TRPV4) is a Ca²⁺-permeable non-selective cation channel that is involved in the development of cough hypersensitivity. Purinergic 2 receptors (P2X) belong to a class of adenosine triphosphate (ATP)-gated non-selective cation channels that also play an important role in cough hypersensitivity. Nevertheless, little is known about the interaction between them for cough hypersensitivity. The present study was designed to clarify the roles of TRPV4 and ATP-P2X receptors in cough hypersensitivity, and to explore the possible involvement of ATP-P2X receptors in the development of cough hypersensitivity mediated by TRPV4. Design and Method: This study aims to establish a guinea pig model of citric acid-induced enhanced cough to confirm the effects of the TRPV4-mediated purinergic signaling pathway on cough sensitivity by testing the number of coughs, the release of ATP, and the expressions of P2X and TRPV4 receptors in the tracheal carina and vagal ganglion; recording the activity of cellular currents with the whole-cell patch clamp technique; and detecting changes in intracellular calcium flow in the vagus nerve cells. Results: The number of coughs in the TRPV4 agonist GSK1016790A-treated control group was elevated compared with that in the control group, whereas the number of coughs in the TRPV4 antagonist HC067047-treated model group was significantly reduced compared with that in the chronic cough group. When the individuals in the chronic cough group were treated with A317491, PSB12062, and A804598 (P2X3,4,7 antagonists), the number of coughs was significantly decreased. This suggests that TRPV4 and P2X3, P2X4, and P2X7 receptors have an effect on cough hyper-responsiveness in guinea pigs with chronic cough. Enzyme-linked immunosorbent assay results suggested that TRPV4 antagonist and P2X3,4,7 antagonist could differentially reduce the levels of inflammatory factor SP and CGRP in alveolar lavage fluid, and TRPV4 antagonist could reduce the ATP content in the alveolar lavage fluid of guinea pigs in the model. Western blot and immunohistochemistry results showed that, in the tracheal carina and vagal ganglion, the TRPV4 and P2X3,4,7 expression was elevated in the chronic cough group compared with the control group, and could be significantly inhibited by TRPV4 antagonist. Vagus ganglion neurons were isolated, cultured, identified, and subjected to whole-cell membrane clamp assay. When ATP was given extracellularly, a significant inward current was recorded in the examined cells of individuals in the chronic cough and control groups, and the inward current induced by ATP was higher in the chronic cough group relative to the control group. This inward current (I_ATP) was differentially blocked by P2X3, P2X4, and P2X7 antagonists. Further studies revealed that TRPV4 agonists potentiated ATP-activated currents, and the potentiated currents could still be inhibited by P2X3, P2X4, and P2X7 receptor antagonists, whereas TRPV4 inhibitors partially blocked ATP-activated currents. It is suggested that TRPV4 affects P2X3, P2X4, and P2X7 receptor-mediated ATP-activated currents. Calcium imaging also showed that TRPV4 agonists induced different degrees of calcium inward currents in the vagal neurons of the chronic cough and the control group, and the calcium inward currents were more significant in the model group. Conclusions: The TRPV4-mediated purinergic signaling pathway was identified to be involved in the development of cough hypersensitivity in guinea pigs with chronic cough; i.e., TRPV4 can lead to the release of airway epithelial ATP, which can stimulate P2X receptors on the cough receptor, and further activate the sensory afferent nerves in the peripheral airway, leading to increased cough sensitivity. Full article

Over the past three decades, vagus nerve stimulation (VNS) has emerged as a promising rehabilitation therapy for a diverse range of conditions, demonstrating substantial clinical potential. This review summarizes the in vivo biological mechanisms activated by VNS and their corresponding clinical applications. Furthermore, it outlines the selection of parameters and equipment for VNS implementation. VNS exhibits anti-inflammatory effects, modulates neurotransmitter release, enhances neural plasticity, inhibits apoptosis and autophagy, maintains blood–brain barrier integrity, and promotes angiogenesis. Clinically, VNS has been utilized in the treatment of epilepsy, depression, headache, stroke, and obesity. Its potential applications extend to anti-inflammatory treatment and the management of cardiovascular and cerebrovascular diseases and various brain disorders. However, further experiments are required to definitively establish the efficacy of VNS’s various mechanisms. Additionally, there is a need to explore and identify optimal rehabilitation treatment parameters for different diseases. Full article

Background and Objectives: The Index of Response to Stimulation (IRES) is a new index that we introduce in this study to grade the effectiveness of vagus nerve stimulation in the treatment of drug-resistant epilepsy. We assessed 76 patients at 6, 12, and 18 months after VNS evaluating improvement with the IRES in four key dimensions: seizure duration decrease, seizure intensity decrease, improvement in quality of life, and seizure frequency decrease. This scale goes from 0, meaning no improvement, to 8, meaning maximal improvement, making the scale a really good measure of clinical utility. Materials and Methods: This retrospective study followed 76 patients aged 20–65, assessing changes in their IRES scores after VNS therapy using the ASPIRE SR 106 device. Therapy settings were adjusted biweekly to optimize efficacy and patient tolerance. Results: There were improvements in the control of the seizures, measured in terms of increased IRES scores. Improvements were associated with quality-of-life enhancements for the patient and a lesser frequency and intensity of the seizures, testifying further to the predictive ability of the IRES toward successful outcomes. This fact reveals that epilepsy treatment must be individual, according to the profile of the patient. Conclusions: The study confirms the IRES to be a valid tool for the assessment of the impact of VNS on drug-resistant epilepsy and promotes it as an integral part of the evaluation of the patient for personalized therapy. The findings encourage the use of IRES among the elements that support patient selection and insist on its role in the advancement of precision medicine and optimization of treatment. Full article

Background: Anxiety disorders significantly reduce patients’ quality of life. Current pharmacological treatments, primarily benzodiazepines and antidepressants, are associated with numerous side effects. Consequently, there is a continual search for alternative methods to traditional therapies that are less burdensome for patients and broaden their therapeutic options. Our objective was to determine the role of selected alternative methods in the treatment of anxiety disorders. Methods: In this review, we examined recent evidence on alternative treatments for anxiety disorders, including physical activity, mindfulness, virtual reality (VR) technology, biofeedback, herbal remedies, transcranial magnetic stimulation (TMS), cryotherapy, hyperbaric therapy, vagus nerve stimulation (VNS), 3,4-methylenedioxymethamphetamine (MDMA), electroconvulsive therapy (ECT), and eye movement desensitization and reprocessing (EMDR) therapy. For this purpose we reviewed PubMed and after initial search, we excluded works unrelated to our aim, non-orginal data and animal studies. We conducted second search to cover all minor methods. Results: We included 116 studies, which data is presented in Tables. We have investigated which methods can support treatment and which can be used as a stand-alone treatment. We assessed the risks to benefits of using alternative treatments. Conclusion: Alternative treatments significantly expand the options available to patients and clinicians, with many serving as adjuncts to traditional therapies. Among the methods presented, mindfulness has the most significant therapeutic potential. Full article

Epilepsy affects over 65 million people worldwide. One-third of people with epilepsy do not respond to medication and may benefit from surgery. Vagus nerve stimulation (VNS) is the first neuromodulation therapy for the treatment of drug-resistant epilepsy. This method is used in combination with anti-seizure medications in adults and in the pediatric population. VNS has also been demonstrated to have benefits for some epilepsy comorbidities, such as depression, and can be used in combination with other neuromodulation therapies in epilepsy. The authors present an overview of VNS physiology, patient selection, surgery and risks, neuromodulation therapy, and application to epilepsy comorbidities. Full article

The bidirectional communication network between the gut and the brain, known as the gut–brain axis, plays a crucial role in health and disease. This review explores the mechanisms underlying gut–brain interaction disorders and highlights translational therapies bridging neurology and gastroenterology. Mechanisms encompass anatomical, endocrine, humoral, metabolic, and immune pathways, with the gut microbiota exerting profound influence. Clinical evidence links gut microbiota fluctuations to mood disorders, GI disruptions, and neurodevelopmental conditions, emphasizing the microbiome’s pivotal role in shaping brain–gut interactions. Pharmacological therapies such as amitriptyline and selective serotonin reuptake inhibitors modulate neurotransmitter activity, offering relief in functional gastrointestinal disorders like irritable bowel syndrome (IBS). Non-pharmacological interventions like cognitive–behavioral therapy and hypnotherapy address maladaptive thoughts and induce relaxation, alleviating gastrointestinal symptoms exacerbated by stress. Emerging therapies include gut microbiota modulation, dietary interventions, vagus nerve stimulation, and intestinal barrier modulation, offering novel approaches to manage neurological disorders via the gastrointestinal tract. Understanding and harnessing the gut–brain axis holds promise for personalized therapeutic strategies in neurogastroenterology. Full article

BACKGROUND. Glucosensing elements are widely distributed throughout the body and relay information about circulating glucose levels to the brain via the vagus nerve. However, while anatomical wiring has been established, little is known about the physiological role of the vagus nerve in glucosensing. The contribution of the vagus nerve to inflammation in the fetus is poorly understood. Increased glucose levels and inflammation act synergistically when causing organ injury, but their interplay remains incompletely understood. We hypothesized that vagotomy (Vx) will trigger a rise in systemic glucose levels and this will be enhanced during systemic and organ-specific inflammation. Efferent vagus nerve stimulation (VNS) should reverse this phenotype. METHODS. Near-term fetal sheep (n = 57) were surgically prepared using vascular catheters and ECG electrodes as the control and treatment groups (lipopolysaccharide (LPS), Vx + LPS, Vx + LPS + selective efferent VNS). The experiment was started 72 h postoperatively to allow for post-surgical recovery. Inflammation was induced with LPS bolus intravenously (LPS group, 400 ng/fetus/day for 2 days; n = 23). For the Vx + LPS group (n = 11), a bilateral cervical vagotomy was performed during surgery; of these n = 5 received double the LPS dose, LPS800. The Vx + LPS + efferent VNS group (n = 8) received cervical VNS probes bilaterally distal from Vx in eight animals. Efferent VNS was administered for 20 min on days 1 and 2 +/10 min around the LPS bolus. Fetal arterial blood samples were drawn on each postoperative day of recovery (-72 h, -48 h, and -24 h) as well as at the baseline and seven selected time points (3–54 h) to profile inflammation (ELISA IL-6, pg/mL), insulin (ELISA), blood gas, and metabolism (glucose). At 54 h post-LPS, a necropsy was performed, and the terminal ileum macrophages’ CD11c (M1 phenotype) immunofluorescence was quantified to detect inflammation. The results are reported for p < 0.05 and for Spearman R2 > 0.1. The results are presented as the median (IQR). RESULTS. Across the treatment groups, blood gas and cardiovascular changes indicated mild septicemia. At 3 h in the LPS group, IL-6 peaked. That peak was decreased in the Vx + LPS400 group and doubled in the Vx + LPS800 group. The efferent VNS sped up the reduction in the inflammatory response profile over 54 h. The M1 macrophage activity was increased in the LPS and Vx + LPS800 groups only. The glucose and insulin concentrations in the Vx + LPS group were, respectively, 1.3-fold (throughout the experiment) and 2.3-fold higher vs. control (at 3 h). The efferent VNS normalized the glucose concentrations. CONCLUSIONS. The complete withdrawal of vagal innervation resulted in a 72-h delayed onset of a sustained increase in glucose for at least 54 h and intermittent hyperinsulinemia. Under the conditions of moderate fetal inflammation, this was related to higher levels of gut inflammation. The efferent VNS reduced the systemic inflammatory response as well as restored both the concentrations of glucose and the degree of terminal ileum inflammation, but not the insulin concentrations. Supporting our hypothesis, these findings revealed a novel regulatory, hormetic, role of the vagus nerve in the immunometabolic response to endotoxin in near-term fetuses. Full article

During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to α7 nicotinic acetylcholine receptors (α7nAChR) and inhibits α7nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an α7nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an α7nAChR-antagonist and cervical vagotomy with an α7nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-α and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy. Full article

Despite the vagus nerve stimulator (VNS) being used in neuroscience, it has recently been highlighted that it has cardioprotective functions. However, many studies related to VNS are not mechanistic in nature. This systematic review aims to focus on the role of VNS in cardioprotective therapy, selective vagus nerve stimulators (sVNS), and their functional capabilities. A systemic review of the current literature was conducted on VNS, sVNS, and their ability to induce positive effects on arrhythmias, cardiac arrest, myocardial ischemia/reperfusion injury, and heart failure. Both experimental and clinical studies were reviewed and assessed separately. Of 522 research articles retrieved from literature archives, 35 met the inclusion criteria and were included in the review. Literature analysis proves that combining fiber-type selectivity with spatially-targeted vagus nerve stimulation is feasible. The role of VNS as a tool for modulating heart dynamics, inflammatory response, and structural cellular components was prominently seen across the literature. The application of transcutaneous VNS, as opposed to implanted electrodes, provides the best clinical outcome with minimal side effects. VNS presents a method for future cardiovascular treatment that can modulate human cardiac physiology. However, continued research is needed for further insight. Full article

Background: The World Health Organization (WHO) has defined a post-COVID-19 condition. Some of these symptoms can be categorized as psychiatric long COVID-19 if they appeared in the aftermath of COVID-19, including depression, anxiety, post-traumatic stress disorder, somatic symptoms disorders such as hyperventilation syndrome, fatigue, cognitive and sleep disorders. Psychiatric and neuropsychiatric post-COVID-19 present mental health specialists with difficult challenges because of its complexity and the multiple ways in which it integrates into a singular somatic context. Methods: We conducted a systematic research paradigm from SARS-CoV-2 using LitCOVID and Web of Science to search management strategies and potential treatments for psychiatric post-COVID-19 symptoms. Results: Management strategies must be based on a multidisciplinary approach to promote the global evaluation of psychiatric and physical symptoms, systematic detection and prevention. Selective serotonin reuptake inhibitors appear to be the best choice to treat post-COVID-19 depression and anxiety disorders, and tofisopam could be helpful for anxiety. Cognitive behavioral therapy techniques adjusted to post-COVID-19 fatigue, functional remediation, extracorporeal apheresis, transcutaneous auricular vagus nerve stimulation, monoclonal antibodies, flavonoids, oxytocin or L-carnitine all represent hypothetical therapeutic avenues that remain to be evaluated in clinical trials. Conclusions: Psychiatric and neuropsychiatric post-COVID-19 symptoms occur frequently and are debilitating. Attention should be paid to this condition and studies undertaken to specify the effective treatments. Full article

Vagus nerve stimulation (VNS) is considered a potential method for anti-inflammation due to the involvement of the VN in the cholinergic anti-inflammatory pathway (CAP) formation of a connection between the central nervous system and peripheral immune cells that help relieve inflammation. However, whether a non-invasive transcutaneous auricular VNS (taVNS) modulates the inflammation levels via altering the parameter of taVNS is poorly understood. This study aimed to determine the differential inhibitory effects of taVNS on lipopolysaccharide (LPS)-induced systemic inflammation using electrical stimulation parameters such as pulse frequency and time. The taVNS-promoted CAP activity significantly recovered LPS-induced tissue injuries (lung, spleen, and intestine) and decreased inflammatory cytokine levels and tissue-infiltrated immune cells. Interestingly, the anti-inflammatory capacity of taVNS with 15 Hz was much higher than that of taVNS with 25 Hz. When a cytokine array was used to investigate the changes of inflammation and immune response-related cytokines/chemokines expression in taVNS with 15 Hz or 25 Hz treatment in LPS-induced endotoxemia in mice, most of the expression of cytokines/chemokines associated with pro-inflammation was severely decreased in taVNS with 15 Hz compared to 25 Hz. This study demonstrated that the taVNS parameter could differentially modulate the inflammation levels of animals, suggesting the importance of taVNS parameter selection for use in feasible interventions for acute inflammation treatment. Full article