Ascending Vagal Sensory and Central Noradrenergic Pathways Modulate Retrieval of Passive Avoidance Memory in Male Rats.

Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTSNA-to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

Limited evidence for anatomical contacts between intestinal GLP-1 cells and vagal neurons in male mice.

The communication between intestinal Glucagon like peptide 1 (GLP-1)-producing cells and the peripheral nervous system has garnered renewed interest considering the availability of anti-obesity and anti-diabetic approaches targeting GLP-1 signaling. While it is well-established that intestinal GLP-1 cells can exert influence through paracrine mechanisms, recent evidence suggests the possible existence of synaptic-like connections between GLP-1 cells and peripheral neurons, including those of the vagus nerve. In this study, using a reporter Phox2b-Cre-Tomato mouse model and super-resolution confocal microscopy, we demonstrated that vagal axons made apparent contacts with less than 0.5% of GLP-1 cells. Moreover, immunohistochemistry combined with super-resolution confocal microscopy revealed abundant post-synaptic density 95 (PSD-95) immunoreactivity within the enteric plexus of the lower intestines of C57/BL6 mice, with virtually none in its mucosa. Lastly, utilizing RNAScope in situ hybridization in the lower intestines of mice, we observed that GLP-1 cells expressed generic markers of secretory cells such as Snap25 and Nefm, but neither synaptic markers such as Syn1 and Nrxn2, nor glutamatergic markers such as Slc17a7. Through theoretical considerations and a critical review of the literature, we concluded that intestinal GLP-1 cells primarily communicate with vagal neurons through paracrine mechanisms, rather than synaptic-like contacts.

Anekomochi glutinous rice provides low postprandial glycemic response by enhanced insulin action via GLP-1 release and vagal afferents activation.

Glutinous rice (mochi rice), compared to non-glutinous rice (uruchi rice), exhibits a wide range of glycemic index (GI) values, from low to high. However, the underlying mechanisms behind the variation in GI values remain poorly understood. In this study, we aimed to identify rice cultivars with a low postprandial glycemic response and investigate the mechanisms, focusing on insulin and incretin hormones. We examined seven glutinous rice cultivars and three non-glutinous rice cultivars. We discovered that Anekomochi, a glutinous rice cultivar, has the lowest postprandial glycemic response. Anekomochi significantly enhanced glucagon-like peptide-1 (GLP-1) secretion while suppressing insulin secretion. These effects were completely blunted by inhibiting GLP-1 receptor signaling and denervating the common hepatic branch of vagal afferent nerves that are crucial for sensing intestinal GLP-1. Our findings demonstrate that Anekomochi markedly enhances insulin action via GLP-1 release and vagal afferent neural pathways, thereby leading to a lower postprandial glycemic response.

Noninvasive closed-loop acoustic brain-computer interface for seizure control.

Rationale: The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI. Methods: We develop a new noninvasive closed-loop acoustic brain-computer interface (aBCI) for decoding the seizure onset based on the electroencephalography and triggering ultrasound stimulation of the vagus nerve to terminate seizures. Firstly, we create the aBCI system and decode the onset of seizure via a multi-level threshold model based on the analysis of wireless-collected electroencephalogram (EEG) signals recorded from above the hippocampus. Then, the different acoustic parameters induced acoustic radiation force were used to stimulate the vagus nerve in a rat model of epilepsy-induced by pentylenetetrazole. Finally, the results of epileptic EEG signal triggering ultrasound stimulation of the vagus nerve to control seizures. In addition, the mechanism of aBCI control seizures were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). Results: In a rat model of epilepsy, the aBCI system selectively actives mechanosensitive neurons in the nodose ganglion while suppressing neuronal excitability in the hippocampus and amygdala, and stops seizures rapidly upon ultrasound stimulation of the vagus nerve. Physical transection or chemical blockade of the vagus nerve pathway abolish the antiepileptic effects of aBCI. In addition, aBCI shows significant antiepileptic effects compared to conventional vagus nerve electrical stimulation in an acute experiment. Conclusions: Closed-loop aBCI provides a novel, safe and effective tool for on-demand stimulation to treat abnormal neuronal discharges, opening the door to next generation non-invasive BCI.

The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.

BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB+Iba1+ and lipopolysaccharide (LPS)+Iba1+ cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.

In vivo imaging of vagal-induced myenteric plexus responses in gastrointestinal tract with an optical window.

The vagus nerve (VN) extensively innervates the gastric enteric nervous system (ENS), but its influence on gastric ENS functionality and motility in vivo remains unclear due to technical challenges. Here we describe a method for stable, long-term observation of gastric ENS activity and muscle dynamics at cellular resolution, which can also be extended to intestinal applications. This method involves ENS-specific labeling and the implantation of an abdominal wall window for optical recording in male mice. In vivo calcium imaging reveals a linear relationship between vagal stimulation frequency and myenteric neuron activation in gastric antrum. Furthermore, the motility of gastric antrum is significantly enhanced and shows a positive correlation with the intensity and number of activated myenteric neurons. While vagal stimulation also activates proximal colonic myenteric neurons, this activation is not frequency-dependent and does not induce proximal colonic motility. The method and results provide important insights into VN-ENS interactions in vivo, advancing our understanding of gastrointestinal motility regulation.

Neurophysiological Basis of Electroacupuncture Stimulation in the Treatment of Cardiovascular-Related Diseases: Vagal Interoceptive Loops.

PURPOSE: The vagal sensory nerve (VSN) is an essential interoceptive pathway that is connected to every level of the body. Its intricate genetic coding provides sustenance for physiological processes, including controlling blood pressure and respiration. Electroacupuncture (EA) is a proven surface stimulation therapy that can regulate vagal nerve activity, which can effectively prevent cardiovascular diseases. A growing number of studies have concentrated on the mapping of VSN codes, but little is known, and the physiological background of how EA influences interoceptive has not been fully explored. METHOD: Here, we incorporate the hypothesized interaction among EA targets, VSNs, and the heart. This offers suggestions for using a versatile and focused EA strategy to modify vagal interoceptive awareness to enhance cardiovascular conditions. We first clarified the major role of vagal nerve in the control of cardiac activity. Additionally, we clarified the multidimensional coding pattern in the VSNs, revealing that the targeted control of multimodal interoceptive is the functional basis of the synchronization of cardiovascular system. FINDING: We propose a strategy in which EA of the VSNs is employed to activate the interoceptive loop and reduce the risk of cardiovascular disease.

Baroreflex Sensitivity in Patients With Laryngopharyngeal Dysfunction-The Overwhelmed Vagus Hypothesis.

Importance: The autonomic nervous system maintains internal stability by concurrently prioritizing and managing different functions. It is currently not known whether dysfunction at the aerodigestive junction could overwhelm autonomic control and impair other functions. Objective: To compare baroreflex sensitivity, a prognostically significant index of the autonomic system's ability to stabilize blood pressure, between patients with predominantly esophagogastric (digestive) and patients with predominantly laryngopharyngeal (aerodigestive) symptoms. Design, Setting, and Participants: A cross-sectional study, between 2018 and 2019, of adults undergoing esophagal manometry or transnasal panendoscopy was carried out in a specialist center. The analysis took place between 2023 and 2024. Main Outcomes and Measures: Heart rate and blood pressure were recorded and baroreflex sensitivity and heart rate variability were derived. Esophageal physiology was assessed with high-resolution manometry. Results: There were 30 and 23 patients in the digestive and aerodigestive groups, respectively. The mean (SD) age was 61 (15) years and there were 26 women and 27 men. Compared with patients in the digestive group, more patients in the aerodigestive group had voice or throat symptoms and fewer had classic reflux symptoms (odds ratio [OR], 5.65; 95% CI, 1.82-17.5; OR, 2.07; 95% CI, 1.28-3.33; and OR, 0.60; 95% CI, 0.38-0.95, respectively). Patients in the aerodigestive group had higher mean (SD) resting heart rate (93 [17] vs 75 [13] min-1; difference of means, -18 min-1; 95% CI, -26 to -10), lower resting mean (SD) arterial pressure (94 [16] vs 104 [23] mm Hg, OR, 10; 95% CI, -1 to 21), lower mean (SD) baroreflex sensitivity (3.77 [0.79] vs 9.76 [2.92] s-3mm Hg-1; OR, 6.0 s-3mmHg-1; 95% CI, 4.7-7.2), and lower mean (SD) parasympathetic-spectrum heart rate variability (0.68 [0.15] vs 1.30 [0.53]; OR, 0.62; 95% CI, 0.39-0.85). There was a correlation between reduced lower esophageal relaxation (integrated relaxation pressure) and reduced baroreflex sensitivity (r = -0.33; 95% CI, -0.58 to -0.03). Conclusions: In this cross-sectional study of adults undergoing esophageal manometry or transnasal panendoscopy, patients with laryngopharyngeal symptoms had reduced baroreflex sensitivity, indicating diminished vagal control compared with patients with esophagogastric symptoms. The overwhelmed vagus hypothesis may explain these responses by considering autonomic functions as competing consumers of the finite regulatory resources of a common controller. The regulatory demands of maintaining a safe airway with concurrent laryngopharyngeal sensorimotor dysfunction, superadded to baseline demands for dual speech and aerodigestive control, could overwhelm and force the system to deprioritize less immediate functions like esophageal relaxation and the baroreflex. Measuring baroreflex sensitivity, now possible in routine clinical practice, could enable phenotyping and objective outcome assessment for laryngopharyngeal dysfunction. A neurophysiological model for considering laryngopharyngeal sensorimotor dysfunction could in turn move patient care toward a more holistic autonomic health footing.

Serotonergic modulation of swallowing in a complete fly vagus nerve connectome.

How the body interacts with the brain to perform vital life functions, such as feeding, is a fundamental issue in physiology and neuroscience. Here, we use a whole-animal scanning transmission electron microscopy volume of Drosophila to map the neuronal circuits that connect the entire enteric nervous system to the brain via the insect vagus nerve at synaptic resolution. We identify a gut-brain feedback loop in which Piezo-expressing mechanosensory neurons in the esophagus convey food passage information to a cluster of six serotonergic neurons in the brain. Together with information on food value, these central serotonergic neurons enhance the activity of serotonin receptor 7-expressing motor neurons that drive swallowing. This elemental circuit architecture includes an axo-axonic synaptic connection from the glutamatergic motor neurons innervating the esophageal muscles onto the mechanosensory neurons that signal to the serotonergic neurons. Our analysis elucidates a neuromodulatory sensory-motor system in which ongoing motor activity is strengthened through serotonin upon completion of a biologically meaningful action, and it may represent an ancient form of motor learning.

Highly-stable, injectable, conductive hydrogel for chronic neuromodulation.

Electroceuticals, through the selective modulation of peripheral nerves near target organs, are promising for treating refractory diseases. However, the small sizes and the delicate nature of these nerves present challenges in simplifying the fixation and stabilizing the electrical-coupling interface for neural electrodes. Herein, we construct a robust neural interface for fine peripheral nerves using an injectable bio-adhesive hydrogel bioelectronics. By incorporating a multifunctional molecular regulator during network formation, we optimize the injectability and conductivity of the hydrogel through fine-tuning reaction kinetics and multi-scale interactions within the conductive network. Meanwhile, the mechanical and electrical stability of the hydrogel is achieved without compromising its injectability. Minimal tissue damage along with low and stable impedance of the injectable neural interface enables chronic vagus neuromodulation for myocardial infarction therapy in the male rat model. Our highly-stable, injectable, conductive hydrogel bioelectronics are readily available to target challenging anatomical locations, paving the way for future precision bioelectronic medicine.

Associations of luteal phase changes in vagally mediated heart rate variability with premenstrual emotional changes.

BACKGROUND: A recent meta-analysis revealed that vagally mediated heart rate variability (vmHRV; a biomarker of emotion regulation capacity) significantly decreases in the luteal phase of the menstrual cycle. As two follow-up studies suggest, these vmHRV decreases are driven primarily by increased luteal progesterone (P4). However, analyses also revealed significant interindividual differences in vmHRV reactivity to the cycle, which is in line with longstanding evidence for interindividual differences in mood sensitivity to the cycle. The present study begins to investigate whether these interindividual differences in vmHRV cyclicity can explain who is at higher risk of showing premenstrual emotional changes. We expected a greater degree of midluteal vmHRV decrease to be predictive of a greater premenstrual increase in negative affect. METHODS: We conducted an observational study with a naturally cycling community sample (N = 31, M = 26.03 years). Over a span of six weeks, participants completed (a) daily ratings of negative affect and (b) counterbalanced lab visits in their ovulatory, midluteal, and perimenstrual phases. Lab visits were scheduled based on positive ovulation tests and included assessments of baseline vmHRV and salivary ovarian steroid levels. RESULTS: In line with previous research, multilevel models suggest that most of the sample shows ovulatory-to-midluteal vmHRV decreases which, however, were not associated with premenstrual emotional changes. Interestingly, it was only the subgroup with luteal increases in vmHRV whose negative affect markedly worsened premenstrually and improved postmenstrually. CONCLUSION: The present study begins to investigate cyclical changes in vmHRV as a potential biomarker of mood sensitivity to the menstrual cycle. The results demonstrate a higher level of complexity in these associations than initially expected, given that only atypical midluteal increases in vmHRV are associated with greater premenstrual negative affect. Potential underlying mechanisms are discussed, among those the possibility that luteal vmHRV increases index compensatory efforts to regulate emotion in those with greater premenstrual negative affect. However, future studies with larger and clinical samples and more granular vmHRV assessments should build on these findings and further explore associations between vmHRV cyclicity and menstrually related mood changes.

Evaluation of low vagally-mediated heart rate variability as an early marker of depression risk.

BACKGROUND: Both low vagally-mediated heart rate variability (HRV) and depression have been shown to be risk factors for cardiovascular disease (CVD). We recently identified an HRV cutpoint below which persons have an increased risk for several cardiometabolic disorders. However, no cutpoint exists to identify those at risk for depression. METHODS: The association between daytime HRV and diagnostically validated depression cutoffs using the five-item World Health Organization Well-being Index (WHO-5) was examined in adults from the Mannheim Industrial Cohort Study (n = 9973; Mage = 41.9[10.9]; 20 % women [n = 1934]). The aim was to identify HRV cutpoints for individuals who may have clinical depression. RESULTS: Regression adjusting for age, sex, and linear trend showed a significant quadratic association between depression, indexed by WHO-5 scores and HRV, indexed by the root mean square successive differences (RMSSD) in milliseconds (ms) (p < 0.001). Logistic regression models adjusting for age, sex, and heart period (i.e., inter-beat intervals) compared the clinically depressed (WHO-5 ≤ 28) and those with a screening diagnosis of depression (WHO-5 ≤ 50) to the rest of the population. Significant odds ratios suggested two RMSSD values 25 ± 2 ms (OR = 1.39 [1.17, 1.64]) and 35 ± 2 ms (OR = 1.17 [1.02, 1.34]) that may be used to identify those with an elevated risk for depression. LIMITATIONS: The sample was primarily German men. Fitness and anti-depressant use were not available. CONCLUSIONS: As HRV is a brief measure that can be used in clinical settings, our HRV cutpoints have implications for the early detection of those at risk for psychological and cardiometabolic disorders.

Disturbances of the gut microbiota-derived tryptophan metabolites as key actors in vagotomy-induced mastitis in mice.

Previous studies have demonstrated that gut microbiota dysbiosis promotes the development of mastitis. The interaction of the vagus nerve and gut microbiota endows host homeostasis and regulates disease development, but whether the vagus nerve participates in the pathogenesis of mastitis is unclear. Here, vagotomized mice exhibit disruption of the blood-milk barrier and mammary gland inflammation. Notably, mastitis and barrier damage caused by vagotomy are dependent on the gut microbiota, as evidenced by antibiotic treatment and fecal microbiota transplantation. Vagotomy significantly alters the gut microbial composition and tryptophan metabolism and reduces the 5-hydroxyindole acetic acid (5-HIAA) level. Supplementation with 5-HIAA alleviates vagotomy-induced mastitis, which is associated with the activation of the aryl hydrocarbon receptor (AhR) and subsequent inhibition of the NF-κB pathway. Collectively, our findings indicate the important role of the vagus-mediated gut-mammary axis in the pathogenesis of mastitis and imply a potential strategy for the treatment of mastitis by targeting the vagus-gut microbiota interaction.

Vagal nerve stimulation potential therapeutic benefits in acute lung rejection and transplantation.

Allograft rejection, accompanied by a rise in proinflammatory cytokines, is a leading cause of morbidity and mortality after lung transplantation. Immunosuppressive treatments are routinely employed as an effective way to prevent rejection, however, there is still an unmet need to develop new strategies to reduce the damage caused to transplanted organs by innate inflammatory responses. Recent research has shown that activating the vagus nerve's efferent arm regulates cytokine production and improves survival in experimental conditions of cytokine excess, such as sepsis, hemorrhagic shock, ischemia-reperfusion injury, among others. The cholinergic anti-inflammatory pathway can provide a localized, fast, and discrete response to inflammation by controlling the neuroimmune response and preventing excessive inflammation. This review intends to assess and discuss, the influence of noninvasive vagal nerve stimulation for prophylactic measures and supporting treatment in patients undergoing organ transplantation rejection with a prominent T-cell mediated immune response as a means of attenuating inflammation and leukocyte infiltration of the graft vessels.

Muscarinic and nicotinic receptors stimulation by vagus nerve stimulation ameliorates trastuzumab-induced cardiotoxicity via reducing programmed cell death in rats.

Despite its efficacy in human epidermal growth factor receptor 2 positive cancer treatment, trastuzumab-induced cardiotoxicity (TIC) has become a growing concern. Due to the lack of cardiomyocyte regeneration and proliferation in adult heart, cell death significantly contributes to cardiovascular diseases. Cardiac autonomic modulation by vagus nerve stimulation (VNS) has shown cardioprotective effects in several heart disease models, while the effects of VNS and its underlying mechanisms against TIC have not been found. Forty adult male Wistar rats were divided into 5 groups: (i) control without VNS (CSham) group, (ii) trastuzumab (4 mg/kg/day, i.p.) without VNS (TSham) group, (iii) trastuzumab + VNS (TVNS) group, (iv) trastuzumab + VNS + mAChR blocker (atropine; 1 mg/kg/day, ip, TVNS + Atro) group, and (v) trastuzumab + VNS + nAChR blocker (mecamylamine; 7.5 mg/kg/day, ip, TVNS + Mec) group. Our results showed that trastuzumab induced cardiac dysfunction by increasing autonomic dysfunction, mitochondrial dysfunction/dynamics imbalance, and cardiomyocyte death including apoptosis, autophagic deficiency, pyroptosis, and ferroptosis, which were notably alleviated by VNS. However, mAChR and nAChR blockers significantly inhibited the beneficial effects of VNS on cardiac autonomic dysfunction, mitochondrial dysfunction, cardiomyocyte apoptosis, pyroptosis, and ferroptosis. Only nAChR could counteract the protective effects of VNS on cardiac mitochondrial dynamics imbalance and autophagy insufficiency. Therefore, VNS prevented TIC by rebalancing autonomic activity, ameliorating mitochondrial dysfunction and cardiomyocyte death through mAChR and nAChR activation. The current study provides a novel perspective elucidating the potential treatment of VNS, thus also offering other pharmacological therapeutic promises in TIC patients.

Asymptomatic Purely Intracranial Vagal Schwannoma: Clinical Case Report and Literature Review.

Vagus nerve schwannoma is an infrequently occurring schwannoma, in which a distinct subtype exists wherein the tumor is confined to the cerebellomedullary cistern without invading the jugular foramen. This unique tumor is called purely intracranial vagal schwannoma. In this case report, we present a case of purely intracranial vagal schwannoma in its asymptomatic early phase, incidentally discovered during surgery performed on a patient with hemifacial spasm. Because of the small size of the tumor, we definitively recognized that it originated from the second rootlet on the caudal side. The tumor was totally resected uneventfully and a favorable prognosis was achieved. Furthermore, we conducted a comprehensive literature review to summarize the classification, origin, and surgical complications associated with this rare tumor type. Based on our literature review, we propose that: 1) the origin of tumor is related to the time of onset of symptoms, 2) nearly all purely intracranial vagal schwannomas can be entirely resected and favorable prognosis can be achieved, and 3) surgeons should be aware of potential cardiovascular complications during surgical procedures.

Stress-sensitive neural circuits change the gut microbiome via duodenal glands.

Negative psychological states impact immunity by altering the gut microbiome. However, the relationship between brain states and microbiome composition remains unclear. We show that Brunner's glands in the duodenum couple stress-sensitive brain circuits to bacterial homeostasis. Brunner's glands mediated the enrichment of gut Lactobacillus species in response to vagus nerve stimulation. Cell-specific ablation of the glands markedly suppressed Lactobacilli counts and heightened vulnerability to infection. In the forebrain, we mapped a vagally mediated, polysynaptic circuit connecting the central nucleus of the amygdala to Brunner's glands. Chronic stress suppressed central amygdala activity and phenocopied the effects of gland lesions. Conversely, excitation of either the central amygdala or parasympathetic vagal neurons activated Brunner's glands and reversed the effects of stress on the gut microbiome and immunity. The findings revealed a tractable brain-body mechanism linking psychological states to host defense.

Treating heart failure by targeting the vagus nerve.

Increased sympathetic and reduced parasympathetic nerve activity is associated with disease progression and poor outcomes in patients with chronic heart failure. The demonstration that markers of autonomic imbalance and vagal dysfunction, such as reduced heart rate variability and baroreflex sensitivity, hold prognostic value in patients with chronic heart failure despite modern therapies encourages the research for neuromodulation strategies targeting the vagus nerve. However, the approaches tested so far have yielded inconclusive results. This review aims to summarize the current knowledge about the role of the parasympathetic nervous system in chronic heart failure, describing the pathophysiological background, the methods of assessment, and the rationale, limits, and future perspectives of parasympathetic stimulation either by drugs or bioelectronic devices.

EndoFLIP evaluation of the pylorus during minimal invasive Ivor-Levis esophagectomy.

BACKGROUND/AIMS: During esophagectomy for malignancy, the anterior and posterior branches of the vagus nerve are transected in order to achieve surgical radicality. This leads to loss of central nervous system-control of the pylorus which may lead to delayed gastric emptying. We aimed to investigate the feasibility of the EndoFLIP technique for assessment of pyloric biomechanical properties in patients undergoing esophagectomy. METHODS: A feasibility study in six patients undergoing surgery was conducted. EndoFLIP measurements were carried out preoperative (Pre-op), after surgical resection (Post-op) and following prophylactic balloon dilatation of the pylorus (Post-dil). By measuring the cross-sectional area and pressure of the pylorus the pyloric compliance and the incremental pressure-strain elastic modulus (Ep) were calculated. RESULTS: Placing the catheter in the pyloric region was successfully achieved in all six patients. No complications were observed. Resection of the esophagus increased the incremental pyloric elastic modulus (Ep) from 0.59 ± 0.18 kPa to 0.99 ± 0.34 kPa (p = 0.03). After dilatation, the Ep was reduced to 0.53 ± 0.23 kPa (p = 0.04), which was close to Pre-op (p = 0.62). The pyloric compliance showed a similar pattern as that found for Ep. CONCLUSION: The EndoFLIP system holds promise for assessment of biomechanics of the pyloric region in patients undergoing esophagectomy for cancer.

Self-Adhesive and Self-Sustainable Bioelectronic Patch for Physiological Feedback Electronic Modulation of Soft Organs.

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.