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World Journal of Surgical Oncology Jul 2023The interplay between the nervous system and cancer plays an important role in the initiation and progression of gastric cancer. Few studies have presented evidence that...
BACKGROUND
The interplay between the nervous system and cancer plays an important role in the initiation and progression of gastric cancer. Few studies have presented evidence that the sympathetic nervous system inhibits the occurrence and development of gastric cancer while the parasympathetic nervous system promotes the growth of gastric cancer. To investigate the effect of vagotomy, which is the resection of a parasympathetic nerve innervating the stomach, on the progression of gastric cancer, a retrospective study was conducted comparing the prognosis of simple palliative gastrojejunostomy (PGJ) and palliative gastrojejunostomy with vagotomy (PGJV).
METHODS
From January 01, 2000, to December 31, 2021, the medical records of patients who underwent PGJ or PGJV because of gastric outlet obstruction due to incurable advanced gastric cancer at the Yeungnam University Medical Center were retrospectively reviewed. Patients were divided into two groups: locally unresectable gastric cancer (LUGC) or gastric cancer with distant metastasis (GCDM), according to the reason for gastrojejunostomy, and factors affecting overall survival (OS) were analyzed.
RESULTS
There was no significant difference in surgical outcomes and postoperative complications between the patients with PGJV and patients with PGJ. In univariate analysis, vagotomy was not a significant factor for OS in the GCDM group (HR 1.14, CI 0.67-1.94, p value 0.642), while vagotomy was a significant factor for OS in the LUGC group (HR 0.38, CI 0.15-0.98, p value 0.045). In multivariate analysis, when vagotomy is performed together with PGJ for LUGC, the OS can be significantly extended (HR 0.25, CI 0.09-0.068, p value 0.007).
CONCLUSIONS
When PGJ for LUGC was performed with vagotomy, additional survival benefits could be achieved with low complication risk. However, to confirm the effect of vagotomy on the growth of gastric cancer, further prospective studies using large sample sizes are essential.
Topics: Humans; Retrospective Studies; Stomach Neoplasms; Case-Control Studies; Palliative Care; Prospective Studies; Vagotomy; Gastric Outlet Obstruction
PubMed: 37480111
DOI: 10.1186/s12957-023-03111-9 -
Journal of Clinical Medicine Jun 2023Marginal ulcer (MU) is a potential complication following Roux-en-Y gastric bypass (RYGB), with a mean prevalence of 4.6%. Early identification and prompt intervention... (Review)
Review
Marginal ulcer (MU) is a potential complication following Roux-en-Y gastric bypass (RYGB), with a mean prevalence of 4.6%. Early identification and prompt intervention are crucial to mitigating further complications. The pathophysiology of MU is complex and involves multiple factors, including smoking, infection, non-steroidal anti-inflammatory drug (NSAID) use, and larger pouch size. Patients with MU may experience acute or chronic abdominal pain. Rarely, they may present with a complication from the ulceration, such as bleeding, perforation, or strictures. Following diagnosis by endoscopy, management of MU typically involves modification of risk factors and medical therapy focused on proton pump inhibitors. In case of complicated ulcers, surgical intervention is often required for the repair of the perforation or resection of the stricture. For recurrent or recalcitrant ulcers, endoscopic coverage of the ulcer bed, resection of the anastomosis, and abdominal or thoracoscopic truncal vagotomy may be considered. This review aims at providing an overview of the etiology, diagnosis, and management of MU after RYGB.
PubMed: 37445371
DOI: 10.3390/jcm12134336 -
Nature Aug 2023The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with...
The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance. Here, we show that antigen-specific avoidance behaviour in inbred mice is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.
Topics: Animals; Mice; Allergens; Avoidance Learning; Hypersensitivity; Immunoglobulin E; Mast Cells; Stomach; Vagotomy; Immunity, Innate; Immunity, Mucosal; Th2 Cells; Cytokines; Leukotrienes; Intestine, Small
PubMed: 37438525
DOI: 10.1038/s41586-023-06188-0 -
Science Advances Jul 2023The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated...
The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated nanoparticle translocation between organs is poorly understood. Here, we show that peripheral nerve fibers act as direct conduits for silver nanomaterials (Ag NMs) translocation from the gut to the CNS in both mice and rhesus monkeys. After oral gavage, Ag NMs are significantly enriched in the brain and spinal cord of mice with particle state however do not efficiently enter the blood. Using truncal vagotomy and selective posterior rhizotomy, we unravel that the vagus and spinal nerves mediate the transneuronal translocation of Ag NMs from the gut to the brain and spinal cord, respectively. Single-cell mass cytometry analysis revealed that enterocytes and enteric nerve cells take up significant levels of Ag NMs for subsequent transfer to the connected peripheral nerves. Our findings demonstrate nanoparticle transfer along a previously undocumented gut-CNS axis mediated by peripheral nerves.
Topics: Animals; Mice; Silver; Central Nervous System; Spinal Cord; Peripheral Nerves; Nanostructures
PubMed: 37418525
DOI: 10.1126/sciadv.adg2252 -
Progress in Brain Research 2023Neuroinflammation plays a key role in the pathogenesis of major depressive disorder (MDD), including treatment-resistant depression (TRD). Patients with TRD have higher...
Neuroinflammation plays a key role in the pathogenesis of major depressive disorder (MDD), including treatment-resistant depression (TRD). Patients with TRD have higher levels of inflammatory biomarkers compared with responders to antidepressants. Multiple lines of evidence suggest that the gut-microbiota-brain axis via the vagus nerve plays a key role in neuroinflammation. Preclinical and clinical data suggest that fecal microbiota transplantation (FMT) from MDD patients or rodents with depression-like behaviors cause depression-like behaviors in rodents through systemic inflammation. Importantly, subdiaphragmatic vagotomy blocked these depression-like phenotypes and systemic inflammation in rodents after FMT of depression-related microbes. Subdiaphragmatic vagotomy also blocked the antidepressant-like effects of serotonergic antidepressants in rodents. Preclinical findings suggest that the new antidepressant, (R)-ketamine (or arketamine), may restore the altered composition of gut microbiota in rodents with depression-like behaviors, contributing to the beneficial effects of arketamine. In this chapter, the author reviews the role of the vagus nerve-dependent gut-microbiota-brain axis in depression (including TRD), and also discuss the potential of FMT, vagus nerve stimulation, and arketamine for the treatment of TRD.
Topics: Humans; Depression; Depressive Disorder, Major; Neuroinflammatory Diseases; Microbiota; Antidepressive Agents; Inflammation; Vagus Nerve; Brain
PubMed: 37414494
DOI: 10.1016/bs.pbr.2023.01.003 -
Journal of Neuroinflammation Jul 2023Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve,...
BACKGROUND
Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, the interaction of the vagus nerve and the celiac ganglia requires a unique interaction of parasympathetic and sympathetic inputs, making this putative mechanism of brain-spleen interaction controversial. BODY: As neuropeptides can be expressed at relatively high levels in neurons, we reasoned that DMN neuropeptide immunoreactivity could be used to determine their target innervation. Employing immunohistochemistry, subdiaphragmatic vagotomy, viral tract tracing, CRISPR-mediated knock-down, and functional assays, we show that cocaine and amphetamine-regulated transcript (CART) peptide-expressing projection neurons in the caudal DMN directly innervate the spleen. In response to lipopolysaccharide (LPS) stimulation, CART acts to reduce inflammation, an effect that can be augmented by intrasplenic administration of a synthetic CART peptide. These in vivo effects could be recapitulated in cultured splenocytes, suggesting that these cells express the as yet unidentified CART receptor(s).
CONCLUSION
Our results provide evidence for direct connections between the caudal DMN and spleen. In addition to acetylcholine, these neurons express the neuropeptide CART that, once released, acts to suppress inflammation by acting directly upon splenocytes.
Topics: Humans; Spleen; Neurons; Neuropeptides; Vagus Nerve; Inflammation
PubMed: 37403174
DOI: 10.1186/s12974-023-02838-2 -
Journal of Hazardous Materials Sep 2023Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of...
Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of research has demonstrated that PM exposure may induce various negative health effects via pulmonary and systemic inflammations. To study the potential role of the CAP in mediating PM-induced effects, mice were treated with vagus nerve electrical stimulation (VNS) to activate the CAP before diesel exhaust PM (DEP) instillation. Analysis of pulmonary and systemic inflammations in mice demonstrated that VNS significantly reduced the inflammatory responses triggered by DEP. Meanwhile, inhibition of the CAP by vagotomy aggravated DEP-induced pulmonary inflammation. The flow cytometry results showed that DEP influenced the CAP by altering the Th cell balance and macrophage polarization in spleen, and in vitro cell co-culture experiments indicated that this DEP-induced change on macrophage polarization may act via the splenic CD4 T cells. To further confirm the effect of alpha7 nicotinic acetylcholine receptor (α7nAChR) in this pathway, mice were then treated with α7nAChR inhibitor (α-BGT) or agonist (PNU282987). Our results demonstrated that specific activation of α7nAChR with PNU282987 effectively alleviated DEP-induced pulmonary inflammation, while specific inhibition of α7nAChR with α-BGT exacerbated the inflammatory markers. The present study suggests that PM have an impact on the CAP, and CAP may play a critical function in mediating PM exposure-induced inflammatory response. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Topics: Mice; Animals; Vehicle Emissions; alpha7 Nicotinic Acetylcholine Receptor; Neuroimmunomodulation; Inflammation; Pneumonia; Particulate Matter
PubMed: 37392642
DOI: 10.1016/j.jhazmat.2023.131951 -
European Journal of Pharmacology Aug 2023The vagus nerve is a major pathway in the body that is responsible for regulating the activity of the parasympathetic nervous system, which plays an important role in...
The vagus nerve is a major pathway in the body that is responsible for regulating the activity of the parasympathetic nervous system, which plays an important role in mood disorders including anxiety and depression. Fluoxetine, also known as Prozac, is widely used to treat depression. Nevertheless, there are few studies on the vagus nerve-mediated action of fluoxetine. In this study, we aimed to investigate the vagus nerve-dependent actions of fluoxetine in mice with restraint stress-induced or antibiotics-induced anxiety- and depression-like behaviors. Compared to sham operation, vagotomy alone did not exhibit significant effects on behavioral changes and serotonin-related biomarkers in mice not exposed to stress, antibiotics, or fluoxetine. Oral administration of fluoxetine significantly alleviated anxiety- and depression-like behaviors. However, celiac vagotomy significantly attenuated the anti-depressive effects of fluoxetine. The vagotomy also inhibited the effect of fluoxetine to attenuate restraint stress- or cefaclor-induced reduction in serotonin levels and Htr1a mRNA expression in the hippocampus. These findings suggest that the vagus nerve may regulate the efficacy of fluoxetine for depression.
Topics: Mice; Animals; Fluoxetine; Depression; Serotonin; Anxiety; Vagus Nerve; Hippocampus
PubMed: 37331682
DOI: 10.1016/j.ejphar.2023.175862 -
BioRxiv : the Preprint Server For... May 2023The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute...
BACKGROUND
The vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN) as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications, but the anti-inflammatory efficacy of electrical DMN stimulation (eDMNS) was not previously investigated. Here, we examined the effects of eDMNS on heart rate (HR) and cytokine levels in murine endotoxemia as well as the cecal ligation and puncture (CLP) model of sepsis.
METHODS
Anesthetized male 8-10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (50, 250 or 500 μA and 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24h after CLP. CLP survival was monitored for 14 days.
RESULTS
Either left or right eDMNS at 250 μA and 500 μA decreased HR, compared with pre- and post-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and were not associated with serum corticosterone alterations. Right side eDMNS suppressed serum TNF levels but had no effects on serum IL-10 and on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum TNF and IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice.
CONCLUSIONS
For the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation and these effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.
PubMed: 37292846
DOI: 10.1101/2023.05.17.541191 -
American Journal of Physiology. Lung... Jul 2023Children born to obese mothers are prone to develop asthma and airway hyperresponsiveness, but the mechanisms behind this are unclear. Here we developed a mouse model of...
Children born to obese mothers are prone to develop asthma and airway hyperresponsiveness, but the mechanisms behind this are unclear. Here we developed a mouse model of maternal diet-induced obesity that recapitulates metabolic abnormalities seen in humans born to obese mothers. Offspring of dams fed a high-fat diet (HFD) showed increased adiposity, hyperinsulinemia, and insulin resistance at 16 wk of age despite being fed only a regular diet (RD). Bronchoconstriction induced by inhaled 5-hydroxytriptamine was also significantly increased in offspring of HFD-fed versus RD-fed dams. Increased bronchoconstriction was blocked by vagotomy, indicating this reflex was mediated by airway nerves. Three-dimensional (3-D) confocal imaging of tracheas collected from 16-wk-old offspring showed that both epithelial sensory innervation and substance P expression were increased in the offspring of HFD-fed dams compared with offspring of RD-fed dams. For the first time, we show that maternal high-fat diet increases airway sensory innervation in offspring, leading to reflex airway hyperresponsiveness. Our study reveals a novel potential mechanism, by which maternal high-fat diet increases the risk and severity of asthma in offspring. We found that exposure to maternal high-fat diet in mice leads to hyperinnervation of airway sensory nerves and increased reflex bronchoconstriction in offspring fed a regular diet only. These findings have important clinical implications and provide new insights into the pathophysiology of asthma, highlighting the need for preventive strategies in this patient population.
Topics: Humans; Female; Child; Animals; Mice; Diet, High-Fat; Adult Children; Bronchoconstriction; Prenatal Exposure Delayed Effects; Obesity; Reflex; Asthma; Respiratory Hypersensitivity
PubMed: 37280517
DOI: 10.1152/ajplung.00115.2023