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Nutrients May 2023During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate...
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 ( > 0.999). There was a trend in aggravation of LIS after cervical vagotomy ( = 0.051), even after an α7nAChR-agonist ( = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury ( = 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 ( = 0.012) and selective vagotomy ( = 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.
Topics: Rats; Animals; Lipopolysaccharides; alpha7 Nicotinic Acetylcholine Receptor; Vagus Nerve; Vagotomy; Acute Lung Injury
PubMed: 37242210
DOI: 10.3390/nu15102327 -
Biomedicines Apr 2023GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body...
GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.
PubMed: 37238993
DOI: 10.3390/biomedicines11051322 -
Temperature (Austin, Tex.) 2023We identified the neural pathway of the hyperthermic response to TRPV1 antagonists. We showed that hyperthermia induced by i.v. AMG0347, AMG 517, or AMG8163 did not...
We identified the neural pathway of the hyperthermic response to TRPV1 antagonists. We showed that hyperthermia induced by i.v. AMG0347, AMG 517, or AMG8163 did not occur in rats with abdominal sensory nerves desensitized by pretreatment with a low i.p. dose of resiniferatoxin (RTX, TRPV1 agonist). However, neither bilateral vagotomy nor bilateral transection of the greater splanchnic nerve attenuated AMG0347-induced hyperthermia. Yet, this hyperthermia was attenuated by bilateral high cervical transection of the spinal dorsolateral funiculus (DLF). To explain the extra-splanchnic, spinal mediation of TRPV1 antagonist-induced hyperthermia, we proposed that abdominal signals that drive this hyperthermia originate in skeletal muscles - not viscera. If so, in order to prevent TRPV1 antagonist-induced hyperthermia, the desensitization caused by i.p. RTX should spread into the abdominal-wall muscles. Indeed, we found that the local hypoperfusion response to capsaicin (TRPV1 agonist) in the abdominal-wall muscles was absent in i.p. RTX-desensitized rats. We then showed that the most upstream (lateral parabrachial, LPB) and the most downstream (rostral raphe pallidus) nuclei of the intrabrain pathway that controls autonomic cold defenses are also required for the hyperthermic response to i.v. AMG0347. Injection of muscimol (inhibitor of neuronal activity) into the LPB or injection of glycine (inhibitory neurotransmitter) into the raphe blocked the hyperthermic response to i.v. AMG0347, whereas i.v. AMG0347 increased the number of c-Fos cells in the raphe. We conclude that the neural pathway of TRPV1 antagonist-induced hyperthermia involves TRPV1-expressing sensory nerves in trunk muscles, the DLF, and the same LPB-raphe pathway that controls autonomic cold defenses.
PubMed: 37187834
DOI: 10.1080/23328940.2023.2171671 -
Khirurgiia 2023To analyze immediate and long-term postoperative results in patients with hiatal hernia complicated by short esophagus.
OBJECTIVE
To analyze immediate and long-term postoperative results in patients with hiatal hernia complicated by short esophagus.
MATERIAL AND METHODS
We prospectively analyzed postoperative outcomes in 113 patients with hiatal hernia who underwent surgery between 2013 and 2021. The main group consisted of 54 patients with length of intra-abdominal segment of esophagus <4 cm who underwent Collis procedure or esophagus >4 cm and indications for Nissen fundoplication cuff. The control group consisted of 59 patients and indications for esophageal lengthening procedure only if length of intra-abdominal segment of esophagus was less than 2 cm. This surgery was started with anterolateral vagotomy, and Collis procedure was performed in case of ineffective vagotomy. Nissen fundoplication was performed for abdominal segment of esophagus >2 cm.
RESULTS
In the main group, 17 (31.5%) patients with intra-abdominal segment of esophagus <4 cm required Collis procedure. In the control group, length of intra-abdominal segment of esophagus <2 cm was observed in 6 (10.2%) patients. In all cases, anterolateral vagotomy was performed. Surgery time was 189 (80-290) and 136 (90-320) min, respectively (=0.001). Postoperative complications in the main group occurred in 8 (14.8%) patients, in the control group - 4 (6.8%) patients (=0.281). One (1.7%) patient died in the control group. The follow-up period was 38 (12-66) months. In long-term period, recurrence developed in 2 (3.7%) and 11 (20%) patients, respectively (=0.026). High satisfaction with postoperative outcomes was observed in 51 (94.4%) and 46 (79.3%) patients, respectively (=0.038).
CONCLUSION
Uncorrected shortening of the esophagus can be one of the main risk factors of recurrence in long-term period. Expanding the indications for Collis gastroplasty can reduce the incidence of poor outcomes without affecting the incidence of postoperative complications.
Topics: Humans; Hernia, Hiatal; Gastroesophageal Reflux; Prospective Studies; Treatment Outcome; Esophageal Diseases; Fundoplication; Gastroplasty; Digestive System Abnormalities; Laparoscopy; Postoperative Complications
PubMed: 37186648
DOI: 10.17116/hirurgia202305131 -
Frontiers in Immunology 2023Inflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by...
INTRODUCTION
Inflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by the nervous system which has evolved to detect inflammatory signals and respond by activating anti-inflammatory processes, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Acute pancreatitis, a common and serious condition without effective therapy, develops when acinar cell injury activates intrapancreatic inflammation. Prior study has shown that electrical stimulation of the carotid sheath, which contains the vagus nerve, boosts the endogenous anti-inflammatory response and ameliorates acute pancreatitis, but it remains unknown whether these anti-inflammatory signals originate in the brain.
METHODS
Here, we used optogenetics to selectively activate efferent vagus nerve fibers originating in the brainstem dorsal motor nucleus of the vagus (DMN) and evaluated the effects on caerulein-induced pancreatitis.
RESULTS
Stimulation of the cholinergic neurons in the DMN significantly attenuates the severity of pancreatitis as indicated by reduced serum amylase, pancreatic cytokines, tissue damage, and edema. Either vagotomy or silencing cholinergic nicotinic receptor signaling by pre-administration of the antagonist mecamylamine abolishes the beneficial effects.
DISCUSSION
These results provide the first evidence that efferent vagus cholinergic neurons residing in the brainstem DMN can inhibit pancreatic inflammation and implicate the cholinergic anti-inflammatory pathway as a potential therapeutic target for acute pancreatitis.
Topics: Humans; Pancreatitis; Acute Disease; Optogenetics; Inflammation; Brain Stem
PubMed: 37180135
DOI: 10.3389/fimmu.2023.1166212 -
Virologica Sinica Jun 2023Erythroleukemia belongs to acute myeloid leukemia (AML) type 6 (M6), and treatment remains difficult due to the poor prognosis of the disease. Friend virus (FV) is a...
Erythroleukemia belongs to acute myeloid leukemia (AML) type 6 (M6), and treatment remains difficult due to the poor prognosis of the disease. Friend virus (FV) is a complex of two viruses: Friend murine leukemia virus (F-MuLV) strain along with a defective spleen focus-forming virus (SFFV), which can induce acute erythroleukemia in mice. We have previously reported that activation of vagal α7 nicotinic acetylcholine receptor (nAChR) signaling promotes HIV-1 transcription. Whether vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain unclear. In this study, sham and vagotomized mice were intraperitoneally injected with FV. FV infection caused anemia in sham mice, and vagotomy reversed this change. FV infection increased erythroblasts ProE, EryA, and EryB cells in the spleen, and these changes were blocked by vagotomy. In bone marrow, FV infection reduced EryC cells in sham mice, an effect that was counteracted by vagotomy. FV infection increased choline acetyltransferase (ChAT) expression in splenic CD4 and CD8 T cells, and this change was reversed by vagotomy. Furthermore, the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4 T cells. In bone marrow, FV infection reduced EryB and EryC cells in sham mice, whereas lack of ChAT in CD4 T cells did not affect this change. Activation of muscarinic acetylcholine receptor 4 (mAChR4) by clozapine N-oxide (CNO) significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected mice. Thus, vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute erythroleukemia. We uncover an unrecognized mechanism of neuromodulation in erythroleukemia.
Topics: Mice; Animals; Leukemia, Erythroblastic, Acute; Friend murine leukemia virus; CD8-Positive T-Lymphocytes; Signal Transduction; Leukemia, Experimental
PubMed: 37172825
DOI: 10.1016/j.virs.2023.05.005 -
The American Surgeon Dec 2023The rate of marginal ulcer (MU) following primary Roux-en-Y Gastric Bypass (RYGB) is approximately .6-16%. Few studies have evaluated recurrence rates following surgical...
INTRODUCTION
The rate of marginal ulcer (MU) following primary Roux-en-Y Gastric Bypass (RYGB) is approximately .6-16%. Few studies have evaluated recurrence rates following surgical revision for MU. The primary aim of this study was to determine the rate of MU recurrence following revision. The secondary aim was to evaluate the impact of truncal vagotomy (TV) on the recurrence rates and analyze potential risk factors associated with the recurrence of MU after revision.
METHODS
We conducted a retrospective cohort study examining data at a single tertiary academic medical center. Adult patients with a history of RYGB who underwent gastrojejunostomy revision for recurrent MU between the years of 2003-2020 were included. We sought to determine our overall rate of MU following revision, with and without TV. Additionally, we examined the association of risk factors with MU recurrence. Fisher's exact test was used to determine the statistical significance of recurrence rates between the groups.
RESULTS
We included 90 patients in the study. The overall recurrence rate for MU was 16.7%. Of the 90 patients, 35 (35.4%) patients underwent TV at the time of revision. The recurrence rate of MU after GJ revision with TV was 14.3% in comparison to those without TV, 18.2% ( = .775). Smoking, steroid, alcohol use, history of cardiac surgery/intervention, and were not significantly associated with recurrent MU following revision.
CONCLUSIONS
The rate of recurrence after revision for MU is high. Adding TV trended towards decreased MU recurrence after revisional surgery, however not significant. Larger studies are needed to evaluate risk factors associated with recurrent MU after revision.
Topics: Adult; Humans; Gastric Bypass; Retrospective Studies; Peptic Ulcer; Vagotomy, Truncal; Reoperation
PubMed: 37167426
DOI: 10.1177/00031348231175134 -
Experimental Neurobiology Apr 2023Subdiaphragmatic vagotomy (SDV) is known to produce analgesic effect in various pain conditions including not only visceral pain but also somatic pain. We aimed to...
Subdiaphragmatic vagotomy (SDV) is known to produce analgesic effect in various pain conditions including not only visceral pain but also somatic pain. We aimed to determine brain mechanisms by which SDV induces analgesic effect in somatic pain condition by using formalin-induced acute inflammatory pain model. We identified brain regions that mediate SDV-induced analgesic effect on acute inflammatory pain by analyzing c-Fos expression in the whole brain. We found that c-Fos expression was specifically increased in the anterior insular cortex (aIC) among subregions of the insular cortex in acute inflammatory pain, which was reversed by SDV. These results were not mimicked in female mice, indicating sexual-dimorphism in SDV-induced analgesia. SDV decreased c-Fos expressions more preferentially in glutamatergic neurons rather than GABAergic neurons in the aIC, and pharmacological activation of glutamatergic neurons with NMDA in the aIC inhibited SDV-induced analgesic effect. Furthermore, chemogenetic activation of glutamatergic neurons in the aIC reversed SDV-induced analgesia. Taken together, our results suggest that the decrease in the neuronal activity of glutamatergic neurons in the aIC mediates SDV-induced analgesic effect, potentially serving as an important therapeutic target to treat inflammatory pain.
PubMed: 37164647
DOI: 10.5607/en23002 -
Frontiers in Neuroscience 2023This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT...
Physiological ischemic training improves cardiac function through the attenuation of cardiomyocyte apoptosis and the activation of the vagus nerve in chronic heart failure.
PURPOSE
This study investigated the functional outcomes of patients with chronic heart failure (CHF) after physiological ischemic training (PIT), identified the optimal PIT protocol, evaluated its cardioprotective effects and explored the underlying neural mechanisms.
METHODS
Patients with CHF were randomly divided into experimental group ( = 25, PIT intervention + regular treatment) and control group ( = 25, regular treatment). The outcomes included the left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP) and cardiopulmonary parameters. LVEF and cardiac biomarkers in CHF rats after various PIT treatments (different in intensity, frequency, and course of treatment) were measured to identify the optimal PIT protocol. The effect of PIT on cardiomyocyte programmed cell death was investigated by western blot, flow cytometry and fluorescent staining. The neural mechanism involved in PIT-induced cardioprotective effect was assessed by stimulation of the vagus nerve and muscarinic M receptor in CHF rats.
RESULTS
LVEF and VOmax increased while BNP decreased in patients subjected to PIT. The optimal PIT protocol in CHF rats was composed of five cycles of 5 min ischemia followed by 5 min reperfusion on remote limbs for 8 weeks. LVEF and cardiac biomarker levels were significantly improved, and cardiomyocyte apoptosis was inhibited. However, these cardioprotective effects disappeared after subjecting CHF rats to vagotomy or muscarinic M receptor inhibition.
CONCLUSION
PIT improved functional outcomes in CHF patients. The optimal PIT protocol required appropriate intensity, reasonable frequency, and adequate treatment course. Under these conditions, improvement of cardiac function in CHF was confirmed through cardiomyocyte apoptosis reduction and vagus nerve activation.
PubMed: 37152604
DOI: 10.3389/fnins.2023.1174455 -
Molecular Psychiatry Jul 2023Chronic stress constitutes a major risk factor for depression that can disrupt various aspects of homeostasis, including the gut microbiome (GM). We have recently shown...
Chronic stress constitutes a major risk factor for depression that can disrupt various aspects of homeostasis, including the gut microbiome (GM). We have recently shown that GM imbalance affects adult hippocampal (HPC) neurogenesis and induces depression-like behaviors, with the exact mechanisms being under active investigation. Here we hypothesized that the vagus nerve (VN), a key bidirectional route of communication between the gut and the brain, could relay the effects of stress-induced GM changes on HPC plasticity and behavior. We used fecal samples derived from mice that sustained unpredictable chronic mild stress (UCMS) to inoculate healthy mice and assess standard behavioral readouts for anxiety- and depressive-like behavior, conduct histological and molecular analyses for adult HPC neurogenesis and evaluate neurotransmission pathways and neuroinflammation. To study the potential role of the VN in mediating the effects of GM changes on brain functions and behavior, we used mice that sustained subdiaphragmatic vagotomy (Vx) prior the GM transfer. We found that inoculation of healthy mice with GM from UCMS mice activates the VN and induces early and sustained changes in both serotonin and dopamine neurotransmission pathways in the brainstem and HPC. These changes are associated with prompt and persistent deficits in adult HPC neurogenesis and induce early and sustained neuroinflammatory responses in the HPC. Remarkably, Vx abrogates adult HPC neurogenesis deficits, neuroinflammation and depressive-like behavior, suggesting that vagal afferent pathways are necessary to drive GM-mediated effects on the brain.
Topics: Mice; Animals; Gastrointestinal Microbiome; Neuroinflammatory Diseases; Brain; Vagus Nerve; Depression; Stress, Psychological
PubMed: 37131071
DOI: 10.1038/s41380-023-02071-6