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Alimentary Pharmacology & Therapeutics Jun 2020The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties.
BACKGROUND
The vagus nerve provides essential parasympathetic innervation to the gastrointestinal system and is known to have anti-inflammatory properties.
AIMS
To explore the relationship between vagotomy and the risk of inflammatory bowel disease (IBD) and its major categories: Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
A matched cohort comprising 15 637 patients undergoing vagotomy was identified through the Swedish Patient Register from 1964 to 2010. Each vagotomised patient was matched for birth year and gender with 40 nonvagotomised individuals on the date of vagotomy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for IBD using flexible parametric models adjusted for matching variables, year of vagotomy, birth country, chronic obstructive pulmonary disease and comorbidity index.
RESULTS
We observed 119 (0.8%) patients with vagotomy developed IBD compared to 3377 (0.5%) IBD cases in nonvagotomised individuals. The crude incidence of IBD (per 1000 person-years) was 0.38 for vagotomised patients and 0.25 for nonvagotomised individuals. We observed a time-dependent elevated risk of IBD associated with vagotomy, for instance, the HR (95% CI) was 1.80 (1.40-2.31) at year 5 and 1.49 (1.14-1.96) at year 10 post-vagotomy. The association appeared to be stronger for truncal than selective vagotomy and limited to CD (HR was 3.63 [1.94-6.80] for truncal and 2.06 [1.49-2.84] for selective vagotomy) but not UC (1.36 [0.71-2.62] for truncal and 1.25 [0.95-1.63] for selective vagotomy).
CONCLUSIONS
We found a positive association between vagotomy and later IBD, particularly for CD. The finding indirectly underlines the beneficial role of the vagal tone in IBD.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cohort Studies; Colitis, Ulcerative; Crohn Disease; Female; Humans; Incidence; Inflammatory Bowel Diseases; Male; Middle Aged; Postoperative Complications; Registries; Risk Factors; Sweden; Vagotomy
PubMed: 32319125
DOI: 10.1111/apt.15715 -
BioRxiv : the Preprint Server For... Dec 2023Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous/desynchronous signals are transmitted among tissues is...
UNLABELLED
Circadian desynchrony induced by shiftwork or jetlag is detrimental to metabolic health, but how synchronous/desynchronous signals are transmitted among tissues is unknown. Here we report that liver molecular clock dysfunction is signaled to the brain via the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a previously unrecognized homeostatic feedback signal that relies on synchrony between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a therapeutic target for obesity in the setting of chrono-disruption.
ONE SENTENCE SUMMARY
The hepatic vagal afferent nerve signals internal circadian desynchrony between the brain and liver to induce maladaptive food intake patterns.
PubMed: 38077098
DOI: 10.1101/2023.11.30.568080 -
Life Sciences Feb 2023The neuropathology of Parkinson's disease (PD) is complex and affects multiple systems of the body beyond the central nervous system. This study examined the effects of...
The effects of gallic acid and vagotomy on motor function, intestinal transit, brain electrophysiology and oxidative stress alterations in a rat model of Parkinson's disease induced by rotenone.
INTRODUCTION
The neuropathology of Parkinson's disease (PD) is complex and affects multiple systems of the body beyond the central nervous system. This study examined the effects of gallic acid (GA) and gastrointestinal vagotomy (VG) on motor, cognitive, intestinal transit time, and thalamic nuclei electrical power in an animal model of PD induced by rotenone.
MATERIALS AND METHODS
Male Wistar rats were divided into 4 groups: Sham, ROT, ROT+GA, VG + ROT. Sham rats received vehicle, those in ROT received rotenone (5 mg/kg/2 ml, ig), PD rats in ROT+GA were treated with GA (100 mg/kg, gavage/once daily, for 28 days), and in VG + ROT, the vagal nerve was dissected. Stride length, motor coordination and locomotion, intestinal transit time, cognitive and pain threshold, and thalamic local EEG were evaluated. Oxidative stress indexes in striatal tissue were also measured.
RESULTS
Rotenone diminished significantly the stride length (p < 0.001), motor coordination (p < 0.001), power of thalamic EEG (p < 0.01) and pain (p < 0.001). MDA increased significantly (p < 0.001) while GPx activity decreased (p < 0.001). Intestinal transit time rose significantly (p < 0.01). PD rats treated with GA improved all above disorders (p < 0.001, p < 0.01). Vagotomy prevented significant alterations of motor and non-motor parameters by rotenone.
CONCLUSION
According to current findings, rotenone acts as a toxin in GI and plays a role in the pathogenesis of PD through gastric vagal nerve. Thus, vagotomy could prevent the severity of toxicity by rotenone. In addition, GA improved symptoms of PD induced by rotenone. Therefore, GA can be regarded as a promising therapeutic candidate for PD patients.
Topics: Rats; Male; Animals; Rotenone; Gallic Acid; Rats, Wistar; Parkinson Disease; Oxidative Stress; Brain; Vagotomy; Electrophysiology; Neuroprotective Agents; Disease Models, Animal
PubMed: 36621537
DOI: 10.1016/j.lfs.2022.121356 -
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 -
European Journal of Pharmacology Dec 2021Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However,...
Disruption in the nerve-tumor interaction is now considered as a possible anticancer strategy for treating various cancer types, particularly colorectal cancer. However, the underlying mechanisms are not still fully understood. Therefore, the present study aimed to evaluate the effects of sympathetic and parasympathetic denervation on the inhibition of colorectal cancer progression in early and late phases and assess the involvement of nerve growth factor in denervation mediated anticancer effects. One-hundred and fifty male Wistar rats were assigned into 15 groups. Seven groups comprising the control group, 1,2-dimethylhydrazine (DMH) group, sympathetic denervation group (celiac-mesenteric ganglionectomy and guanethidine sulphate administration), parasympathetic denervation group (vagotomy and atropine administration), and combination group were used in the early-stage protocol. For the late-stage protocol, eight groups comprising the control, DMH, surgical and pharmacological sympathetic and parasympathetic denervation groups, combination group, and 5-flourouracil group were considered. After 8 weeks, sympathetic and parasympathetic denervation significantly reduced ACF numbers in rats receiving DMH. On the other hand, in the late stages, parasympathetic but not sympathetic denervation resulted in significant reductions in tumor incidence, tumor volume and weight, cell proliferation (indicated by reduced immunostaining of PCNA and ki-67), and angiogenesis (indicated by reduced immunostaining of CD31 and VEGF expression levels), and downregulated NGF, β2 adrenergic, and M3 receptors. It can be concluded that parasympathetic denervation may be of high importance in colon carcinogenesis and suggested as a possible therapeutic modality in late stages of colorectal cancer.
Topics: 1,2-Dimethylhydrazine; Animals; Atropine; Carcinogenesis; Carcinogens; Colon; Colorectal Neoplasms; Disease Progression; Ganglia, Sympathetic; Ganglionectomy; Guanethidine; Humans; Male; Mesentery; Neoplasms, Experimental; Parasympathetic Nervous System; Rats; Rats, Wistar; Vagotomy
PubMed: 34774852
DOI: 10.1016/j.ejphar.2021.174626 -
IEEE Transactions on Ultrasonics,... Feb 2024Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been...
Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1β ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.
Topics: Mice; Animals; Lipopolysaccharides; Vagus Nerve; Heart; Cytokines; Heart Diseases
PubMed: 38064323
DOI: 10.1109/TUFFC.2023.3341248 -
Frontiers in Medicine 2022Clinical-experimental considerations and an approach to understanding the autonomic basis of improved surgical outcomes using Perioperative Music Medicine (PMM) are... (Review)
Review
Clinical-experimental considerations and an approach to understanding the autonomic basis of improved surgical outcomes using Perioperative Music Medicine (PMM) are reviewed. Combined surgical, psycho-physiological, and experimental perspectives on Music Medicine (MM) and its relationship to autonomic nervous system (ANS) function are discussed. Considerations are given to the inter-related perioperative effects of MM on ANS, pain, and underlying vagal and other neural circuits involved in emotional regulation and dysregulation. Many surgical procedures are associated with significant pain, which is routinely treated with post-operative opioid medications, which cause detrimental side effects and delay recovery. Surgical trauma shifts the sympathetic ANS to a sustained activation impairing physiological homeostasis and causing psychological stress, as well as metabolic and immune dysfunction that contribute to postoperative mortality and morbidity. In this article, we propose a plan to operationalize the study of mechanisms mediating the effects of MM in perioperative settings of orthopedic surgery. These studies will be critical for the implementation of PMM as a routine clinical practice and to determine the potential limitations of MM in specific cohorts of patients and how to improve the treatment.
PubMed: 35187004
DOI: 10.3389/fmed.2022.821022 -
NPJ Parkinson's Disease Mar 2022Parkinson's disease (PD) may optimally be treated with a disease-modifying therapy to slow progression. We compare data underlying surgical approaches proposed to impart... (Review)
Review
Parkinson's disease (PD) may optimally be treated with a disease-modifying therapy to slow progression. We compare data underlying surgical approaches proposed to impart disease modification in PD: (1) cell transplantation therapy with stem cell-derived dopaminergic neurons to replace damaged cells; (2) clinical trials of growth factors to promote survival of existing dopaminergic neurons; (3) subthalamic nucleus deep brain stimulation early in the course of PD; and (4) abdominal vagotomy to lower risk of potential disease spread from gut to brain. Though targeted to engage potential mechanisms of PD these surgical approaches remain experimental, indicating the difficulty in translating therapeutic concepts into clinical practice. The choice of outcome measures to assess disease modification separate from the symptomatic benefit will be critical to evaluate the effect of the disease-modifying intervention on long-term disease burden, including imaging studies and clinical rating scales, i.e., Unified Parkinson Disease Rating Scale. Therapeutic interventions will require long follow-up times (i.e., 5-10 years) to analyze disease modification compared to symptomatic treatments. The promise of invasive, surgical treatments to achieve disease modification through mechanistic approaches has been constrained by the reality of translating these concepts into effective clinical trials.
PubMed: 35338165
DOI: 10.1038/s41531-022-00296-w -
Biotechnic & Histochemistry : Official... Feb 2022Gastric outlet obstruction (GOO) is caused mainly by pyloric or duodenal blockage; gastric surgery and vagotomy are effective treatments. We investigated the short term...
Gastric outlet obstruction (GOO) is caused mainly by pyloric or duodenal blockage; gastric surgery and vagotomy are effective treatments. We investigated the short term effects of experimental GOO and truncal vagotomy (TV) on gut hormone levels. We used 8-week-old male Wistar rats divided randomly into four groups: control, GOO, TV, and GOO + TV. At the end of the experiment, blood and tissue samples of the pylorus and fundus were obtained for biochemical and immunohistochemical analysis. Gastric motility decreased in the TV group, but there was no difference in food intake compared to the control group; water consumption and urine output were increased. Feces excretion and food intake decreased due to loss of food movement from the stomach of GOO and GOO + TV rats. Levels of insulin and ghrelin were lower than for the control group, but levels of cholecystokinin were higher. Leptin and glucagon-like peptide 1 levels were increased in the GOO group, while somatostatin was decreased. Leptin immunostaining levels were decreased in the GOO + TV group. Gastrin and neuropeptide Y levels were lower in the GOO and GOO + TV groups compared to the other groups. We found that both gut hormone levels related to gastric motility and metabolism, and immunohistochemical staining of the stomach tissue were altered by TV and GOO. Measuring changes in gut hormones following gastric surgery could be useful for monitoring the effectiveness of treatment.
Topics: Animals; Gastric Outlet Obstruction; Male; Rats; Rats, Wistar; Vagotomy, Truncal
PubMed: 33722110
DOI: 10.1080/10520295.2021.1896780 -
Brain Sciences Feb 2023Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the...
Auricular Vagus Nerve Stimulation Improves Visceral Hypersensitivity and Gastric Motility and Depression-like Behaviors via Vago-Vagal Pathway in a Rat Model of Functional Dyspepsia.
UNLABELLED
Transcutaneous auricular vagus nerve stimulation was recently reported to have a therapeutic potential for functional dyspepsia (FD). This study aimed to explore the integrative effects and mechanisms of auricular vagus nerve stimulation (aVNS) in a rodent model of FD.
METHODS
We evaluated the effects of aVNS on visceral hypersensitivity, gastric motility and open field test (OFT) activity in iodoacetamide (IA)-treated rats. The autonomic function was assessed; blood samples and tissues were collected and analyzed by an enzyme-linked immunosorbent assay and western blot. Vagotomy was performed to investigate the role of vagal efferent nerve.
RESULTS
aVNS reduced the electromyography response to gastric distension, improved gastric emptying and increased the horizontal and vertical motion scores of the OFT in IA-treated rats. The sympathovagal ratio was increased in IA-treated rats but normalized with aVNS. The serum cytokines TNF-α, IL-6, IL-1β and NF-κBp65 were increased in IA-treated rats and decreased with aVNS. The hypothalamus-pituitary-adrenal axis was hyperactive in IA-treated rats but inhibited by aVNS. The expression of duodenal desmoglein 2 and occludin were all decreased in IA-treated rats and increased with aVNS but not sham-aVNS. Vagotomy abolished the ameliorating effects of aVNS on gastric emptying, horizontal motions, serum TNF-α and duodenal NF-κBp65.
CONCLUSION
aVNS improves gastric motility and gastric hypersensitivity probably by anti-inflammatory mechanisms via the vago-vagal pathways. A better understanding on the mechanisms of action involved with aVNS would lead to the optimization of the taVNS methodology and promote taVNS as a non-pharmacological alternative therapy for FD.
PubMed: 36831796
DOI: 10.3390/brainsci13020253