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Journal of Cerebral Blood Flow and... Aug 2023Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia...
Reversal of the detrimental effects of social isolation on ischemic cerebral injury and stroke-associated pneumonia by inhibiting small intestinal T-cell migration into the brain and lung.
Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia (SAP) remain unclear. Adult male mice were single- or pair-housed with an ovariectomized female mouse and then subjected to transient middle cerebral artery occlusion. Isolated mice were treated with the natriuretic peptide receptor A antagonist A71915 or anti-gamma-delta (γδ) TCR monoclonal antibody, whereas pair-housed mice were treated with recombinant human atrial natriuretic peptide (rhANP). Subdiaphragmatic vagotomy (SDV) was performed 14 days before single- or pair-housed conditions. We found that ISO significantly worsened brain and lung injuries relative to pair housing, which was partially mediated by elevated interleukin (IL)-17A levels and the migration of small intestine-derived inflammatory γδ T-cells into the brain and lung. However, rhANP treatment or SDV could ameliorate ISO-exacerbated post-stroke brain and lung damage by reducing IL-17A levels and inhibiting the migration of inflammatory γδ T-cells into the brain and lung. Our results suggest that rhANP mitigated ISO-induced exacerbation of SAP and ischemic cerebral injury by inhibiting small intestine-derived γδ T-cell migration into the lung and brain, which could be mediated by the subdiaphragmatic vagus nerve.
Topics: Male; Female; Mice; Humans; Animals; T-Lymphocytes; Brain; Stroke; Pneumonia; Lung; Intestine, Small; Social Isolation; Cell Movement; Mice, Inbred C57BL
PubMed: 37017434
DOI: 10.1177/0271678X231167946 -
Digestive Surgery 2016Vagus nerve injury (VNI) is a feared complication of antireflux surgery (ARS). The impact of VNI on the functional outcomes of ARS has not yet been evaluated... (Review)
Review
BACKGROUND
Vagus nerve injury (VNI) is a feared complication of antireflux surgery (ARS). The impact of VNI on the functional outcomes of ARS has not yet been evaluated systematically. The aim of this review was to evaluate the impact of VNI on functional and clinical outcome of ARS.
METHODS
A systematic search was performed until March 2015, using the following online databases: MEDLINE, Embase and the Cochrane Register of Controlled Clinical Trials. Eight studies remained available for assessment. Articles were divided into 2 groups: (a) one with unintended, accidental VNI and (b) one group comparing ARS with and without intended vagotomy.
RESULTS
The prevalence of unintended, accidental VNI ranged from 10 to 42% after ARS. No clear differences were seen in outcome for reflux control between the VNI and vagus nerve intact group. A higher prevalence of diarrhea, nausea and vomiting was observed in the VNI group.
CONCLUSION
VNI is a feared but neglected complication of ARS. Larger prospective studies that objectively assess vagus nerve integrity before and after ARS are needed.
Topics: Diarrhea; Gastric Emptying; Gastroesophageal Reflux; Humans; Nausea; Postoperative Complications; Prevalence; Treatment Outcome; Vagotomy; Vagus Nerve Injuries; Vomiting
PubMed: 26990200
DOI: 10.1159/000444147 -
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 -
Iranian Journal of Medical Sciences Jul 2020Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory...
BACKGROUND
Pulmonary dysfunction is one of the critical complications of a stroke. However, it remains unclear whether the mechanism is caused by either neurogenic or inflammatory reactions. The present study aimed to determine the effect of cerebral ischemia-reperfusion injury and the role of the vagus nerve on hypoxic pulmonary vasoconstriction (HPV) in rats.
METHODS
This study was performed at Shiraz University of Medical Sciences, Shiraz, Iran, 2018. Male Sprague Dawley rats (n=56) were divided into four groups, namely the sham, vagotomy (Vag), 1 hour of ischemia followed by 23 hours of reperfusion without vagotomy (I/R) and with vagotomy (I/R+Vag). Neurological deficit scores and total infarct volumes of brains were measured in the I/R and I/R+Vag groups. Pulmonary artery pressure and lung weight were continuously registered during ventilation with normoxic and hypoxic gases in the isolated lungs. The blood gas parameters and the lung malondialdehyde (MDA) level of each group were also evaluated. ANOVA, with Tukey's test and test, was used to compare the variables in the experimental groups.
RESULTS
The infarct volume of the brains in the I/R and I/R+Vag groups were similar. HPV in the I/R group was lower than those in the sham and Vag groups, while vagotomy reversed this response in the I/R+Vag group (P=0.004). In the I/R group, PO and pH were lower, and PCO was higher than those in the sham and Vag groups. The lung MDA level in the I/R group was higher than that in the Vag group (P=0.019).
CONCLUSION
Brain ischemia-reperfusion injury decreased HPV independent of increased MDA in the lung, whereas vagotomy improved HPV by repairing the blood-gas barrier and oxygen sensing.
PubMed: 32801414
DOI: 10.30476/IJMS.2019.45789 -
International Journal of Molecular... Aug 2022TBI induces splenic B and T cell expansion that contributes to neuroinflammation and neurodegeneration. The vagus nerve, the longest of the cranial nerves, is the...
TBI induces splenic B and T cell expansion that contributes to neuroinflammation and neurodegeneration. The vagus nerve, the longest of the cranial nerves, is the predominant parasympathetic pathway allowing the central nervous system (CNS) control over peripheral organs, including regulation of inflammatory responses. One way this is accomplished is by vagus innervation of the celiac ganglion, from which the splenic nerve innervates the spleen. This splenic innervation enables modulation of the splenic immune response, including splenocyte selection, activation, and downstream signaling. Considering that the left and right vagus nerves have distinct courses, it is possible that they differentially influence the splenic immune response following a CNS injury. To test this possibility, immune cell subsets were profiled and quantified following either a left or a right unilateral vagotomy. Both unilateral vagotomies caused similar effects with respect to the percentage of B cells and in the decreased percentage of macrophages and T cells following vagotomy. We next tested the hypothesis that a left unilateral vagotomy would modulate the splenic immune response to a traumatic brain injury (TBI). Mice received a left cervical vagotomy or a sham vagotomy 3 days prior to a fluid percussion injury (FPI), a well-characterized mouse model of TBI that consistently elicits an immune and neuroimmune response. Flow cytometric analysis showed that vagotomy prior to FPI resulted in fewer CLIP+ B cells, and CD4+, CD25+, and CD8+ T cells. Vagotomy followed by FPI also resulted in an altered distribution of CD11b and CD11b macrophages. Thus, transduction of immune signals from the CNS to the periphery via the vagus nerve can be targeted to modulate the immune response following TBI.
Topics: Animals; Brain Injuries, Traumatic; Disease Models, Animal; Mice; Spleen; Vagotomy; Vagus Nerve
PubMed: 36077246
DOI: 10.3390/ijms23179851 -
Reproductive Biology and Endocrinology... Jun 2022Women with endometriosis have been shown to have a reduced vagal tone as compared with controls and vagotomy promoted while vagus nerve stimulation (VNS) decelerated the...
BACKGROUND
Women with endometriosis have been shown to have a reduced vagal tone as compared with controls and vagotomy promoted while vagus nerve stimulation (VNS) decelerated the progression of endometriosis in mice. Extensive research also has shown that the activation of the cholinergic anti-inflammatory pathway by VNS activates α7 nicotinic acetylcholine receptor (α7nAChR), potently reducing inflammation. Yet whether α7nAChR plays any role in endometriosis is unknown. We evaluated its expression in normal endometrium, ovarian and deep endometriotic lesions, and evaluated its role in the development of endometriosis.
METHODS
Immunohistochemistry analyses of α7nAChR in endometriotic lesions as well as control endometrium, and quantification of tissue fibrosis by Masson trichrome staining were performed. Mouse experiments were conducted to evaluate the impact of α7nAChR activation or suppression on lesional progression and possible therapeutic effect. Finally, in vitro experiments were conducted to evaluate the effect of activation of α7nAChR on epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM) and fibrogenesis in an endometriotic epithelial cell line and primary endometriotic stromal cells derived from ovarian endometrioma tissue samples.
RESULTS
Immunostaining of α7nAChR was significantly reduced in human endometriotic epithelial cells as compared with their counterpart in normal endometrium. Lesional α7nAChR staining levels correlated negatively with lesional fibrosis and the severity of dysmenorrhea. The α7nAChR agonist significantly impeded the development of endometriotic lesions in mouse models possibly through hindrance of EMT and FMT. It also demonstrated therapeutic effects in mice with induced deep endometriosis. Treatment of endometriotic epithelial and stromal cells with an α7nAChR agonist significantly abrogated platelet-induced EMT, FMT and SMM, and suppressed cellular contractility and collagen production.
CONCLUSIONS
α7nAChR is suppressed in endometriotic lesions, and its activation by pharmacological means can impede EMT, FMT, SMM, and fibrogenesis of endometriotic lesions. As such, α7nAChR can be rightfully viewed as a potential target for therapeutic invention.
TRIAL REGISTRATION
Not applicable.
Topics: Animals; Cell Transdifferentiation; Endometriosis; Female; Fibrosis; Humans; Mice; Myofibroblasts; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35658970
DOI: 10.1186/s12958-022-00955-w -
BioRxiv : the Preprint Server For... Sep 2023Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the...
Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut to brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of the gut mucosa express α-synuclein. In this study, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from gut epithelial cells in organoids co-cultured with vagal nodose neurons that are otherwise devoid of α-synuclein expression. In intact mice that express pathological human α-synuclein, but no mouse α-synuclein, α-synuclein fibril templating activity emerges in α-synuclein seeded fibril aggregation assays in tissues from the gut, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfers to the vagus nerve and to the dorsal motor nucleus. Subdiaphragmatic vagotomy prior to the induction of α-synuclein expression in the gut epithelial cells effectively protects the hindbrain from the emergence of α-synuclein fibril templating activity. Overall, these findings highlight a novel potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells.
PubMed: 37645945
DOI: 10.1101/2023.08.14.553305 -
Arquivos Brasileiros de Cirurgia... 2021Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the...
BACKGROUND
Gastrointestinal disorders are frequently reported in patients with Parkinson's disease whose disorders reduce the absorption of nutrients and drugs, worsening the clinical condition of patients. However, the mechanisms involved in modifying gastrointestinal pathophysiology have not yet been fully explained.
AIM
To evaluate its effects on gastrointestinal motility and the involvement of the vagal and splanchnic pathways.
METHODS
Male Wistar rats (250-300 g, n = 84) were used and divided into two groups. Group I (6-OHDA) received an intrastriatal injection of 6-hydroxydopamine (21 µg/animal). Group II (control) received a saline solution (NaCl, 0.9%) under the same conditions. The study of gastric emptying, intestinal transit, gastric compliance and operations (vagotomy and splanchnotomy) were performed 14 days after inducing neurodegeneration. Test meal (phenol red 5% glucose) was used to assess the rate of gastric emptying and intestinal transit.
RESULTS
Parkinson's disease delayed gastric emptying and intestinal transit at all time periods studied; however, changes in gastric compliance were not observed. The delay in gastric emptying was reversed by pretreatment with vagotomy and splanchnotomy+celiac gangliectomy, thus suggesting the involvement of such pathways in the observed motor disorders.
CONCLUSION
Parkinson's disease compromises gastric emptying, as well as intestinal transit, but does not alter gastric compliance. The delay in gastric emptying was reversed by truncal vagotomy, splanchnotomy and celiac ganglionectomy, suggesting the involvement of such pathways in delaying gastric emptying.
Topics: Animals; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Male; Parkinson Disease; Rats; Rats, Wistar; Vagotomy
PubMed: 33470378
DOI: 10.1590/0102-672020200003e1548 -
Journal of Oncology 2018This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the... (Review)
Review
This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the relationship between heart rate variability, the main vagus nerve index, and prognosis in cancer patients (survival and tumor markers). These studies show that initially high vagal nerve activity predicts better cancer prognosis, and, in some studies, independent of confounders such as cancer stage and treatments. Since the design of the epidemiological studies is correlational, any causal relationship between heart rate variability and cancer prognosis cannot be inferred. However, various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship. The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth, while vagal nerve activation improves cancer prognosis. Based on all reviewed studies, it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage.
PubMed: 30057605
DOI: 10.1155/2018/1236787 -
Neurobiology of Disease Jan 2023Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination...
Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling that of patients with MS. Given the role of the vagus nerve in gut-microbiota-brain axis in development of MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects demyelination in CPZ-treated mice. SDV significantly ameliorated demyelination and microglial activation in the brain compared with sham-operated CPZ-treated mice. Furthermore, 16S ribosomal RNA analysis revealed that SDV significantly improved the abnormal gut microbiota composition of CPZ-treated mice. An untargeted metabolomic analysis demonstrated that SDV significantly improved abnormal blood levels of metabolites in CPZ-treated mice compared with sham-operated CPZ-treated mice. Notably, there were correlations between demyelination or microglial activation in the brain and the relative abundance of several microbiome populations, suggesting a link between gut microbiota and the brain. There were also correlations between demyelination or microglial activation in the brain and blood levels of metabolites. Together, these data suggest that CPZ produces demyelination in the brain through the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve.
Topics: Animals; Mice; Brain; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Mice, Inbred C57BL; Microbiota; Microglia; Multiple Sclerosis; Vagus Nerve
PubMed: 36493975
DOI: 10.1016/j.nbd.2022.105951