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Acta Neurobiologiae Experimentalis 2023In the central nervous system, long‑term effects of a vagotomy include disturbance of monoaminergic activity of the limbic system. Since low vagal activity is observed...
In the central nervous system, long‑term effects of a vagotomy include disturbance of monoaminergic activity of the limbic system. Since low vagal activity is observed in major depression and autism spectrum disorder, the study aimed to determine whether animals fully recovered after subdiaphragmatic vagotomy demonstrates neurochemical indicators of altered well‑being and social component of sickness behavior. Bilateral vagotomy or sham surgery was performed in adult rats. After one month of recovery, rats were challenged with lipopolysaccharide or vehicle to determine the role of central signaling upon sickness. Striatal monoamines and met‑enkephalin concentrations were evaluated using HPLC and RIA methods. We also defined a concentration of immune‑derived plasma met‑enkephalin to establish a long‑term effect of vagotomy on peripheral analgesic mechanisms. The data indicate that 30 days after vagotomy procedure, striatal dopaminergic, serotoninergic, and enkephalinergic neurochemistry was altered, both under physiological and inflammatory conditions. Vagotomy prevented inflammation‑induced increases of plasma met‑enkephalin - an opioid analgesic. Our data suggest that in a long perspective, vagotomized rats may be more sensitive to pain and social stimuli during peripheral inflammation.
Topics: Rats; Animals; Enkephalin, Methionine; Autism Spectrum Disorder; Vagotomy; Vagus Nerve; Inflammation; Amines
PubMed: 37078817
DOI: 10.55782/ane-2023-009 -
The Journal of Physiology May 2023Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of...
Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of myocardial hypoxia, but the relative contribution of these two mechanisms and how this balance changes with evolving fetal compromise remain unknown. In the present study, chronically instrumented near-term fetal sheep received surgical vagotomy (n = 8) or sham vagotomy (control, n = 11) to disable the peripheral chemoreflex and unmask myocardial hypoxia. One-minute complete umbilical cord occlusions (UCOs) were performed every 2.5 min for 4 h or until arterial pressure fell below 20 mmHg. Hypotension and severe acidaemia developed progressively after 65.7 ± 7.2 UCOs in control fetuses and 49.5 ± 7.8 UCOs after vagotomy. Vagotomy was associated with faster development of metabolic acidaemia and faster impairment of arterial pressure during UCOs without impairing centralization of blood flow or neurophysiological adaptation to UCOs. During the first half of the UCO series, before severe hypotension developed, vagotomy was associated with a marked increase in FHR during UCOs. After the onset of evolving severe hypotension, FHR fell faster in control fetuses during the first 20 s of UCOs, but FHR during the final 40 s of UCOs became progressively more similar between groups, with no difference in the nadir of decelerations. In conclusion, FHR decelerations were initiated and sustained by the peripheral chemoreflex at a time when fetuses were able to maintain arterial pressure. After the onset of evolving hypotension and acidaemia, the peripheral chemoreflex continued to initiate decelerations, but myocardial hypoxia became progressively more important in sustaining and deepening decelerations. KEY POINTS: Brief repeated hypoxaemia during labour can trigger fetal heart rate decelerations by either the peripheral chemoreflex or myocardial hypoxia, but how this balance changes with fetal compromise is unknown. Reflex control of fetal heart rate was disabled by vagotomy to unmask the effects of myocardial hypoxia in chronically instrumented fetal sheep. Fetuses were then subjected to repeated brief hypoxaemia consistent with the rates of uterine contractions during labour. We show that the peripheral chemoreflex controls brief decelerations in their entirety at a time when fetuses were able to maintain normal or increased arterial pressure. The peripheral chemoreflex still initiated decelerations even after the onset of evolving hypotension and acidaemia, but myocardial hypoxia made an increasing contribution to sustain and deepen decelerations.
Topics: Female; Sheep; Pregnancy; Animals; Humans; Deceleration; Heart Rate, Fetal; Umbilical Cord; Fetus; Hypoxia; Myocardial Ischemia; Acidosis; Hypotension; Fetal Hypoxia
PubMed: 37017488
DOI: 10.1113/JP284286 -
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 -
Bioelectronic Medicine Mar 2023The liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may...
BACKGROUND
The liver is an important immunological organ and liver inflammation is part of the pathophysiology of non-alcoholic steatohepatitis, a condition that may promote cirrhosis, liver cancer, liver failure, and cardiovascular disease. Despite dense innervation of the liver parenchyma, little is known about neural regulation of liver function in inflammation. Here, we study vagus nerve control of the liver response to acute inflammation.
METHODS
Male C57BL/6 J mice were subjected to either sham surgery, surgical vagotomy, or electrical vagus nerve stimulation followed by intraperitoneal injection of the TLR2 agonist zymosan. Animals were euthanized and tissues collected 12 h after injection. Samples were analyzed by qPCR, RNAseq, flow cytometry, or ELISA.
RESULTS
Hepatic mRNA levels of pro-inflammatory mediators Ccl2, Il-1β, and Tnf-α were significantly higher in vagotomized mice compared with mice subjected to sham surgery. Differences in liver Ccl2 levels between treatment groups were largely reflected in the plasma chemokine (C-C motif) ligand 2 (CCL2) concentration. In line with this, we observed a higher number of macrophages in the livers of vagotomized mice compared with sham as measured by flow cytometry. In mice subjected to electrical vagus nerve stimulation, hepatic mRNA levels of Ccl2, Il1β, and Tnf-α, and plasma CCL2 levels, were significantly lower compared with sham. Interestingly, RNAseq revealed that a key activation marker for hepatic stellate cells (HSC), Pnpla3, was the most significantly differentially expressed gene between vagotomized and sham mice. Of note, several HSC-activation associated transcripts were higher in vagotomized mice, suggesting that signals in the vagus nerve contribute to HSC activation. In support of this, we observed significantly higher number of activated HSCs in vagotomized mice as compared with sham as measured by flow cytometry.
CONCLUSIONS
Signals in the cervical vagus nerve controlled hepatic inflammation and markers of HSC activation in zymosan-induced peritonitis.
PubMed: 36997988
DOI: 10.1186/s42234-023-00108-3 -
Biomedicine & Pharmacotherapy =... Jun 2023Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on...
PURPOSE
Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms.
METHODS
Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint "Neiguan (PC6)" was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages.
RESULTS
EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy.
CONCLUSION
EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.
Topics: Rats; Animals; Rats, Sprague-Dawley; alpha7 Nicotinic Acetylcholine Receptor; Electroacupuncture; Vagus Nerve; Inflammation; Heart Diseases; Punctures; Cecum; Sepsis
PubMed: 36996679
DOI: 10.1016/j.biopha.2023.114600 -
Annals of Medicine and Surgery (2012) Mar 2023Gastrojejunocolic fistula (GJF) is an infrequent condition that presents late as a complication of gastroenterostomy conducted for complications of peptic ulcer disease...
UNLABELLED
Gastrojejunocolic fistula (GJF) is an infrequent condition that presents late as a complication of gastroenterostomy conducted for complications of peptic ulcer disease and is believed to be a result of continuous acid secretion due to insufficient stomach resection and incomplete vagotomy. Symptoms of the fistula present late, usually 20 years or more after gastroenterostomy. Patients with GJF usually present with chronic on-and-off diarrhea, weight loss, fecal-smelling belching or vomiting, and malnutrition.
CASE PRESENTATION
The case is of a 45-year-old man with GJF who presented with diarrhea, weight loss, and foul-smelling vomiting. The diagnosis was made intraoperatively despite preoperative investigations with computerized tomography scan and endoscopy. The patient underwent a single-stage operation, and the postoperative course was uneventful.
CONCLUSION
Knowledge of this uncommon illness can aid in prevention through improved operative strategy and medical treatment during the stomal ulcer phase with proton pump inhibitor and eradication.
PubMed: 36923760
DOI: 10.1097/MS9.0000000000000128 -
American Journal of Clinical and... 2023The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became...
BACKGROUND
The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet.
METHODS
In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated.
RESULTS
Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression.
CONCLUSION
The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes.
PubMed: 36923727
DOI: No ID Found -
Brain Stimulation 2023Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's...
Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway.
BACKGROUND
Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined.
OBJECTIVE
To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats.
METHODS
Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively.
RESULTS
Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects.
CONCLUSION
Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.
Topics: Rats; Animals; Parkinson Disease; Vagus Nerve Stimulation; Vagus Nerve; Afferent Pathways; Anti-Inflammatory Agents
PubMed: 36914065
DOI: 10.1016/j.brs.2023.03.003 -
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 -
Journal of Cardiovascular Development... Jan 2023Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary...
Sympathetic Denervation and Pharmacological Stimulation of Parasympathetic Nervous System Prevent Pulmonary Vascular Bed Remodeling in Rat Model of Chronic Thromboembolic Pulmonary Hypertension.
Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.
PubMed: 36826536
DOI: 10.3390/jcdd10020040