RESUMEN
The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.
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Cognición , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Gerbillinae , Nervio Vago , Animales , Nervio Vago/metabolismo , Masculino , Accidente Cerebrovascular Isquémico/metabolismo , Dieta Alta en Grasa/efectos adversos , Eje Cerebro-Intestino/fisiología , Vagotomía , Hipocampo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismoRESUMEN
The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone.
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Motilidad Gastrointestinal , Corteza Insular , Yeyuno , Animales , Masculino , Yeyuno/fisiología , Motilidad Gastrointestinal/fisiología , Corteza Insular/fisiología , Vagotomía , Ratas , Ingestión de Alimentos/fisiología , Ratas Sprague-DawleyRESUMEN
Unacylated ghrelin (UAG), the unacylated form of ghrelin, accounts for 80%-90% of its circulation. Accumulated studies have pointed out that UAG may be used to treat metabolic disorders. This study aimed to investigate the effect of intestinal perfusion of UAG on metabolically associated fatty liver disease (MAFLD) induced by a high-fat diet and its possible mechanisms. Neuronal retrograde tracking combined with immunofluorescence, central administration of a glucagon-like peptide-1 receptor (GLP-1R) antagonist, and hepatic vagotomy was performed to reveal its possible mechanism involving a central glucagon-like peptide-1 (GLP-1) pathway. The results showed that intestinal perfusion of UAG significantly reduced serum lipids, aminotransferases, and food intake in MAFLD rats. Steatosis and lipid accumulation in the liver were significantly alleviated, and lipid metabolism-related enzymes in the liver were regulated. UAG upregulated the expression of GLP-1 receptor (GLP-1R) in the paraventricular nucleus (PVN) and GLP-1 in the nucleus tractus solitarii (NTS), as well as activated GLP-1 neurons in the NTS. Furthermore, GLP-1 fibers projected from NTS to PVN were activated by the intestinal perfusion of UAG. However, hepatic vagotomy and GLP-1R antagonists delivered into PVN before intestinal perfusion of UAG partially attenuated its alleviation of MAFLD. In conclusion, intestinal perfusion of UAG showed a therapeutic effect on MAFLD, which might be related to its activation of the GLP-1 neuronal pathway from NTS to PVN. The present results provide a new strategy for the treatment of MAFLD.NEW & NOTEWORTHY Intestinal perfusion of UAG, the unacylated form of ghrelin, has shown promising potential for treating MAFLD. This study unveils a potential mechanism involving the central GLP-1 pathway, with UAG upregulating GLP-1R expression and activating GLP-1 neurons in specific brain regions. These findings propose a novel therapeutic strategy for MAFLD treatment through UAG and its modulation of the GLP-1 neuronal pathway.
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Ghrelina , Péptido 1 Similar al Glucagón , Receptor del Péptido 1 Similar al Glucagón , Animales , Ghrelina/metabolismo , Ghrelina/farmacología , Masculino , Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Dieta Alta en Grasa , Metabolismo de los Lípidos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Perfusión/métodos , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , VagotomíaRESUMEN
The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines-including IL-6, IL-1ß, and TNF-α-in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy's beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy's protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities.
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Ansiedad , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Vagotomía , Nervio Vago , Ácido gamma-Aminobutírico , Animales , Ansiedad/metabolismo , Ratones , Nervio Vago/metabolismo , Masculino , Ácido gamma-Aminobutírico/metabolismo , Salmonella typhimurium , Citocinas/metabolismo , Eje Cerebro-Intestino , Encéfalo/metabolismo , Infecciones por Salmonella/metabolismo , Conducta Animal , Hipocampo/metabolismo , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Inflamación/metabolismo , Amígdala del Cerebelo/metabolismoRESUMEN
Viscerosensory information travels to the brain via vagal afferents, where it is first integrated within the brainstem nucleus tractus solitarii (nTS), a critical contributor to cardiorespiratory function and site of neuroplasticity. We have shown that decreasing input to the nTS via unilateral vagus nerve transection (vagotomy) induces morphological changes in nTS glia and reduces sighs during hypoxia. The mechanisms behind post-vagotomy changes are not well understood. We hypothesized that chronic vagotomy alters cardiorespiratory responses to vagal afferent stimulation via blunted nTS neuronal activity. Male Sprague-Dawley rats (6 weeks old) underwent right cervical vagotomy caudal to the nodose ganglion, or sham surgery. After 1 week, rats were anaesthetized, ventilated and instrumented to measure mean arterial pressure (MAP), heart rate (HR), and splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA, respectively). Vagal afferent stimulation (2-50 Hz) decreased cardiorespiratory parameters and increased neuronal Ca2+ measured by in vivo photometry and in vitro slice imaging of nTS GCaMP8m. Vagotomy attenuated both these reflex and neuronal Ca2+ responses compared to shams. Vagotomy also reduced presynaptic Ca2+ responses to stimulation (Cal-520 imaging) in the nTS slice. The decrease in HR, SSNA and PhrNA due to nTS nanoinjection of exogenous glutamate also was tempered following vagotomy. This effect was not restored by blocking excitatory amino acid transporters. However, the blunted responses were mimicked by NMDA, not AMPA, nanoinjection and were associated with reduced NR1 subunits in the nTS. Altogether, these results demonstrate that vagotomy induces multiple changes within the nTS tripartite synapse that influence cardiorespiratory reflex responses to afferent stimulation. KEY POINTS: Multiple mechanisms within the nucleus tractus solitarii (nTS) contribute to functional changes following vagal nerve transection. Vagotomy results in reduced cardiorespiratory reflex responses to vagal afferent stimulation and nTS glutamate nanoinjection. Blunted responses occur via reduced presynaptic Ca2+ activation and attenuated NMDA receptor expression and function, leading to a reduction in nTS neuronal activation. These results provide insight into the control of autonomic and respiratory function, as well as the plasticity that can occur in response to nerve damage and cardiorespiratory disease.
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Neuronas , Núcleo Solitario , Ratas , Masculino , Animales , Núcleo Solitario/fisiología , Ratas Sprague-Dawley , Neuronas/fisiología , Vagotomía , Nervio Vago/fisiología , Ácido Glutámico/farmacología , Ácido Glutámico/metabolismoRESUMEN
To investigate noxious stimulation-responsive neural circuits that could influence the gut, we recorded from intestinally directed (efferent) nerve filaments dissected from mesenteric nerves close to the small intestine in anesthetized rats. These exhibited baseline multiunit activity that was almost unaffected by vagotomy (VagX) and reduced only slightly by cutting the splanchnic nerves. The activity was halved by hexamethonium (Hex) treatment. When an adjacent gut segment received an intraluminal stimulus 2,4,6-trinitrobenzenesulfonate (TNBS) in 30% ethanol, mesenteric efferent nerve activity increased for more than 1 h. The increased activity was almost unaffected by bilateral vagotomy or splanchnic nerve section, indicating a lack of central nervous involvement, but it was 60% reduced by hexamethonium. Spike sorting discriminated efferent single and predominantly single-unit spike trains that responded to TNBS, were unaffected by splachnectomy but were silenced by hexamethonium. After noxious stimulation of one segment, the adjacent segment showed no evidence of suppression of gut motility or vasoconstriction. We conclude that luminal application of a noxious stimulus to the small intestine activates an entirely peripheral, intestinointestinal reflex pathway. This pathway involves enteric intestinofugal neurons that excite postganglionic sympathetic neurons via a nicotinic synapse. We suggest that the final sympathetic efferent neurons that respond to a tissue damaging stimulus are distinct from vasoconstrictor, secretomotor, and motility inhibiting neurons.NEW & NOTEWORTHY An intraluminal noxious chemical stimulus applied to one segment of small intestine increased mesenteric efferent nerve activity to an adjacent segment. This was identified as a peripheral ganglionic reflex that did not require vagal or spinal connections. Hexamethonium blocked most, but not all, ongoing and reflex mesenteric efferent activity. The prevertebral sympathetic efferent neurons that are activated likely affect inflammatory and immune functions of other gut segments.
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Reflejo , Nervios Esplácnicos , Ratas , Animales , Hexametonio/farmacología , Reflejo/fisiología , Vagotomía , Nervio Vago/fisiología , Sistema Nervioso Simpático/fisiologíaRESUMEN
INTRODUCTION/PURPOSE: The obesity epidemic is rapidly growing, and visceral adiposity is associated with metabolic consequences secondary to peroxisome proliferator-activated receptor (PPAR)-induced inter-organ signaling pathways. PPARs are ligand-activated transcription factors that modulate vagal pathways which can improve blood pressure, arterial remodeling, cholesterol levels, and insulin sensitivity. However, an obesity-induced inflammatory milieu can interfere with the beneficial effects of PPAR activity, suggesting that a dysregulated PPAR-vagus pathway may play a role in the pathogenesis of obesity-related hypertension. Therefore, we hypothesized that hepatic vagotomy (HV) in patients with obesity would result in a significant reduction in blood pressure and/or the number of hypertension medications compared to control. METHODS: We conducted a retrospective chart review of 160 patients undergoing laparoscopic sleeve gastrectomy. Patients were divided into HV and control groups, and information was collected at each clinic visit. RESULTS: At six-months post-operation, the HV group was found to have significantly lower total cholesterol (TC)/high-density lipoprotein (HDL) ratios than the control group. The HV group also had a numerically better blood profile for TC, HDL, low-density lipoprotein (LDL), triglycerides, C-reactive protein, and LDL/HDL ratio. Hypertensive patients in the HV group showed numerically lower hypertension medication counts after six weeks when compared to control. CONCLUSION: We present the first study to report clinically significant changes related to HV in human subjects. Our results did not support our initial hypothesis but did demonstrate an improvement of the TC/HDL ratio with HV in patients with obesity. Future studies should confirm these findings in a randomized control trial.
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Hipertensión , Obesidad Mórbida , Humanos , Lipoproteínas HDL , Receptores Activados del Proliferador del Peroxisoma , Estudios Retrospectivos , HDL-Colesterol , LDL-Colesterol , Obesidad Mórbida/cirugía , Colesterol , Obesidad/complicaciones , Obesidad/cirugía , Triglicéridos , Hipertensión/cirugía , VagotomíaRESUMEN
INTRODUCTION: Benign gastric outlet obstruction (BGOO) severely impacts the quality of life of patients. The main treatment methods for BGOO include surgery and endoscopy, but both have significant drawbacks. Therefore, this study aims to explore the safety and efficacy of a new technique, to develop a new option for treating BGOO. METHODS AND ANALYSIS: This is an ongoing prospective, single-centre, single-blind randomised controlled trial. The study will be conducted from January 2022 to December 2025, and 50 patients will be enrolled. The participants will be randomly assigned in a 1:1 ratio to either the experimental (stomach-partitioning gastrojejunostomy with distal selective vagotomy) or control groups (conventional gastrojejunostomy with highly selective vagotomy). We will collect baseline characteristics, laboratory tests, auxiliary examinations, operation, postoperative conditions and follow-up data. Follow-up will last for 3 years. The main outcome is the incidence of delayed gastric emptying within 30 days after surgery. Secondary outcomes include the efficacy indicator (consisting of serum gastrin level, pepsinogen level, 13C breath test, gastrointestinal quality of life index, operation time, blood loss and postoperative recovery), a safety evaluation index (consisting of complications and mortality within 30 days after surgery) and follow-up data (consisting of the incidence of primary ulcer progression in 3 years after surgery, and the gastroscopy results in 1 and 3 years after surgery). ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (no. 2021-P2-274-02). The study conformed to the provisions of the Declaration of Helsinki (as revised in 2013). Written informed consent will be obtained prior to study enrolment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100052197.
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Derivación Gástrica , Obstrucción de la Salida Gástrica , Humanos , Vagotomía Gástrica Proximal , Derivación Gástrica/efectos adversos , Derivación Gástrica/métodos , Estudios Prospectivos , Calidad de Vida , Método Simple Ciego , Vagotomía/efectos adversos , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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 avoidance1-3. Here, we show that antigen-specific avoidance behaviour in inbred mice4,5 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.
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Alérgenos , Reacción de Prevención , Hipersensibilidad , Mastocitos , Animales , Ratones , Alérgenos/inmunología , Reacción de Prevención/fisiología , Hipersensibilidad/inmunología , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Estómago/inmunología , Vagotomía , Inmunidad Innata/inmunología , Inmunidad Mucosa/inmunología , Células Th2/inmunología , Citocinas/inmunología , Leucotrienos/biosíntesis , Leucotrienos/inmunología , Intestino Delgado/inmunologíaRESUMEN
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.
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Obstrucción de la Salida Gástrica , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/patología , Estudios de Casos y Controles , Cuidados Paliativos , Estudios Prospectivos , Vagotomía/efectos adversos , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Obstrucción de la Salida Gástrica/patologíaRESUMEN
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 (p > 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an α7nAChR-agonist (p = 0.090). Cervical vagotomy with an α7nAChR-antagonist aggravated lung injury (p = 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 (p = 0.012) and selective vagotomy (p = 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.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Ratas , Animales , Lipopolisacáridos/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Nervio Vago/metabolismo , Vagotomía , Lesión Pulmonar Aguda/metabolismoRESUMEN
In the central nervous system, longterm 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 wellbeing 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 metenkephalin concentrations were evaluated using HPLC and RIA methods. We also defined a concentration of immunederived plasma metenkephalin to establish a longterm 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 inflammationinduced increases of plasma metenkephalin - 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.
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Trastorno del Espectro Autista , Encefalina Metionina , Ratas , Animales , Encefalina Metionina/farmacología , Vagotomía , Nervio Vago/fisiología , Inflamación , AminasRESUMEN
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.
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Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratas , Masculino , Animales , Rotenona/toxicidad , Ácido Gálico/farmacología , Ratas Wistar , Enfermedad de Parkinson/patología , Estrés Oxidativo , Encéfalo , Vagotomía , Electrofisiología , Fármacos Neuroprotectores/farmacología , Modelos Animales de EnfermedadRESUMEN
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 CD11bhigh and CD11blow 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.
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Lesiones Traumáticas del Encéfalo , Vagotomía , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/cirugía , Modelos Animales de Enfermedad , Ratones , Bazo , Nervio Vago/metabolismoRESUMEN
Interactions between the brain and the stomach shape both cognitive and digestive functions. Recent human studies report spontaneous synchronization between brain activity and gastric slow waves in the resting state. However, this finding has not been replicated in any animal models. The neural pathways underlying this apparent stomach-brain synchrony is also unclear. Here, we performed functional magnetic resonance imaging while simultaneously recording body-surface gastric slow waves from anesthetized rats in the fasted vs. postprandial conditions and performed a bilateral cervical vagotomy to assess the role of the vagus nerve. The coherence between brain fMRI signals and gastric slow waves was found in a distributed "gastric network", including subcortical and cortical regions in the sensory, motor, and limbic systems. The stomach-brain coherence was largely reduced by the bilateral vagotomy and was different between the fasted and fed states. These findings suggest that the vagus nerve mediates the spontaneous coherence between brain activity and gastric slow waves, which is likely a signature of real-time stomach-brain interactions. However, its functional significance remains to be established.
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Estómago , Nervio Vago , Humanos , Ratas , Animales , Estómago/fisiología , Nervio Vago/fisiología , Encéfalo/fisiología , Vagotomía , Vías NerviosasRESUMEN
BACKGROUND: The influence of cutting the sub-diaphragmatic branch of the vagus nerve on heart rate variability (HRV) and inflammatory reaction to severe hemorrhagic shock has not been determined prior to this study. METHODS: Male Sprague-Dawley rats were divided into four groups of Sham, sub-diaphragmatic vagotomized (Vag), subacute (135 ± 2 min) hemorrhagic shock (SHS), and sub-diaphragmatic vagotomized with SHS (Vag + SHS). Hemodynamic parameters were recorded and HRV calculated during multiple phases in a conscious model of hemorrhagic shock. The expressions of TNF-α and iNOS were measured in the spleen and lung tissues at the conclusion of the protocol. RESULTS: Decreases in blood pressure during blood withdrawal were identical in the SHS and Vag + SHS groups. However, heart rate only decreased in the Nadir-1 phase of the SHS group. HRV indicated increased power in the very-low, low, and high (VLF, LF, and HF) frequency bands during the Nadir-1 phase of the SHS and Vag + SHS groups, albeit the values were higher in the SHS group. In the recovery phase, the HF bands were only lower in the SHS group. After hemorrhagic shock followed by resuscitation, the expression of TNF-α and iNOS increased in the spleen and lung of the SHS group, and the expression of these genes was significantly lower in the Vag + SHS group than in the SHS group. CONCLUSION: Parasympathetic activity increases during the hypotensive phase of hemorrhagic shock, whereas the cardiac vagal tone decreases in the recovery phase. Sub-diapragmatic vagotomy blunts the cardiac vagal tone during hemorrhagic shock, but its effect is reversed in the recovery phase. The vagus nerve plays a role in proinflammatory responses in the lungs and spleen in subacute hemorrhagic shock followed by resuscitation.
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Neumonía , Choque Hemorrágico , Animales , Modelos Animales de Enfermedad , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Neumonía/etiología , Embarazo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa , VagotomíaRESUMEN
BACKGROUND: Peptic ulcer disease (PUD), once primary a surgical problem, is now medically managed in the majority of patients. The surgical treatment of PUD is now strictly reserved for life-threatening complications. Free perforation, refractory bleeding and gastric outlet obstruction, although rare in the age of medical management of PUD, are several of the indications for surgical intervention. The acute care surgeon caring for patients with PUD should be facile in techniques required for bleeding control, bypass of peptic strictures, and vagotomy with resection and reconstruction. This video procedures and techniques article demonstrates these infrequently encountered, but critical operations. CONTENT VIDEO DESCRIPTION: A combination of anatomic representations and videos of step-by-step instructions on perfused cadavers will demonstrate the key steps in the following critical operations. Graham patch repair of perforated peptic ulcer is demonstrated in both open and laparoscopic fashion. The choice to perform open versus laparoscopic repair is based on individual surgeon comfort. Oversewing of a bleeding duodenal ulcer via duodenotomy and ligation of the gastroduodenal artery is infrequent in the age of advanced endoscopy and interventional radiology techniques, yet this once familiar procedure can be lifesaving. Repair of giant duodenal or gastric ulcers can present a challenging operative dilemma on how to best repair or exclude the defect. Vagotomy and antrectomy, perhaps the least common of all the aforementioned surgical interventions, may require more complex reconstruction than other techniques making it challenging for inexperienced surgeons. A brief demonstration on reconstruction options will be shown, and it includes Roux-en-Y gastrojejunostomy. CONCLUSION: Surgical management of PUD is reserved today for life-threatening complications for which the acute care surgeon must be prepared. This presentation provides demonstration of key surgical principles in management of bleeding and free perforation, as well as gastric resection, vagotomy and reconstruction. LEVEL OF EVIDENCE: Video procedure and technique, not applicable.
Asunto(s)
Úlcera Duodenal , Úlcera Péptica Perforada , Úlcera Péptica , Úlcera Duodenal/complicaciones , Gastrectomía , Humanos , Úlcera Péptica/complicaciones , Úlcera Péptica/cirugía , Úlcera Péptica Perforada/cirugía , Vagotomía/métodosRESUMEN
Obesity may be treated by bariatric procedures and is related to enterohormone release modulation. Nevertheless, a majority of commonly used surgical procedures have a significant impact on vagus nerve function by breaking the connections with its gastric branches. In the case of an intragastric balloon (BAL), this interaction is unclear. However, BAL-induced weight reduction is not long-lasting. Interestingly, this method has not been used in combination with vagotomy (VAG). Thus, we evaluated, for the first time, the short- and long-term effects of combined BAL and VAG using the animal-based translational model and compared these effects with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Wistar rats were fed a high-calorie diet for 8 weeks to induce obesity before SG, RYGB, BAL + / - VAG. Animals' weight and eating behaviors were monitored weekly. After 90 days, serum samples were collected to evaluate postprandial and fasting GLP-1, GIP, PYY, ghrelin, glucagon, insulin, leptin, and pancreatic polypeptide concentrations by fluorescent assay. VAG, SG, RYGB, and BAL + VAG significantly reduced body weight 30 and 90 days after surgery. BAL alone induced temporal weight reduction observed after 30 days, reversed after 90 days. Calories intake was reduced at the first half of the observation period in all groups. Fluid intake was reduced in all groups except SG and BAL. Enterohormone profile for BAL + VAG was comparable to SG and RYGB but not BAL. VAG and BAL + VAG but not BAL alone maintain weight reduction, alimentary intake changes, and enterohormone release after long-term observation. VAG may improve the effectiveness of bariatric procedures for obesity treatment in clinical practice.
Asunto(s)
Cirugía Bariátrica , Balón Gástrico , Derivación Gástrica , Obesidad Mórbida , Animales , Cirugía Bariátrica/métodos , Gastrectomía/métodos , Derivación Gástrica/métodos , Obesidad/cirugía , Obesidad Mórbida/cirugía , Ratas , Ratas Wistar , Vagotomía , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: Postoperative ileus (POI) involves an intestinal inflammatory response that is modulated by afferent and efferent vagal activation. We aimed to identify the potential influence of the vagus nerve on POI by tracking central vagal activation and its role for peripheral inflammatory changes during the early hours after surgery. METHODS: C57BL6 mice were vagotomized (V) 3-4 days prior to experiments, while control animals received sham vagotomy (SV). Subgroups underwent either laparotomy (sham operation; S-POI) or laparotomy followed by standardized small bowel manipulation to induce postoperative ileus (POI). Three hours and 9 h later, respectively, a jejunal segment was harvested and infiltration of inflammatory cells in intestinal muscularis was evaluated by fluorescein isothiocyanate (FITC) avidin and myeloperoxidase (MPO) staining. Moreover, the brain stem was harvested, and central nervous activation was investigated by Fos immunochemistry in both the nucleus of the solitary tract (NTS) and the area postrema (AP). Data are presented as mean ± SEM, and a p < 0.05 was considered statistically significant. KEY RESULTS: Three hour experiments revealed no significant differences between all experimental groups, except MPO staining: 3 h after abdominal surgery, there were significantly more MPO-positive cells in vagotomized S-POI animals compared to sham-vagotomized S-POI animals (26.7 ± 7.1 vs. 5.1 ± 2.4, p < 0.01). Nine hour postoperatively intramuscular mast cells (IMMC) were significantly decreased in the intestinal muscularis of V/POI animals compared to SV/POI animals (1.5 ± 0.3 vs. 5.9 ± 0.2, p < 0.05), while MPO-positive cells were increased in V/POI animals compared to SV/POI animals (713.2 ± 99.4 vs. 46.9 ± 5.8, p < 0.05). There were less Fos-positive cells in the NTS of V/POI animals compared to SV/POI animals (64.7 ± 7.8 vs. 132.8 ± 23.9, p < 0.05) and more Fos-positive cells in the AP of V/POI animals compared to SV/POI animals 9 h postoperatively (38.0 ± 2.0 vs. 13.7 ± 0.9, p < 0.001). CONCLUSIONS AND INTERFERENCES: Afferent nerve signaling to the central nervous system during the development of early POI seems to be mediated mainly via the vagus nerve and to a lesser degree via systemic circulation. During the early hours of POI, the intestinal immune response may be attenuated by vagal modulation, suggesting interactions between the central nervous system and the intestine.
Asunto(s)
Motilidad Gastrointestinal , Ileus , Animales , Motilidad Gastrointestinal/fisiología , Ileus/etiología , Ratones , Ratones Endogámicos C57BL , Complicaciones Posoperatorias , Vagotomía , Nervio Vago/fisiologíaRESUMEN
BACKGROUND: Sepsis often results in acute lung injury (ALI). Dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in lipopolysaccharide (LPS)-induced ALI rats. METHODS: The bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed as sham surgery. After LPS administration, Dex antagonist yohimbine (YOH) and/or Dex was injected intraperitoneally to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores. The plasma concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), catecholamine and acetylcholine were measured with enzyme-linked immunosorbent assay. RESULTS: The median survival time of LPS-induced ALI rats was prolonged by Dex (22 h, 95% CI, [24.46, 92.20]) vs. 14 h, 95% CI, [14.60, 89.57] of the LPS control group, P < 0.05), and the ALI score was reduced by Dex (6.5, 95% CI, [5.23, 8.10] vs. 11.5, 95% CI, [10.23, 13.10] in the LPS group, P < 0.01). However, these protective effects were significantly decreased by either YOH administration or vagotomy. Dex decreased LPS-induced IL-1ß, TNF-α, and catecholamine but increased acetylcholine in blood serum; these effects of Dex was partially abolished by vagotomy. CONCLUSIONS: Our data suggested that Dex increased vagal nerve tone that partially contributed to its anti-inflammatory and lung-protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α2-adrenoceptor activation, respectively.