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Sample records for hepatic vagus nerve

  1. Neurofibrosarcoma of the vagus nerve

    PubMed Central

    Corris, P. A.

    1983-01-01

    A patient whose symptoms of cough and intermittent hoarseness were due to a neurofibrosarcoma of the vagus nerve is described. Attention is drawn to the rarity of the tumour and a short review of the pathology and treatment of neurofibrosarcoma is discussed. ImagesFig. 1 PMID:6844194

  2. [Paraganglioma of the vagus nerve].

    PubMed

    Torres-Carranza, E; Infante-Cossío, P; García-Perla, A; Belmonte, R; Menéndez, J; Gutiérrez-Pérez, J L

    2006-06-01

    Paragangliomas of the vagus nerve are uncommon vascular benign neoplasms of neuroectodermic origin. Initial clinical manifestation is usually as an asymptomatic cervical mass, although sometimes may cause lower cranial nerve palsies. These paragangliomas seldom associate to high levels of circulating catecholamines. Diagnosis is based on the clinics aided by imaging, where CT and MRI play an important role. Angiography is not only diagnostic, but it also allows preoperative embolization of the mass. Most accepted treatment is surgical removal, even though some paragangliomas are suitable for radiation therapy in very specific patients. In this paper we describe a new case of paraganglioma of the vagus nerve in a cervical location, with hypertensive episodes and high catecholamine-levels. The authors review the literature describing the clinical presentation, the diagnosis and the treatment of this rare lesion. PMID:16855784

  3. Hepatic Branch Vagus Nerve Plays a Critical Role in the Recovery of Post-Ischemic Glucose Intolerance and Mediates a Neuroprotective Effect by Hypothalamic Orexin-A

    PubMed Central

    Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo

    2014-01-01

    Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A. PMID:24759941

  4. Central activating transcription factor 4 (ATF4) regulates hepatic insulin resistance in mice via S6K1 signaling and the vagus nerve.

    PubMed

    Zhang, Qian; Yu, Junjie; Liu, Bin; Lv, Ziquan; Xia, Tingting; Xiao, Fei; Chen, Shanghai; Guo, Feifan

    2013-07-01

    Recent studies have revealed that the central nervous system, particularly the hypothalamus, is critical for regulating insulin sensitivity in peripheral tissues. The aim of our current study is to investigate the possible involvement of hypothalamic activating transcription factor 4 (ATF4) in the regulation of insulin sensitivity in the liver. Here, we show that overexpression of ATF4 in the hypothalamus resulting from intracerebroventricular injection of adenovirus expressing ATF4 induces hepatic insulin resistance in mice and that inhibition of hypothalamic ATF4 by intracerebroventricular adenovirus expressing a dominant-negative ATF4 variant has the opposite effect. We also show that hypothalamic ATF4-induced insulin resistance is significantly blocked by selective hepatic vagotomy or by inhibiting activity of the mammalian target of rapamycin (mTOR) downstream target S6K1. Finally, we show that inhibition of hypothalamic ATF4 reverses hepatic insulin resistance induced by acute brain endoplasmic reticulum (ER) stress. Taken together, our study describes a novel central pathway regulating hepatic insulin sensitivity that is mediated by hypothalamic ATF4/mTOR/S6K1 signaling and the vagus nerve and demonstrates an important role for hypothalamic ATF4 in brain ER stress-induced hepatic insulin resistance. These results may lead to the identification of novel therapeutic targets for treating insulin resistance and associated metabolic diseases. PMID:23454693

  5. Central Activating Transcription Factor 4 (ATF4) Regulates Hepatic Insulin Resistance in Mice via S6K1 Signaling and the Vagus Nerve

    PubMed Central

    Zhang, Qian; Yu, Junjie; Liu, Bin; Lv, Ziquan; Xia, Tingting; Xiao, Fei; Chen, Shanghai; Guo, Feifan

    2013-01-01

    Recent studies have revealed that the central nervous system, particularly the hypothalamus, is critical for regulating insulin sensitivity in peripheral tissues. The aim of our current study is to investigate the possible involvement of hypothalamic activating transcription factor 4 (ATF4) in the regulation of insulin sensitivity in the liver. Here, we show that overexpression of ATF4 in the hypothalamus resulting from intracerebroventricular injection of adenovirus expressing ATF4 induces hepatic insulin resistance in mice and that inhibition of hypothalamic ATF4 by intracerebroventricular adenovirus expressing a dominant-negative ATF4 variant has the opposite effect. We also show that hypothalamic ATF4-induced insulin resistance is significantly blocked by selective hepatic vagotomy or by inhibiting activity of the mammalian target of rapamycin (mTOR) downstream target S6K1. Finally, we show that inhibition of hypothalamic ATF4 reverses hepatic insulin resistance induced by acute brain endoplasmic reticulum (ER) stress. Taken together, our study describes a novel central pathway regulating hepatic insulin sensitivity that is mediated by hypothalamic ATF4/mTOR/S6K1 signaling and the vagus nerve and demonstrates an important role for hypothalamic ATF4 in brain ER stress–induced hepatic insulin resistance. These results may lead to the identification of novel therapeutic targets for treating insulin resistance and associated metabolic diseases. PMID:23454693

  6. Endocrine tumors associated with the vagus nerve.

    PubMed

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-09-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID:27406876

  7. Subdiaphragmatic vagus nerve activity and hepatic venous glucose are differentially regulated by the central actions of insulin in Wistar and SHR

    PubMed Central

    Ribeiro, Izabela Martina R; Ferreira-Neto, Hildebrando C; Antunes, Vagner R

    2015-01-01

    Glucose is the most important energy substrate for the maintenance of tissues function. The liver plays an essential role in the control of glucose production, since it is able to synthesize, store, and release glucose into the circulation under different situations. Hormones like insulin and catecholamines influence hepatic glucose production (HGP), but little is known about the role of the central actions of physiological doses of insulin in modulating HGP via the autonomic nervous system in nonanesthetized rats especially in SHR where we see a high degree of insulin resistance and metabolic dysfunction. Wistar and SHR received ICV injection of insulin (100 nU/μL) and hepatic venous glucose concentration (HVGC) was monitored for 30 min, as an indirect measure of HGP. At 10 min after insulin injection, HVGC decreased by 27% in Wistar rats, with a negligible change (3%) in SHR. Pretreatment with atropine totally blocked the reduction in HVGC, while pretreatment with propranolol and phentolamine induced a decrease of 8% in HVGC after ICV insulin injection in Wistar. Intracarotid infusion of insulin caused a significant increase in subdiaphragmatic vagus nerve (SVN) activity in Wistar (12 ± 2%), with negligible effects on the lumbar splanchnic sympathetic nerve (LSSN) activity (−6 ± 3%). No change was observed in SVN (−2 ± 2%) and LSSN activities (2 ± 3%) in SHR after ICA insulin infusion. Taken together, these results show, in nonanesthetized animals, the importance of the parasympathetic nervous system in controlling HVGC, and subdiaphragmatic nerve activity following central administration of insulin; a mechanism that is impaired in the SHR. PMID:25948821

  8. Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation.

    PubMed

    Hays, Seth A

    2016-04-01

    Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation. PMID:26671658

  9. Vagus Nerve Stimulation and Food Intake

    PubMed Central

    Schneider, Kristin L.; Oleski, Jessica; Gordon, Katherine; Rothschild, Anthony J.; Pagoto, Sherry L.

    2014-01-01

    Animal research suggests that vagus nerve stimulation (VNS) is associated with weight loss and decreased appetite. Results from human studies are mixed; some suggest that VNS affects weight whereas others do not, and it is unclear how VNS affects eating behaviors. Baseline body mass index (BMI) and VNS device settings may moderate the effects of VNS on caloric intake. This study investigates the association among BMI, VNS device settings, and caloric intake of highly palatable foods during VNS on versus VNS off sessions in 16 adult patients (62.5% female; BMI mean = 29.11 ± 6.65) using VNS therapy for either epilepsy or depression. Participants attended 2 experimental sessions (VNS on versus off) where they were presented with 4 preferred snack foods totaling 1600 calories. At the start of the session, they either had their VNS devices turned off or left on. Caloric intake was calculated by weighing foods before and after each session. BMI category (overweight/obese and lean) was the between group factor in the analysis. After controlling for covariates, an interaction of condition and BMI category (P = .03) was found. There was an interaction of condition and device output current (P = .05) and a trend toward an interaction of condition and device on time (P = .07). Excess weight may impact how neurobiological signals from the vagus nerve affect appetite and eating. Future research is needed to further elucidate this relationship. PMID:24876624

  10. Vagus Nerve Stimulation for Major Depressive Episodes.

    PubMed

    Eljamel, Sam

    2015-01-01

    Stimulation of the left vagus nerve is a novel antidepressive therapy that relies upon the vagal projections to the brain stem to modulate brain circuits involved in mood regulation. There is cumulative evidence from prospective and long-term studies that has demonstrated tolerability and effectiveness of vagus nerve stimulation (VNS) in major depressive episodes (MDE). VNS in MDE has the following advantages: symptomatic response (defined as at least a 50% improvement in MDE severity) occurs in at least 15-17% of patients after 10 weeks of VNS treatment and in at least 22-37% of patients after 12 months of VNS treatment, remissions are observed in at least 15-17% of patients after 12 months of treatment, there is a sustained response in 13-27% of patients during 12 months of VNS, and successful maintenance of the initial improvement is observed in a high percentage of patients (73-77% of patients who had meaningful or greater benefit after 3 months of treatment maintained at least meaningful benefit after 12 months of treatment). VNS is a well-tolerated treatment as indicated by the high continuation rates of VNS therapy in the D01 and D02 studies after 12 months of therapy (90-98%) and the low rate of adverse event-related study discontinuations through 12 months or more in these studies (3%). Adverse effects are characterized by the absence of systemic effects associated with drug therapy and are primarily limited to those related to stimulation of the vagus nerve; many of the common adverse effects only occurred when VNS was on with the ability to stop acute stimulation-related adverse effects immediately through the use of magnet deactivation of the VNS device. More importantly, there were no adverse cognitive and psychomotor effects observed with antidepressant drugs and electroconvulsive therapy, no overdose toxicity observed with antidepressant drugs, favorable findings in animal reproductive studies, and an ability to add VNS therapy to antidepressant drug

  11. Revision surgeries following vagus nerve stimulator implantation.

    PubMed

    Lam, Sandi; Lin, Yimo; Curry, Daniel J; Reddy, Gaddum D; Warnke, Peter C

    2016-08-01

    The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were <1%, <3%, 4-10%, and <1% for VNS electrode revision, battery revision/removal, battery replacement/implantation, and infection washout, respectively. For electrode revision and battery revision/replacement, the incidence was higher in the first year and for battery replacement in later years. Age, sex, insurance type, or geographic region did not significantly impact event occurrence. Implant-related revision surgeries are rare. Some events occur more often in certain follow-up years than others; none are significantly impacted by age, sex, insurance type, or geographic region. The most common reason for revision was battery replacement several years after VNS placement. PMID:27050913

  12. Cerebral blood flow changes during vagus nerve stimulation for depression.

    PubMed

    Conway, Charles R; Sheline, Yvette I; Chibnall, John T; George, Mark S; Fletcher, James W; Mintun, Mark A

    2006-03-31

    Positron emission tomography (PET oxygen-15 labeled water or PET [15O]H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to acute vagus nerve stimulation (VNS) in four subjects with treatment-resistant major depression (TRMD). Four 90-s PET [15O]H2O scans were performed on each subject in an off-on sequence (2 VNS de-activated; 2 VNS activated). PET images were aligned, normalized for global uptake, and resampled to standard atlas space. Statistical t-images were used to evaluate change. VNS-induced increases in rCBF were found in the bilateral orbitofrontal cortex, bilateral anterior cingulate cortex, and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with depression and the afferent pathways of the vagus nerve. PMID:16510266

  13. Vagus nerve stimulation therapy in partial epilepsy: a review.

    PubMed

    Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

    2016-09-01

    Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions. PMID:26908034

  14. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

    NASA Astrophysics Data System (ADS)

    Borovikova, Lyudmila V.; Ivanova, Svetlana; Zhang, Minghuang; Yang, Huan; Botchkina, Galina I.; Watkins, Linda R.; Wang, Haichao; Abumrad, Naji; Eaton, John W.; Tracey, Kevin J.

    2000-05-01

    Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

  15. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    PubMed

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. PMID:24553102

  16. High-resolution measurement of electrically-evoked vagus nerve activity in the anesthetized dog

    NASA Astrophysics Data System (ADS)

    Yoo, Paul B.; Lubock, Nathan B.; Hincapie, Juan G.; Ruble, Stephen B.; Hamann, Jason J.; Grill, Warren M.

    2013-04-01

    Objective. Not fully understanding the type of axons activated during vagus nerve stimulation (VNS) is one of several factors that limit the clinical efficacy of VNS therapies. The main goal of this study was to characterize the electrical recruitment of both myelinated and unmyelinated fibers within the cervical vagus nerve. Approach. In anesthetized dogs, recording nerve cuff electrodes were implanted on the vagus nerve following surgical excision of the epineurium. Both the vagal electroneurogram (ENG) and laryngeal muscle activity were recorded in response to stimulation of the right vagus nerve. Main results. Desheathing the nerve significantly increased the signal-to-noise ratio of the ENG by 1.2 to 9.9 dB, depending on the nerve fiber type. Repeated VNS following nerve transection or neuromuscular block (1) enabled the characterization of A-fibers, two sub-types of B-fibers, and unmyelinated C-fibers, (2) confirmed the absence of stimulation-evoked reflex compound nerve action potentials in both the ipsilateral and contralateral vagus nerves, and (3) provided evidence of stimulus spillover into muscle tissue surrounding the stimulating electrode. Significance. Given the anatomical similarities between the canine and human vagus nerves, the results of this study provide a template for better understanding the nerve fiber recruitment patterns associated with VNS therapies.

  17. Vagus nerve electrical stimulation inhibits serum levels of S100A8 protein in septic shock rats.

    PubMed

    Lei, Ming; Liu, Xin-Xin

    2016-05-01

    The vagus nerve and the released acetylcholine exert anti-inflammatory effects and inhibit septic shock. However, their detailed mechanisms remain to be elucidated. The present study aimed to investigate the effects of vagus nerve electrical stimulation on serum S100A8 levels in septic shock rats. A total of 36 male Sprague-Dawley rats were randomly divided into six equal groups: i) Sham group, receiving sham operation; ii) CLP group, subjected to cecal ligation and puncture (CLP) to establish a model of polymicrobial sepsis; iii) VGX group, subjected to CLP and bilateral cervical vagotomy; iv) STM group, subjected to CLP, bilateral cervical vagotomy and electrical stimulation on the left vagus nerve trunk; v) α‑bungarotoxin (BGT) group was administered α‑BGT prior to electrical stimulation; vi) Anti‑receptor for advanced glycation end products (RAGE) group, administered intraperitoneal injection of anti‑RAGE antibody prior to electrical stimulation. The right carotid artery was cannulated to monitor mean artery pressure (MAP). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess the liver function. Serum S100A8 and advanced glycation end product (AGE) levels were measured using enzyme‑linked immunosorbent assays. The expression of hepatic RAGE was determined by western blotting. The present study revealed that Sprague‑Dawley rats exhibited progressive hypotension and significantly increased serum AST and ALT levels following CLP challenge compared with the sham group. The levels of S100A8 and AGEs, and the protein expression of hepatic RAGE were significantly increased following CLP compared with the sham group. Vagus nerve electrical stimulation significantly prevented the development of CLP‑induced hypotension, alleviated the hepatic damage, reduced serum S100A8 and AGEs production, and reduced the expression of hepatic RAGE. The inhibitory effect of vagus nerve electrical

  18. The effect of transcutaneous vagus nerve stimulation on cortical excitability.

    PubMed

    Capone, Fioravante; Assenza, Giovanni; Di Pino, Giovanni; Musumeci, Gabriella; Ranieri, Federico; Florio, Lucia; Barbato, Carmen; Di Lazzaro, Vincenzo

    2015-05-01

    There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60 min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60 min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique. PMID:25182412

  19. Intraoperative Vagus Nerve Monitoring: A Transnasal Technique during Skull Base Surgery

    PubMed Central

    Schutt, Christopher A.; Paskhover, Boris; Judson, Benjamin L.

    2014-01-01

    Objectives Intraoperative vagus nerve monitoring during skull base surgery has been reported with the use of an oral nerve monitoring endotracheal tube. However, the intraoral presence of an endotracheal tube can limit exposure by its location in the operative field during transfacial approaches and by limiting superior mobilization of the mandible during transcervical approaches. We describe a transnasal vagus nerve monitoring technique. Design and Participants Ten patients underwent open skull base surgery. Surgical approaches included transcervical (five), transfacial/maxillary swing (three), and double mandibular osteotomy (two). The vagus nerve was identified, stimulated, and monitored in all cases. Main Outcome Measures Intraoperative nerve stimulation, pre- and postoperative vagus nerve function through the use of flexible laryngoscopy in conjunction with assessment of subjective symptoms of hoarseness, voice change, and swallowing difficulty. Results Three patients had extensive involvement of the nerve by tumor with complete postoperative nerve deficit, one patient had a transient deficit following dissection of tumor off of nerve with resolution, and the remaining patients had nerve preservation. One patient experienced minor epistaxis during monitor tube placement that was managed conservatively. Conclusions Transnasal vagal nerve monitoring is a simple method that allows for intraoperative monitoring during nerve preservation surgery without limiting surgical exposure. PMID:25844292

  20. Targeting plasticity with vagus nerve stimulation to treat neurological disease.

    PubMed

    Hays, Seth A; Rennaker, Robert L; Kilgard, Michael P

    2013-01-01

    Pathological neural activity in a variety of neurological disorders could be treated by directing plasticity to specifically renormalize aberrant neural circuits, thereby restoring normal function. Brief bursts of acetylcholine and norepinephrine can enhance the neural plasticity associated with coincident events. Vagus nerve stimulation (VNS) represents a safe and effective means to trigger the release of these neuromodulators with a high degree of temporal control. VNS-event pairing can generate highly specific and long-lasting plasticity in sensory and motor cortex. Based on the capacity to drive specific changes in neural circuitry, VNS paired with experience has been successful in effectively ameliorating animal models of chronic tinnitus, stroke, and posttraumatic stress disorder. Targeted plasticity therapy utilizing VNS is currently being translated to humans to treat chronic tinnitus and improve motor recovery after stroke. This chapter will discuss the current progress of VNS paired with experience to drive specific plasticity to treat these neurological disorders and will evaluate additional future applications of targeted plasticity therapy. PMID:24309259

  1. Photostimulation of sensory neurons of the rat vagus nerve

    NASA Astrophysics Data System (ADS)

    Rhee, Albert Y.; Li, Gong; Wells, Jonathon; Kao, Joseph P. Y.

    2008-02-01

    We studied the effect of infrared (IR) stimulation on rat sensory neurons. Primary sensory neurons were prepared by enzymatic dissociation of the inferior (or "nodose") ganglia from the vagus nerves of rats. The 1.85-μm output of a diode laser, delivered through a 200-μm silica fiber, was used for photostimulation. Nodose neurons express the vanilloid receptor, TRPV1, which is a non-selective cation channel that opens in response to significant temperature jumps above 37 C. Opening TRPV1 channels allows entry of cations, including calcium (Ca 2+), into the cell to cause membrane depolarization. Therefore, to monitor TRPV1 activation consequent to photostimulation, we used fura-2, a fluorescent Ca 2+ indicator, to monitor the rise in intracellular Ca 2+ concentration ([Ca 2+]i). Brief trains of 2-msec IR pulses activated TRPV1 rapidly and reversibly, as evidenced by transient rises in [Ca 2+]i (referred to as Ca 2+ transients). Consistent with the Ca 2+ transients arising from influx of Ca 2+, identical photostimulation failed to evoke Ca 2+ responses in the absence of extracellular Ca 2+. Furthermore, the photo-induced Ca 2+ signals were abolished by capsazepine, a specific blocker of TRPV1, indicating that the responses were indeed mediated by TRPV1. We discuss the feasibility of using focal IR stimulation to probe neuronal circuit properties in intact neural tissue, and compare IR stimulation with another photostimulation technique-focal photolytic release of "caged" molecules.

  2. Mechanical Ptosis in Neurofibromatosis Type 1 Heralding the Diagnosis of Right Sided Cervical Vagus Nerve Neurofibroma: A Rare Case Report

    PubMed Central

    Parija, Sucheta; Panda, Bijnya; Pujahari, Susanta; Jena, Satyaswarup

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder. In NF1, involvement of vagus nerve can occur in the form of neurofibroma. A few cases of neurofibroma of thoracic vagus nerve have been reported while neurofibroma of cervical vagus nerve with NF1 is quite rare. A 19-year-old male came with complaints of decreased vision of both eyes and right sided drooping of eyelid since childhood. He was diagnosed as having NF1 with neurofibroma of right cervical vagus nerve. PMID:27504321

  3. Mechanical Ptosis in Neurofibromatosis Type 1 Heralding the Diagnosis of Right Sided Cervical Vagus Nerve Neurofibroma: A Rare Case Report.

    PubMed

    Mallick, Jyotiranjan; Parija, Sucheta; Panda, Bijnya; Pujahari, Susanta; Jena, Satyaswarup

    2016-06-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder. In NF1, involvement of vagus nerve can occur in the form of neurofibroma. A few cases of neurofibroma of thoracic vagus nerve have been reported while neurofibroma of cervical vagus nerve with NF1 is quite rare. A 19-year-old male came with complaints of decreased vision of both eyes and right sided drooping of eyelid since childhood. He was diagnosed as having NF1 with neurofibroma of right cervical vagus nerve. PMID:27504321

  4. Vagus nerve stimulation in neuropsychiatry: Targeting anatomy-based stimulation sites.

    PubMed

    Trevizol, Alisson; Barros, Mirna Duarte; Liquidato, Bianca; Cordeiro, Quirino; Shiozawa, Pedro

    2015-10-01

    The vagus nerve (VN) is the longest cranial nerve, extending from the brain to the abdominal cavity. The VN consists of both afferent and efferent fibers (respectively 80% and 20%). Vagus nerve stimulation (VNS) is a neuromodulation strategy first developed in the 1980s for epilepsy. More recently, growing efforts in clinical research have been underscoring possible clinical benefits of VNS for different medical conditions such as epilepsy, major depression, anxiety disorders, and Tourette syndrome. Following the rational of VN anatomy and cranial innervation presented above, we hereby hypothesize that transcutaneously placing electrodes over the mastoid process could be a useful study protocol for future tVNS trials. PMID:26262931

  5. Vagus Nerve Stimulation Therapy: Indications, Programing, and Outcomes

    PubMed Central

    YAMAMOTO, Takamichi

    2015-01-01

    Vagus nerve stimulation (VNS) provides palliation of seizure reduction for patients with medically refractory epilepsy. VNS is indicated for symptomatic localization-related epilepsy with multiple and bilateral independent foci, symptomatic generalized epilepsy with diffuse epileptogenic abnormalities, refractory idiopathic generalized epilepsy, failed intracranial epilepsy surgery, and other several reasons of contraindications to epilepsy surgery. Programing of the parameters is a principal part in VNS. Output current and duty cycle should be adjusted to higher settings particularly when a patient does not respond to the initial setting, since the pivotal randomized trials performed in the United States demonstrated high stimulation made better responses in seizure frequency. These trials revealed that a ≥ 50% seizure reduction occurred in 36.8% of patients at 1 year, in 43.2% at 2 years, and in 42.7% at 3 years in 440 patients. Safety of VNS was also confirmed because side effects including hoarseness, throat discomfort, cough, paresthesia, and headache improved progressively during the period of 3 years. The largest retrospective study with 436 patients demonstrated the mean seizure reduction of 55.8% in nearly 5 years, and also found 75.5% at 10 years in 65 consecutive patients. The intermediate analysis report of the Japan VNS Registry showed that 60% of 164 cases got a ≥ 50% seizure reduction in 12 months. In addition to seizure reduction, VNS has positive effects in mood and improves energy level, memory difficulties, social aspects, and fear of seizures. VNS is an effective and safe option for patients who are not suitable candidates for intracranial epilepsy surgery. PMID:25925759

  6. Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity

    PubMed Central

    Pardo, JV; Sheikh, SA; Kuskowski, MA; Surerus-Johnson, C; Hagen, MC; Lee, JT; Rittberg, BR; Adson, DE

    2008-01-01

    Fourteen patients were treated over 2 years with cervical vagus nerve stimulation (VNS) for adjunctive therapy of severe, treatment-resistant depression. Here, we report the serendipitous observation that this treatment was associated with highly significant, gradual weight loss despite the patients’ report of not dieting or exercising. The weight loss was proportional to the initial BMI, that is, the more severe the obesity, the greater the weight loss. Weight loss did not correlate with changes in mood symptoms. The vagus nerve carries visceral information to and from the brain; modulation of its activity may alter eating behavior. Chronic cervical VNS may merit controlled study for the treatment of severe obesity. PMID:17563762

  7. The vagus nerve and the inflammatory reflex—linking immunity and metabolism

    PubMed Central

    Pavlov, Valentin A.; Tracey, Kevin J.

    2014-01-01

    The vagus nerve has an important role in regulation of metabolic homeostasis, and efferent vagus nerve-mediated cholinergic signalling controls immune function and proinflammatory responses via the inflammatory reflex. Dysregulation of metabolism and immune function in obesity are associated with chronic inflammation, a critical step in the pathogenesis of insulin resistance and type 2 diabetes mellitus. Cholinergic mechanisms within the inflammatory reflex have, in the past 2 years, been implicated in attenuating obesity-related inflammation and metabolic complications. This knowledge has led to the exploration of novel therapeutic approaches in the treatment of obesity-related disorders. PMID:23169440

  8. Optimization of epilepsy treatment with vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

    2007-11-01

    Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the

  9. Chronic migraine headache prevention with noninvasive vagus nerve stimulation

    PubMed Central

    Calhoun, Anne H.; Lipton, Richard B.; Grosberg, Brian M.; Cady, Roger K.; Dorlas, Stefanie; Simmons, Kristy A.; Mullin, Chris; Liebler, Eric J.; Goadsby, Peter J.; Saper, Joel R.

    2016-01-01

    Objective: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks. Methods: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability. Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use. Results: Fifty-nine participants (mean age, 39.2 years; mean headache frequency, 21.5 d/mo) were enrolled. During the randomized phase, tolerability was similar for nVNS (n = 30) and sham treatment (n = 29). Most adverse events were mild/moderate and transient. Mean changes in the number of headache days were −1.4 (nVNS) and −0.2 (sham) (Δ = 1.2; p = 0.56). Twenty-seven participants completed the open-label phase. For the 15 completers initially assigned to nVNS, the mean change from baseline in headache days after 8 months of treatment was −7.9 (95% confidence interval −11.9 to −3.8; p < 0.01). Conclusions: Therapy with nVNS was well-tolerated with no safety issues. Persistent prophylactic use may reduce the number of headache days in CM; larger sham-controlled studies are needed. ClinicalTrials.gov identifier: NCT01667250. Classification of evidence: This study provides Class II evidence that for patients with CM, nVNS is safe, is well-tolerated, and did not significantly change the number of headache days. This pilot study lacked the precision to exclude important safety issues or benefits of nVNS. PMID:27412146

  10. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis.

    PubMed

    Koopman, Frieda A; Chavan, Sangeeta S; Miljko, Sanda; Grazio, Simeon; Sokolovic, Sekib; Schuurman, P Richard; Mehta, Ashesh D; Levine, Yaakov A; Faltys, Michael; Zitnik, Ralph; Tracey, Kevin J; Tak, Paul P

    2016-07-19

    Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the "inflammatory reflex," is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases. PMID:27382171

  11. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis

    PubMed Central

    Koopman, Frieda A.; Chavan, Sangeeta S.; Miljko, Sanda; Grazio, Simeon; Sokolovic, Sekib; Schuurman, P. Richard; Mehta, Ashesh D.; Levine, Yaakov A.; Faltys, Michael; Zitnik, Ralph; Tracey, Kevin J.; Tak, Paul P.

    2016-01-01

    Rheumatoid arthritis (RA) is a heterogeneous, prevalent, chronic autoimmune disease characterized by painful swollen joints and significant disabilities. Symptomatic relief can be achieved in up to 50% of patients using biological agents that inhibit tumor necrosis factor (TNF) or other mechanisms of action, but there are no universally effective therapies. Recent advances in basic and preclinical science reveal that reflex neural circuits inhibit the production of cytokines and inflammation in animal models. One well-characterized cytokine-inhibiting mechanism, termed the “inflammatory reflex,” is dependent upon vagus nerve signals that inhibit cytokine production and attenuate experimental arthritis severity in mice and rats. It previously was unknown whether directly stimulating the inflammatory reflex in humans inhibits TNF production. Here we show that an implantable vagus nerve-stimulating device in epilepsy patients inhibits peripheral blood production of TNF, IL-1β, and IL-6. Vagus nerve stimulation (up to four times daily) in RA patients significantly inhibited TNF production for up to 84 d. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly. Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans. These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases. PMID:27382171

  12. Protective effects of an interaction between vagus nerve and melatonin on gastric ischemia/reperfusion: the role of oxidative stress

    PubMed Central

    Shahrokhi, Nader; Khaksari, Mohammad; Nourizad, Shahla; Shahrokhi, Nava; Soltani, Zahra; Gholamhosseinian, Ahmad

    2016-01-01

    Objectives: Vagal pathways in gastrointestinal tract are the most important pathways that regulate ischemia/reperfusion (I/R). Gastrointestinal tract is one of the important sources of melatonin production. The aim of this study was to investigate probable protective effect of the interaction between vagus nerve and melatonin after I/R. Materials and methods: This study was performed in male rats that were divided into six groups. Cervical vagus nerve was cut bilaterally after induction of I/R and the right one was stimulated by stimulator. Melatonin or vehicle was injected intraperitoneally. The stomach was removed for histopathological and biochemical investigations. Results: A significant decrease in infiltration of gastric neutrophils and malondialdehyde (MDA) level after I/R was induced by melatonin and was disappeared after vagotomy. The stimulation of vagus nerve significantly enhanced these effects of melatonin. However, a stimulation of vagus nerve alone increased neutrophils infiltration and MDA level. Melatonin significantly increased the activities of catalase, glutathione peroxidase (GPx), superoxide dismutases (SOD). Unlike stimulation of vagus nerve, vagotomy decreased these effects of melatonin. Conclusion: According to these results, it is probable that protective effects of melatonin after I/R may be mediated by vagus nerve. Therefore, there is an interaction between melatonin and vagus nerve in their protective effects. PMID:27096067

  13. The feeding responses evoked by cholecystokinin are mediated by vagus and splanchnic nerves.

    PubMed

    Brown, Thelma A L; Washington, Martha C; Metcalf, Shannon A; Sayegh, Ayman I

    2011-08-01

    Total or selective branch vagotomy attenuates the reduction of cumulative food intake by cholecystokinin (CCK)-8 and CCK-33 respectively. However, the role of the sympathetic innervation of the gut and the role of the vagus nerve in feeding responses, which include meal size (MS) and intermeal interval (IMI), evoked by CCK-8 and CCK-33 have not been evaluated. Here, we tested the effects of total subdiaphragmatic vagotomy (VGX) and celiaco-mesenteric ganglionectomy (CMGX) on the previous feeding responses by CCK-8 and CCK-33 (0, 1, 3, and 5 nmol/kg given intraperitoneally). We found (1) that both peptides reduced meal size and CCK-8 (5 nmol) and CCK-33 (1 and 3 nmol) prolonged IMI, (2) that VGX attenuated the reduction of MS but failed to attenuate the prolongation of IMI by both peptides and (3) that CMGX attenuated the reduction of meal size by CCK-8 and the prolongation of IMI by both peptides. Therefore, the feeding responses evoked by CCK-8 require intact vagus and splanchnic nerves: the reduction of MS by CCK-33 requires an intact vagus nerve, and the prolongation of IMI requires the splanchnic nerve. These findings demonstrate the differential peripheral neuronal mediation of the feeding responses evoked by CCK-8 and CCK-33. PMID:21745513

  14. Myelinated Axons in the Auricular Branch of the Human Vagus Nerve.

    PubMed

    Safi, Sami; Ellrich, Jens; Neuhuber, Winfried

    2016-09-01

    Transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN) resulted in deactivation of temporal lobe structures, similar to invasive cervical vagus nerve (CVN) stimulation. Presumably, both methods stimulated myelinated afferent beta axons mediating anti-convulsive effects. How numbers of A beta axons in the human ABVN compare to those of the CVN is unknown. The ABVN, CVN, recurrent laryngeal nerve (RLN) and thoracic vagus nerve (TVN) were dissected from embalmed bodies. Numbers and calibers of myelinated axons were analyzed in semithin sections. Myelinated axons in the left and right ABVN averaged to 385 and 363, respectively. Numbers of A beta axons measuring ≥7 µm averaged to 64 and 78 on the left and right, respectively. Numbers of A beta axons in CVN were estimated by subtracting myelinated presumed motor axons in RLN from the total count of CVN. This resulted in 280 and 504 A beta axons on the left and right, respectively, concurring well with the thick myelinated axon count of the ipsilateral TVN (255 and 466, respectively). Thus, the ratio of A beta axons in the ABVN and CVN was ∼1:5 and 1:6 on the left and right side, respectively. These results indicate that transcutaneous ABVN stimulation might be a promising alternative to invasive CVN stimulation. Anat Rec, 299:1184-1191, 2016. © 2016 Wiley Periodicals, Inc. PMID:27342906

  15. Optical determination of impulse conduction velocity during development of embryonic chick cervical vagus nerve bundles.

    PubMed Central

    Sakai, T; Komuro, H; Katoh, Y; Sasaki, H; Momose-Sato, Y; Kamino, K

    1991-01-01

    1. Employing an optical method for multiple-site simultaneous recording of electrical activity, we have determined the conduction velocity in cervical vagus nerve bundles isolated from 5- to 21-day-old chick embryos, and investigated its developmental changes. 2. The preparations were stained with a voltage-sensitive merocyanine-rhodanine dye (NK2761), and action potential- (impulse-) related optical signals were elicited by brief stimuli applied to the end of the vagus nerve bundle with a suction electrode. Optical signals were recorded simultaneously from many contiguous regions using a 12 x 12-element photodiode array. 3. The optical signals spread with small delay from the site of stimulation. From the relationship between the delay and distance from the current-applying electrode, conduction velocities were estimated in each tested preparation: the conduction velocity was very small and increased monotonically from about 0.1 m s-1 at 5 days embryonic age to about 0.4 m s-1 by hatching. The increase in the conduction velocity was closely related to a developmental increase in the diameter of the vagus nerve bundle. 4. In addition, we have examined the spread of electrotonic potentials. The space constant was very small (200-450 microns) and increased as development proceeded. 5. Compound optical action signals having two distinct components were also recorded. They often appeared to be concentrated in the preparations from 8- to 12-day-old embryos. The conduction velocity of the second component was slower than that of the first. We suggest that appearance of the second component reflects degeneration of a subset of axons resulting from 'neural cell death' during the development of the vagus nerve. Images Fig. 1 Fig. 14 (cont.) Fig. 14 PMID:1895241

  16. The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans.

    PubMed

    Burger, Andreas M; Verkuil, Bart; Van Diest, Ilse; Van der Does, Willem; Thayer, Julian F; Brosschot, Jos F

    2016-07-01

    A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve enhances memory formation in both animals and humans. The objective of this study was to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess fear conditioning and subsequent fear extinction, we assessed US expectancy ratings, fear potentiated startle responses and phasic heart rate responses. We conducted a randomized controlled trial in thirty-one healthy participants. After fear conditioning participants were randomly assigned to receive tVNS or sham stimulation during the extinction phase. Retention of extinction memory was tested 24h later. tVNS accelerated explicit fear extinction learning (US expectancy ratings), but did not lead to better retention of extinction memory 24h later. We did not find a differential physiological conditioning response during the acquisition of fear and thus were unable to assess potential effects of tVNS on the extinction of physiological indices of fear. These findings complement recent studies that suggest vagus nerve stimulation could be a promising tool to improve memory consolidation and fear extinction. PMID:27222436

  17. Increased Extracellular Concentrations of Norepinephrine in Cortex and Hippocampus Following Vagus Nerve Stimulation in the Rat.

    PubMed Central

    Roosevelt, Rodney W.; Smith, Douglas C.; Clough, Richard W.; Jensen, Robert A.; Browning, Ronald A.

    2006-01-01

    The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no effect on NE concentrations, while the 0.5 mA stimulation increased NE concentrations significantly in the hippocampus (23%), but not the cortex. However, 1.0 mA stimulation significantly increased NE concentrations in both the cortex (39%) and hippocampus (28%) bilaterally. The increases in NE were transient and confined to the stimulation periods. VNS did not alter NE concentrations in either structure during the inter-stimulation baseline periods. No differences were observed between NE levels in the initial baseline and the post-stimulation baselines. These findings support the hypothesis that VNS increases extracellular NE concentrations in both the hippocampus and cortex. PMID:16962076

  18. Excitation properties of the right cervical vagus nerve in adult dogs.

    PubMed

    Castoro, Mark A; Yoo, Paul B; Hincapie, Juan G; Hamann, Jason J; Ruble, Stephen B; Wolf, Patrick D; Grill, Warren M

    2011-01-01

    Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression, and it is currently under investigation for applications in Alzheimer's disease, anxiety, heart failure, and obesity. However, the mechanism(s) by which VNS has its effects are not clear, and the stimulation parameters for obtaining therapeutic outcomes appear highly variable. The purpose of this study was to quantify the excitation properties of the right cervical vagus nerve in adult dogs anesthetized with propofol and fentanyl. Input-output curves of the right cervical vagus nerve compound action potential and laryngeal muscle electromyogram were measured in response to VNS across a range of stimulation parameters: amplitudes of 0.02-50mA, pulsewidths of 10, 50, 100, 200, 300, 500, and 1,000μs, frequencies of 1-2Hz, and train lengths of 20 pulses with 3 different electrode configurations: monopolar cathode, proximal anode/distal cathode, and proximal cathode/distal anode. Electrode configuration and stimulation waveform (monophasic vs. asymmetric charge-balanced biphasic) did not affect the threshold or recruitment of the vagal nerve fibers that were activated. The rheobase currents of A- and B-fibers were 0.4mA and 0.7mA, respectively, and the chronaxie of both components was 180μs. Pulsewidth had little effect on the normalized threshold difference between activation of A- and B-fibers. The results provide insight into the complement of nerve fibers activated by VNS and guidance to clinicians for the selection of optimal stimulation parameters. PMID:20851118

  19. Modulation of heart rate by temporally patterned vagus nerve stimulation in the anesthetized dog.

    PubMed

    Yoo, Paul B; Liu, Haoran; Hincapie, Juan G; Ruble, Stephen B; Hamann, Jason J; Grill, Warren M

    2016-02-01

    Despite current knowledge of the myriad physiological effects of vagus nerve stimulation (VNS) in various mammalian species (including humans), the impact of varying stimulation parameters on nerve recruitment and physiological responses is not well understood. We investigated nerve recruitment, cardiovascular responses, and skeletal muscle responses to different temporal patterns of VNS across 39 combinations of stimulation amplitude, frequency, and number of pulses per burst. Anesthetized dogs were implanted with stimulating and recording cuff electrodes around the cervical vagus nerve, whereas laryngeal electromyogram (EMG) and heart rate were recorded. In seven of eight dogs, VNS-evoked bradycardia (defined as ≥10% decrease in heart rate) was achieved by applying stimuli at amplitudes equal to or greater than the threshold for activating slow B-fibers. Temporally patterned VNS (minimum 5 pulses per burst) was sufficient to elicit bradycardia while reducing the concomitant activation of laryngeal muscles by more than 50%. Temporal patterns of VNS can be used to modulate heart rate while minimizing laryngeal motor fiber activation, and this is a novel approach to reduce the side effects produced by VNS. PMID:26811057

  20. Effects of high-frequency alternating current on axonal conduction through the vagus nerve

    NASA Astrophysics Data System (ADS)

    Waataja, Jonathan J.; Tweden, Katherine S.; Honda, Christopher N.

    2011-10-01

    High-frequency alternating current (HFAC) is known to disrupt axonal conduction in peripheral nerves, and HFAC has much potential as a therapeutic approach for a number of pathological conditions. Many previous studies have utilized motor output as a bioassay of effects of HFAC on conduction through medium- to large-diameter motor axons. However, little is known about the effectiveness of HFAC on smaller, more slowly conducting nerve fibres. The present study tested whether HFAC influences axonal conduction through sub-diaphragmatic levels of the rat vagus nerve, which consists almost entirely of small calibre axons. Using an isolated nerve preparation, we tested the effects of HFAC on electrically evoked compound action potentials (CAPs). We found that delivery of charge-balanced HFAC at 5000 Hz for 1 min was effective in producing reversible blockade of axonal conduction. Both Aδ and C components of the vagus CAP were attenuated, and the degree of blockade as well as time to recovery was proportional to the amount of HFAC current delivered. The Aδ waves were more sensitive than C waves to HFAC blockade, but they required more time to recover.

  1. Effects of high-frequency alternating current on axonal conduction through the vagus nerve.

    PubMed

    Waataja, Jonathan J; Tweden, Katherine S; Honda, Christopher N

    2011-10-01

    High-frequency alternating current (HFAC) is known to disrupt axonal conduction in peripheral nerves, and HFAC has much potential as a therapeutic approach for a number of pathological conditions. Many previous studies have utilized motor output as a bioassay of effects of HFAC on conduction through medium- to large-diameter motor axons. However, little is known about the effectiveness of HFAC on smaller, more slowly conducting nerve fibres. The present study tested whether HFAC influences axonal conduction through sub-diaphragmatic levels of the rat vagus nerve, which consists almost entirely of small calibre axons. Using an isolated nerve preparation, we tested the effects of HFAC on electrically evoked compound action potentials (CAPs). We found that delivery of charge-balanced HFAC at 5000 Hz for 1 min was effective in producing reversible blockade of axonal conduction. Both Aδ and C components of the vagus CAP were attenuated, and the degree of blockade as well as time to recovery was proportional to the amount of HFAC current delivered. The Aδ waves were more sensitive than C waves to HFAC blockade, but they required more time to recover. PMID:21918293

  2. Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.

    2003-01-01

    Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

  3. Vagus Nerve Stimulation to Augment Recovery from Severe Traumatic Brain Injury Impeding Consciousness: A Prospective Pilot Clinical Trial

    PubMed Central

    Shi, Chen; Flanagan, Steven R.; Samadani, Uzma

    2015-01-01

    Objectives Traumatic brain injury has a high morbidity and mortality in both civilian and military populations. Blast and other mechanisms of traumatic brain injury damage the brain by causing neurons to disconnect and atrophy. Such traumatic axonal injury can lead to persistently vegetative and minimally conscious states, for which limited treatment options exist, including physical, occupational, speech and cognitive therapies. More than 60,000 patients have received vagus nerve stimulation for epilepsy and depression. In addition to decreased seizure frequency and severity, patients report enhanced mood, reduced daytime sleepiness independent of seizure control, increased slow wave sleep, and improved cognition, memory, and quality of life. Early stimulation of the vagus nerve accelerates the rate and extent of behavioral and cognitive recovery after fluid percussion brain injury in rats. Methods We recently obtained FDA approval for a pilot prospective randomized crossover trial to demonstrate objective improvement in clinical outcome by placement of a vagus nerve stimulator in patients who are recovering from severe traumatic brain injury. Our hypothesis is that stimulation of the vagus nerve results in increased cerebral blood flow and metabolism in the forebrain, thalamus and reticular formation, which promotes arousal and improved consciousness, thereby improving outcome after traumatic brain injury resulting in minimally conscious or persistent vegetative states. Discussion If this study demonstrates that vagus nerve stimulation can safely and positively impact outcome, then a larger randomized prospective crossover trial will be proposed. PMID:23485054

  4. Chronic vagus nerve stimulation in Crohn's disease: a 6-month follow-up pilot study.

    PubMed

    Bonaz, B; Sinniger, V; Hoffmann, D; Clarençon, D; Mathieu, N; Dantzer, C; Vercueil, L; Picq, C; Trocmé, C; Faure, P; Cracowski, J-L; Pellissier, S

    2016-06-01

    The vagus nerve (VN) is a link between the brain and the gut. The VN is a mixed nerve with anti-inflammatory properties through the activation of the hypothalamic-pituitary-adrenal axis by its afferents and by activating the cholinergic anti-inflammatory pathway through its efferents. We have previously shown that VN stimulation (VNS) improves colitis in rats and that the vagal tone is blunted in Crohn's disease (CD) patients. We thus performed a pilot study of chronic VNS in patients with active CD. Seven patients under VNS were followed up for 6 months with a primary endpoint to induce clinical remission and a secondary endpoint to induce biological (CRP and/or fecal calprotectin) and endoscopic remission and to restore vagal tone (heart rate variability). Vagus nerve stimulation was feasible and well-tolerated in all patients. Among the seven patients, two were removed from the study at 3 months for clinical worsening and five evolved toward clinical, biological, and endoscopic remission with a restored vagal tone. These results provide the first evidence that VNS is feasible and appears as an effective tool in the treatment of active CD. PMID:26920654

  5. Vagus Nerve Stimulation in Ischemic Stroke: Old Wine in a New Bottle

    PubMed Central

    Cai, Peter Y.; Bodhit, Aakash; Derequito, Roselle; Ansari, Saeed; Abukhalil, Fawzi; Thenkabail, Spandana; Ganji, Sarah; Saravanapavan, Pradeepan; Shekar, Chandana C.; Bidari, Sharatchandra; Waters, Michael F.; Hedna, Vishnumurthy Shushrutha

    2014-01-01

    Vagus nerve stimulation (VNS) is currently Food and Drug Administration-approved for treatment of both medically refractory partial-onset seizures and severe, recurrent refractory depression, which has failed to respond to medical interventions. Because of its ability to regulate mechanisms well-studied in neuroscience, such as norepinephrine and serotonin release, the vagus nerve may play an important role in regulating cerebral blood flow, edema, inflammation, glutamate excitotoxicity, and neurotrophic processes. There is strong evidence that these same processes are important in stroke pathophysiology. We reviewed the literature for the role of VNS in improving ischemic stroke outcomes by performing a systematic search for publications in Medline (1966–2014) with keywords “VNS AND stroke” in subject headings and key words with no language restrictions. Of the 73 publications retrieved, we identified 7 studies from 3 different research groups that met our final inclusion criteria of research studies addressing the role of VNS in ischemic stroke. Results from these studies suggest that VNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. Given the lack of success in Phase III trials for stroke neuroprotection, it is important to develop new therapies targeting different neuroprotective pathways. Further studies of the possible role of VNS, through normally physiologically active mechanisms, in ischemic stroke therapeutics should be conducted in both animal models and clinical studies. In addition, recent advent of a non-invasive, transcutaneous VNS could provide the potential for easier clinical translation. PMID:25009531

  6. Chronic vagus nerve stimulation for treatment-resistant depression decreases resting ventromedial prefrontal glucose metabolism

    PubMed Central

    Pardo, José V.; Sheikh, Sohail A.; Schwindt, Graeme C.; Lee, Joel T.; Kuskowski, Michael A.; Surerus, Christa; Lewis, Scott M.; Abuzzahab, Farouk S.; Adson, David E.; Rittberg, Barry R.

    2008-01-01

    Vagus nerve stimulation (VNS) is used as an adjunctive therapy for treatment-resistant depression (TRD). Its mechanism of action is not fully understood. Longitudinal measurement of changes in brain metabolism associated with VNS can provide insights into this new treatment modality. Eight severely depressed outpatients who were highly treatment-resistant underwent electrical stimulation of the left vagus nerve for approximately one year. The main outcome measures were resting regional brain glucose uptake measured with positron emission tomography (PET) and the 24-item Hamilton Depression Scale. The most significant and extensive change over one year of chronic VNS localized to the ventromedial prefrontal cortex extending from the subgenual cingulate to the frontal pole. This region continued to decline in metabolism even toward the end of the study. Clinically, this cohort showed a trend for improvement. No correlations surfaced between change in glucose uptake and depression scores. However, the sample size was small; none remitted; and the range of depression scores was limited. Chronic VNS as adjunctive therapy in patients with severe TRD produces protracted and robust declines in resting brain activity within the ventromedial prefrontal cortex, a network with dense connectivity to the amygdala and structures monitoring the internal milieu. PMID:18595737

  7. Transcutaneous Auricular Vagus Nerve Stimulation Protects Endotoxemic Rat from Lipopolysaccharide-Induced Inflammation

    PubMed Central

    Zhao, Yu Xue; He, Wei; Jing, Xiang Hong; Liu, Jun Ling; Rong, Pei Jing; Ben, Hui; Liu, Kun; Zhu, Bing

    2012-01-01

    Background. Transcutaneous auricular vagus nerve stimulation (ta-VNS) could evoke parasympathetic activities via activating the brainstem autonomic nuclei, similar to the effects that are produced after vagus nerve stimulation (VNS). VNS modulates immune function through activating the cholinergic anti-inflammatory pathway. Methods. VNS, ta-VNS, or transcutaneous electrical acupoint stimulation (TEAS) on ST36 was performed to modulate the inflammatory response. The concentration of serum proinflammatory cytokines and tissue NF-kappa B p65 (NF-κB p65) were detected in endotoxaemia affected anesthetized rats. Results. Similar to the effect of VNS, ta-VNS suppressed the serum proinflammatory cytokines levels, such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as well as NF-kappa B p65 expressions of lung tissues. ST36 stimulation also decreases LPS-induced high TNF-α level and NF-κB signal, but it did not restrain proinflammatory cytokine IL-1β and IL-6. Neither ta-VNS nor ST36 stimulation could suppress LPS-induced TNF-α and NF-κB after vagotomy or with α7nAChR antagonist injection. Conclusions. The present paper demonstrated that ta-VNS could be utilized to suppress LPS-induced inflammatory responses via α7nAChR-mediated cholinergic anti-inflammatory pathway. PMID:23346208

  8. Transcutaneous Vagus Nerve Stimulation (tVNS) does not increase prosocial behavior in Cyberball.

    PubMed

    Sellaro, Roberta; Steenbergen, Laura; Verkuil, Bart; van IJzendoorn, Marinus H; Colzato, Lorenza S

    2015-01-01

    Emerging research suggests that individuals experience vicarious social pain (i.e., ostracism). It has been proposed that observing ostracism increases activity in the insula and in the prefrontal cortex (PFC), two key brain regions activated by directly experiencing ostracism. Here, we assessed the causal role of the insula and PFC in modulating neural activity in these areas by applying transcutaneous Vagus Nerve Stimulation (tVNS), a new non-invasive and safe method to stimulate the vagus nerve that has been shown to activate the insula and PFC. A single-blind, sham-controlled, within-subjects design was used to assess the effect of on-line (i.e., stimulation overlapping with the critical task) tVNS in healthy young volunteers (n = 24) on the prosocial Cyberball game, a virtual ball-tossing game designed to measure prosocial compensation of ostracism. Active tVNS did not increase prosocial helping behavior toward an ostracized person, as compared to sham (placebo) stimulation. Corroborated by Bayesian inference, we conclude that tVNS does not modulate reactions to vicarious ostracism, as indexed by performance in a Cyberball game. PMID:25972825

  9. Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings.

    PubMed

    Labiner, David M; Ahern, Geoffrey L

    2007-01-01

    Vagus nerve stimulation (VNS) therapy is an effective adjunctive treatment for chronic or recurrent treatment-resistant depression in adults, and for pharmacoresistant epilepsy in adults and adolescents. VNS therapy is administered through an implanted pulse generator that delivers programmed electrical pulses through an implanted lead to the left vagus nerve. Programmable pulse parameters include output current, frequency, pulse width, and ON/OFF times. Within a range of typical values, individual patients respond best to different combinations of parameter settings. The physician must identify the optimum settings for each patient while balancing the goals of maximizing efficacy, minimizing side effects, and preserving battery life. Output current is gradually increased from 0.25 mA to the maximum tolerable level (maximum, 3.5 mA); typical therapeutic settings range from 1.0 to 1.5 mA. Greater output current is associated with increased side effects, including voice alteration, cough, a feeling of throat tightening, and dyspnea. Frequency is typically programmed at 20 Hz in depression and 30 Hz in epilepsy. Pulse width is typically 250 or 500 micros. The recommended initial ON time is 30 s, followed by 5 min OFF; OFF time > ON time is recommended. As with pharmacotherapy, VNS therapy must be adjusted in a gradual, systematic fashion to individualize therapy for each patient. PMID:17156262

  10. Vagus nerve stimulation for treatment of partial seizures: 2. Safety, side effects, and tolerability. First International Vagus Nerve Stimulation Study Group.

    PubMed

    Ramsay, R E; Uthman, B M; Augustinsson, L E; Upton, A R; Naritoku, D; Willis, J; Treig, T; Barolat, G; Wernicke, J F

    1994-01-01

    Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device. We also reviewed potential drug interactions, device output complications, and impact of the therapy on overall health status. We analyzed the first 67 patients to exist the acute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Data were collected from case report forms used at each of the four visits during the 12-week baseline and at each of the four visits during the 14-week randomized phase of the trial. No significant complications were reported as a result of the implant procedure. Serious adverse events included 1 patient who experienced direct current to the vagus nerve owing to generator malfunction resulting in left vocal cord paralysis and withdrawal of the patient from the study. No clinically significant effects on vital signs, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group were hoarseness (35.5%), coughing (13.9%), and throat pain (12.9%). In the low group, only hoarseness (13.9%) and throat pain (13.9%) were associated with VNS. These effects generally wrre not considered clinically significant and occurred primarily during the stimulation pulses. No patients discontinued VNS therapy during the acute phase because of side effects associated with normal stimulation. Except for the one instance of a short circuit in the system resulting in a direct current, stimulating system complications were minor, limited to programming, unscheduled stimulation, and high lead impedance. Patients, investigators, and patient companions rated patients receiving high stimulation as more "improved" than those receiving low stimulation in regards to overall health status. Antiepileptic drug (AED) plasma

  11. Peripheral vagus nerve stimulation significantly affects lipid composition and protein secondary structure within dopamine-related brain regions in rats.

    PubMed

    Surowka, Artur Dawid; Krygowska-Wajs, Anna; Ziomber, Agata; Thor, Piotr; Chrobak, Adrian Andrzej; Szczerbowska-Boruchowska, Magdalena

    2015-06-01

    Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders. PMID:25893743

  12. Cannabinoid Receptor 1 in the Vagus Nerve Is Dispensable for Body Weight Homeostasis But Required for Normal Gastrointestinal Motility

    PubMed Central

    Vianna, Claudia R.; Donato, Jose; Rossi, Jari; Scott, Michael; Economides, Kyriakos; Gautron, Lauren; Pierpont, Stephanie; Elias, Carol F.; Elmquist, Joel K.

    2016-01-01

    The cannabinoid receptor 1 (CB1R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB1R that regulate these physiological functions are unknown. CB1R is widely expressed, including in neurons of the parasympathetic branches of the autonomic nervous system. The vagus nerve has been implicated in the regulation of several aspects of metabolism and energy balance (e.g., food intake and glucose balance), and gastrointestinal functions including motility. To directly test the relevance of CB1R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB1R in afferent and efferent branches of the vagus nerve (Cnr1flox/flox; Phox2b–Cre mice). On a chow or on a high-fat diet, Cnr1flox/flox; Phox2b–Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1flox/flox control mice. Also, fasting-induced hyperphagia and after acute or chronic pharmacological treatment with SR141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide] (CB1R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1flox/flox; Phox2b–Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB1R in the vagus nerve as a key component underlying normal gastrointestinal motility. PMID:22836266

  13. Vagus Nerve Stimulation Increases Energy Expenditure: Relation to Brown Adipose Tissue Activity

    PubMed Central

    Vijgen, Guy H. E. J.; Bouvy, Nicole D.; Leenen, Loes; Rijkers, Kim; Cornips, Erwin; Majoie, Marian; Brans, Boudewijn; van Marken Lichtenbelt, Wouter D.

    2013-01-01

    Background Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. Methods and Findings Fifteen patients with stable VNS therapy (age: 45±10yrs; body mass index; 25.2±3.5 kg/m2) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUVMean; 0.55±0.25 versus 0.67±0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). Conclusions VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. Trial Registration The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282. PMID:24194874

  14. Early experiences with tachycardia-triggered vagus nerve stimulation using the AspireSR stimulator.

    PubMed

    El Tahry, Riëm; Hirsch, Martin; Van Rijckevorsel, Kenou; Santos, Susana Ferrao; de Tourtchaninoff, Marianne; Rooijakkers, Herbert; Coenen, Volker; Schulze-Bonhage, Andreas

    2016-06-01

    Many epilepsy patients treated with vagus nerve stimulation additionally use an "on-demand" function, triggering an extra stimulation to terminate a seizure or diminish its severity. Nevertheless, a substantial number of patients are not able to actively trigger stimulations by use of a magnet, due to the absence of an aura or inability for voluntary actions in the early phase of a seizure. To address this need, a novel implantable pulse generator, the AspireSR VNS system, was developed to provide automated ictal stimulation triggered by a seizure-detecting algorithm. We report our experience with three patients in assessing the functionality of ictal stimulation, illustrating the detection system in practice. Detection of ictal tachycardia and variable additional detections of physiological tachycardia depended on the individual seizure-detecting algorithm settings. PMID:27248796

  15. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

    PubMed

    Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

    2013-12-01

    Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. PMID:23954448

  16. Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve.

    PubMed

    Yoo, Paul B; Hincapie, Juan G; Hamann, Jason J; Ruble, Stephen B; Wolf, Patrick D; Grill, Warren M

    2011-01-01

    Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy. PMID:22254997

  17. The therapeutic dilemma of vagus nerve stimulator-induced sleep disordered breathing

    PubMed Central

    Upadhyay, Hinesh; Bhat, Sushanth; Gupta, Divya; Mulvey, Martha; Ming, Sue

    2016-01-01

    Intermittent vagus nerve stimulation (VNS) can reduce the frequency of seizures in patients with refractory epilepsy, but can affect respiration in sleep. Untreated obstructive sleep apnea (OSA) can worsen seizure frequency. Unfortunately, OSA and VNS-induced sleep disordered breathing (SDB) may occur in the same patient, leading to a therapeutic dilemma. We report a pediatric patient in whom OSA improved after tonsillectomy, but coexistent VNS-induced SDB persisted. With decrease in VNS output current, patient's SDB improved, but seizure activity exacerbated, which required a return to the original settings. Continuous positive airway pressure titration was attempted, which showed only a partial improvement in apnea–hypopnea index. This case illustrates the need for clinicians to balance seizure control and SDB in patients with VNS. PMID:27168865

  18. The therapeutic dilemma of vagus nerve stimulator-induced sleep disordered breathing.

    PubMed

    Upadhyay, Hinesh; Bhat, Sushanth; Gupta, Divya; Mulvey, Martha; Ming, Sue

    2016-01-01

    Intermittent vagus nerve stimulation (VNS) can reduce the frequency of seizures in patients with refractory epilepsy, but can affect respiration in sleep. Untreated obstructive sleep apnea (OSA) can worsen seizure frequency. Unfortunately, OSA and VNS-induced sleep disordered breathing (SDB) may occur in the same patient, leading to a therapeutic dilemma. We report a pediatric patient in whom OSA improved after tonsillectomy, but coexistent VNS-induced SDB persisted. With decrease in VNS output current, patient's SDB improved, but seizure activity exacerbated, which required a return to the original settings. Continuous positive airway pressure titration was attempted, which showed only a partial improvement in apnea-hypopnea index. This case illustrates the need for clinicians to balance seizure control and SDB in patients with VNS. PMID:27168865

  19. [Interaction of abdominal vagus and greater splanchnic nerve activities in the nucleus tractus solitarius of the rabbit].

    PubMed

    Zhang, J; Huang, Z S

    1990-12-01

    Experiments were performed on 67 rabbits. Effects of stimulation of the central ends of abdominal vagus and greater splanchnic nerve on arterial blood pressure before and after destruction of nucleus tractus solitarius (NTS) and the unit discharges in the NTS before destruction were observed. As a result, we suggest that both the afferents coming from the abdominal vagus and greater splanchnic nerve not only converge on NTS neurons but also interact with each other. Subthreshold stimulation elicited from one of the afferent fibers suppresses the arterial blood pressure responses caused by the other afferent. Similarly, background stimulation elicited from one afferent can suppress the NTS unit discharges caused by the other afferent. It is much easier for abdominal vagal afferent to inhibit the NTS unit discharges and the arterial blood pressure changes elicited by stimulation of the splanchnic nerve. A possible mechanism of such relationship was discussed. PMID:2293366

  20. Characterization of the anandamide induced depolarization of guinea-pig isolated vagus nerve

    PubMed Central

    Kagaya, Manabu; Lamb, Jasmine; Robbins, Jon; Page, Clive P; Spina, Domenico

    2002-01-01

    There is considerable interest in elucidating potential endogenously derived agonists of the vanilloid receptor and the role of anandamide in this regard has received considerable attention. In the present study, we have used an electrophysiological technique to investigate the mechanism of activation of vanilloid receptors in an isolated vagal preparation. Both capsaicin and anandamide depolarized de-sheathed whole vagal nerve preparations that was antagonized by the VR1 antagonist, capsazepine (P<0.05) whilst this response was unaltered by the cannabinoid (CB1) selective antagonist SR141716A or the CB2 selective antagonist, SR144528, thereby ruling out a role for cannabinoid receptors in this response. The PKC activator, phorbol-12-myristate-13-acetate (PMA) augmented depolarization to both anandamide and capsaicin and this response was significantly inhibited with the PKC inhibitor, bisindolylmaleimide (BIM) (P<0.05). The role of lipoxygenase products in the depolarization to anandamide was investigated in the presence of the lipoxygenase inhibitor, 5,8,11-Eicosatriynoic acid (ETI). Depolarization to anandamide and arachidonic acid was significantly inhibited in the presence of ET1 (P<0.05). However, in the absence of calcium depolarization to anandamide was not inhibited by ETI. Using confocal microscopy we have demonstrated the presence of vanilloid receptors on both neuropeptide containing nerves and nerves that did not stain for sensory neuropeptides. These results demonstrate that anandamide evokes depolarization of guinea-pig vagus nerve, following activation of vanilloid receptors, a component of which involves the generation of lipoxygenase products. Furthermore, these receptors are distributed in both neuropeptide and non-neuropeptide containing nerves. PMID:12183329

  1. Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial

    PubMed Central

    2012-01-01

    Background Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response. This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. Design One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. Discussion This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical

  2. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

    PubMed

    Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2015-10-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions. PMID:26276818

  3. ELECTRICAL STIMULATION OF THE VAGUS NERVE DERMATOME IN THE EXTERNAL EAR IS PROTECTIVE IN RAT CEREBRAL ISCHEMIA

    PubMed Central

    Ay, Ilknur; Napadow, Vitaly; Ay, Hakan

    2014-01-01

    Background Although cervical vagus nerve stimulation is effective for reducing infarct volume in rats, it is not feasible for acute human stroke as it requires surgical incision of the neck. We hypothesized that stimulation of the dermatome in the external ear innervated by the vagus nerve (auricular vagus nerve stimulation; aVNS) reduces infarct volume after transient focal ischemia in rats. Methods Animals were randomized to active aVNS or sham stimulation. For aVNS, electrical stimulation of the left cavum concha (1 hour duration) using percutaneous needles was initiated 30 min after induction of ischemia. Behavioral and tissue outcome were measured 24 hours after induction of ischemia. In a separate experimental dataset, c-Fos immunohistochemistry was performed to identify the brain regions activated after the stimulation. Results Stimulation of the left cavum concha resulted in bilateral c-Fos staining in the nuclei tractus solitarii and the loci coerulei in all animals. There was no c-Fos staining in any part of the brainstem in sham control animals. The mean infarct volume (SD) as calculated by indirect method was 44.20 ± 7.58% in controls and 31.65 ± 9.67% in treated animals (p<0.0001). The effect of aVNS on tissue outcome was associated with better neurological scores at 24 hours after ischemia (p<0.0001). Conclusions Electric stimulation of the vagus nerve dermatome in the external ear activates brainstem afferent vagal nuclei and reduces infarct volume in rats. This finding has potential to facilitate the development of treatments that leverage the brain’s endogenous neuroprotective pathways at the setting of acute ischemic stroke. PMID:25312600

  4. Episodic phrenic-inhibitory vagus nerve stimulation paradoxically induces phrenic long-term facilitation in rats

    PubMed Central

    Zhang, Yi; McGuire, Michelle; White, David P; Ling, Liming

    2003-01-01

    All respiratory long-term facilitation (LTF) is induced by inspiratory-excitatory stimulation, suggesting that LTF needs inspiratory augmentation and is the result of a Hebbian mechanism (coincident pre- and post-synaptic activity strengthens synapses). The present study examined the long-term effects of episodic inspiratory-inhibitory vagus nerve stimulation (VNS) on phrenic nerve activity. We hypothesized that episodic VNS would induce phrenic long-term depression. The results are compared with those obtained following serotonin receptor antagonism or episodic carotid sinus nerve stimulation (CSNS). Integrated phrenic neurograms were measured before, during and after three episodes of 5 min VNS (50 Hz, 0.1 ms), each separated by a 5 min interval, at a low (˜50 μA), medium (˜200 μA) or high (˜500 μA) stimulus intensity in anaesthetized, vagotomized, neuromuscularly blocked and artificially ventilated rats. Medium- and high-intensity VNS eliminated rhythmic phrenic activity during VNS, while low-intensity VNS only reduced phrenic burst frequency. At 60 min post-VNS, phrenic amplitude was higher than baseline (35 ± 5 % above baseline, mean ± S.E.M., P < 0.05) in the high-intensity group but not in the low- (−4 ± 4 %) or medium-intensity groups (−10 ± 15 %), or in the high-intensity with methysergide group (4 mg kg−1, I.P.) (−11 ± 5 %). These data, which are inconsistent with our hypothesis, indicate that phrenic-inhibitory VNS induces a serotonin-dependent phrenic LTF similar to that induced by phrenic-excitatory CSNS (33 ± 7 %) and may require activation of high-threshold afferent fibres. These data also suggest that the synapses on phrenic motoneurons do not use the Hebbian mechanism in this LTF, as these motoneurons were suppressed during VNS. PMID:12872010

  5. Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study

    PubMed Central

    2014-01-01

    Background Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. Methods In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). Results 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients

  6. Signal space separation algorithm and its application on suppressing artifacts caused by vagus nerve stimulation for magnetoencephalography recordings.

    PubMed

    Song, Tao; Cui, Li; Gaa, Kathleen; Feffer, Lori; Taulu, Samu; Lee, Roland R; Huang, Mingxiong

    2009-12-01

    Magnetoencephalography (MEG) has been successfully applied to presurgical epilepsy foci localization and brain functional mapping. Because the neuronal magnetic signals from the brain are extremely weak, MEG measurement requires both low environment noise and the subject/patient being free of artifact-generating metal objects. This strict requirement makes it hard for patients with vagus nerve stimulator, or other similar medical devices, to benefit from the presurgical MEG examinations. Therefore, an approach that can effectively reduce the environmental noise and faithfully recover the brain signals is highly desirable. We applied spatiotemporal signal space separation method, an advanced signal processing approach that can recover bio-magnetic signal from inside the MEG sensor helmet and suppress external disturbance from outside the helmet in empirical MEG measurements, on MEG recordings from normal control subjects and patients who has vagus nerve stimulator. The original MEG recordings were heavily contaminated, and the data could not be assessed. After applying temporal signal space separation, the strong external artifacts from outside the brain were successfully removed, and the neuronal signal from the human brain was faithfully recovered. Both of the goodness-of-fit and 95% confident limit volume confirmed the significant improvement after temporal signal space separation. Hence, temporal signal space separation makes presurgical MEG examinations possible for patients with implanted vagus nerve stimulator or similar medical devices. PMID:19952563

  7. Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve

    PubMed Central

    Lim, Hee-Don; Kim, Min-Hee; Lee, Chan-Yong; Namgung, Uk

    2016-01-01

    Although acupuncture therapy is widely used in traditional Asian medicine for the treatment of diverse internal organ disorders, its underlying biological mechanisms are largely unknown. Here, we investigated the functional involvement of acupuncture stimulation (AS) in the regulation of inflammatory responses. TNF-α production in mouse serum, which was induced by lipopolysaccharide (LPS) administration, was decreased by manual acupuncture (MAC) at the zusanli acupoint (stomach36, ST36). In the spleen, TNF-α mRNA and protein levels were also downregulated by MAC and were recovered by using a splenic neurectomy and a vagotomy. c-Fos, which was induced in the nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMV) by LPS and electroacupuncture (EAC), was further increased by focal administration of the AMPA receptor blocker CNQX and the purinergic receptor antagonist PPADS. TNF-α levels in the spleen were decreased by CNQX and PPADS treatments, implying the involvement of inhibitory neuronal activity in the DVC. In unanesthetized animals, both MAC and EAC generated c-Fos induction in the DVC neurons. However, MAC, but not EAC, was effective in decreasing splenic TNF-α production. These results suggest that the therapeutic effects of acupuncture may be mediated through vagal modulation of inflammatory responses in internal organs. PMID:26991319

  8. Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning.

    PubMed

    Childs, Jessica E; Alvarez-Dieppa, Amanda C; McIntyre, Christa K; Kroener, Sven

    2015-01-01

    Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory. PMID:26325100

  9. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats

    PubMed Central

    Samniang, Bencharunan; Shinlapawittayatorn, Krekwit; Chunchai, Titikorn; Pongkan, Wanpitak; Kumfu, Sirinart; Chattipakorn, Siriporn C.; KenKnight, Bruce H.; Chattipakorn, Nipon

    2016-01-01

    Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats. PMID:26830020

  10. Vagus Nerve Stimulation during Rehabilitative Training Improves Functional Recovery after Intracerebral Hemorrhage

    PubMed Central

    Hays, Seth A.; Khodaparast, Navid; Hulsey, Daniel R.; Ruiz, Andrea; Sloan, Andrew M.; Rennaker, Robert L.; Kilgard, Michael P.

    2014-01-01

    Background and Purpose Vagus nerve stimulation (VNS) delivered during rehabilitative training enhances neuroplasticity and improves recovery in models of cortical ischemic stroke. However, VNS therapy has not been applied in a model of subcortical intracerebral hemorrhage (ICH). We hypothesized that VNS paired with rehabilitative training after ICH would enhance recovery of forelimb motor function beyond rehabilitative training alone. Methods Rats were trained to perform an automated, quantitative measure of forelimb function. Once proficient, rats received an intrastriatal injection of bacterial collagenase to induce ICH. Rats then underwent VNS paired with rehabilitative training (VNS+Rehab; N = 14) or rehabilitative training without VNS (Rehab; N = 12). Rehabilitative training began at least 9 days after ICH and continued for 6 weeks. Results VNS paired with rehabilitative training significantly improved recovery of forelimb function compared to rehabilitative training without VNS. The VNS+Rehab group displayed a 77% recovery of function, while the Rehab group only exhibited 29% recovery. Recovery was sustained after cessation of stimulation. Both groups performed similar amounts of trials during rehabilitative and lesion size was not different between groups. Conclusions VNS paired with rehabilitative training confers significantly improved forelimb recovery following ICH compared to rehabilitative training without VNS. PMID:25147331

  11. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury.

    PubMed

    Neren, Daniel; Johnson, Matthew D; Legon, Wynn; Bachour, Salam P; Ling, Geoffrey; Divani, Afshin A

    2016-04-01

    The objective of this paper is to review the current literature regarding the use of vagus nerve stimulation (VNS) in preclinical models of traumatic brain injury (TBI) as well as discuss the potential role of VNS along with alternative neuromodulation approaches in the treatment of human TBI. Data from previous studies have demonstrated VNS-mediated improvement following TBI in animal models. In these cases, VNS was observed to enhance motor and cognitive recovery, attenuate cerebral edema and inflammation, reduce blood brain barrier breakdown, and confer neuroprotective effects. Yet, the underlying mechanisms by which VNS enhances recovery following TBI remain to be fully elucidated. Several hypotheses have been offered including: a noradrenergic mechanism, reduction in post-TBI seizures and hyper-excitability, anti-inflammatory effects, attenuation of blood-brain barrier breakdown, and cerebral edema. We present other potential mechanisms by which VNS acts including enhancement of synaptic plasticity and recruitment of endogenous neural stem cells, stabilization of intracranial pressure, and interaction with the ghrelin system. In addition, alternative methods for the treatment of TBI including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation, and focused ultrasound stimulation are discussed. Although the primary source data show that VNS improves TBI outcomes, it remains to be determined if these findings can be translated to clinical settings. PMID:26399249

  12. Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve.

    PubMed

    Lim, Hee-Don; Kim, Min-Hee; Lee, Chan-Yong; Namgung, Uk

    2016-01-01

    Although acupuncture therapy is widely used in traditional Asian medicine for the treatment of diverse internal organ disorders, its underlying biological mechanisms are largely unknown. Here, we investigated the functional involvement of acupuncture stimulation (AS) in the regulation of inflammatory responses. TNF-α production in mouse serum, which was induced by lipopolysaccharide (LPS) administration, was decreased by manual acupuncture (MAC) at the zusanli acupoint (stomach36, ST36). In the spleen, TNF-α mRNA and protein levels were also downregulated by MAC and were recovered by using a splenic neurectomy and a vagotomy. c-Fos, which was induced in the nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus nerve (DMV) by LPS and electroacupuncture (EAC), was further increased by focal administration of the AMPA receptor blocker CNQX and the purinergic receptor antagonist PPADS. TNF-α levels in the spleen were decreased by CNQX and PPADS treatments, implying the involvement of inhibitory neuronal activity in the DVC. In unanesthetized animals, both MAC and EAC generated c-Fos induction in the DVC neurons. However, MAC, but not EAC, was effective in decreasing splenic TNF-α production. These results suggest that the therapeutic effects of acupuncture may be mediated through vagal modulation of inflammatory responses in internal organs. PMID:26991319

  13. Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

    PubMed Central

    Childs, Jessica E.; Alvarez-Dieppa, Amanda C.; McIntyre, Christa K.; Kroener, Sven

    2015-01-01

    Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory. PMID:26325100

  14. Corpus callosotomy versus vagus nerve stimulation for atonic seizures and drop attacks: A systematic review.

    PubMed

    Rolston, John D; Englot, Dario J; Wang, Doris D; Garcia, Paul A; Chang, Edward F

    2015-10-01

    Atonic seizures are debilitating and poorly controlled with antiepileptic medications. Two surgical options are primarily used to treat medically refractory atonic seizures: corpus callosotomy (CC) and vagus nerve stimulation (VNS). However, given the uncertainty regarding relative efficacy and surgical complications, the best approach for affected patients is unclear. The PubMed database was queried for all articles describing the treatment of atonic seizures and drop attacks with either corpus callosotomy or VNS. Rates of seizure freedom, >50% reduction in seizure frequency, and complications were compared across the two patient groups. Patients were significantly more likely to achieve a >50% reduction in seizure frequency with CC versus VNS (85.6% versus 57.6%; RR: 1.5; 95% CI: 1.1-2.1). Adverse events were more common with VNS, though typically mild (e.g., 22% hoarseness and voice changes), compared with CC, where the most common complication was the disconnection syndrome (13.2%). Both CC and VNS are well tolerated for the treatment of refractory atonic seizures. Existing studies suggest that CC is potentially more effective than VNS in reducing seizure frequency, though a direct study comparing these techniques is required before a definitive conclusion can be reached. PMID:26247311

  15. Vagus nerve stimulation in treating depression: A tale of two stories.

    PubMed

    Yuan, T-F; Li, A; Sun, X; Arias-Carrión, O; Machado, S

    2016-01-01

    Vagus nerve stimulation (VNS) has been widely used to treat different neurological disorders, especially epilepsy. Accumulating evidence also suggests its potential application in antidepressive therapy, given that VNS has been confirmed by several clinical trials to exert long-term effects on mitigating depression and reducing the risk of relapse in depressed patients. Likewise, VNS has also proven to ameliorate the behavioral deficits in a rat model of depression. While the influences of VNS on monoamine metabolism and mood improvement are well-recognized, the underlying mechanisms mediating its antidepressive action remain poorly understood. Recent findings suggest that VNS-enhanced proliferation of hippocampal neural progenitor cells (NPCs) and synaptic transmission might serve as a monoamine-independent pathway contributive to the beneficial effects of VNS on depression. Here we briefly reviewed the recent progress in this field, based on which we propose that there might be, at least, two little-overlapped, and yet interactive pathways mediating the antidepressive action of VNS. PMID:26695696

  16. Biclustering EEG data from epileptic patients treated with vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Busygin, Stanislav; Boyko, Nikita; Pardalos, Panos M.; Bewernitz, Michael; Ghacibeh, Georges

    2007-11-01

    We present a pilot study of an application of consistent biclustering to analyze scalp EEG data obtained from epileptic patients undergoing treatment with a vagus nerve stimulator (VNS). The ultimate goal of this study is to develop a physiologic marker for optimal VNS parameters (e.g. output current, signal frequency, etc.) using measures of scalp EEG signals. A time series of STLmax values was computed for each scalp EEG channel recorded from two epileptic patients and used as a feature of the two datasets. The averaged samples from stimulation periods were then separated from averaged samples from non-stimulation periods by feature selection performed within the consistent biclustering routine. The obtained biclustering results allow us to assume that signals from certain parts of the brain consistently change their characteristics when VNS is switched on and could provide a basis for desirable VNS stimulation parameters. A physiologic marker of optimal VNS effect could greatly reduce the cost, time, and risk of calibrating VNS stimulation parameters in newly implanted patients compared to the current method of clinical response.

  17. Optimal Vagus Nerve Stimulation Frequency for Suppression of Spike-and-Wave Seizures in Rats.

    PubMed

    Jiao, Jianhang; Harreby, Kristian R; Sevcencu, Cristian; Jensen, Winnie

    2016-06-01

    Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug-resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10-30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike-and-wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9-21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130-180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today. PMID:26713661

  18. Electrical Stimulation of the Vagus Nerve Enhances Cognitive and Motor Recovery following Moderate Fluid Percussion Injury in the Rat

    PubMed Central

    SMITH, DOUGLAS C.; MODGLIN, ARLENE A.; ROOSEVELT, RODNEY W.; NEESE, STEVEN L.; JENSEN, ROBERT A.; BROWNING, RONALD A.; CLOUGH, RICHARD W.

    2006-01-01

    Intermittent, chronically delivered electrical stimulation of the vagus nerve (VNS) is an FDA-approved procedure for the treatment of refractory complex/partial epilepsy in humans. Stimulation of the vagus has also been shown to enhance memory storage processes in laboratory rats and human subjects. Recent evidence suggests that some of these effects of VNS may be due to the activation of neurons in the nucleus locus coeruleus resulting in the release of norepinephrine (NE) throughout the neuraxis. Because antagonism of NE systems has been shown to delay recovery of function following brain damage, it is possible that enhanced release of NE in the CNS may facilitate recovery of function. To evaluate this hypothesis the lateral fluid percussion injury (LFP) model of traumatic brain injury was used and a variety of motor and cognitive behavioral tests were employed to assess recovery in pre-trained stimulated, control, and sham-injured laboratory rats. Two hours following moderate LFP, vagus nerve stimulation (30.0-sec trains of 0.5 mA, 20.0 Hz, biphasic pulses) was initiated. Stimulation continued in each animal’s home cage at 30-min intervals for a period of 14 days, with the exception of brief periods when the animals were disconnected for behavioral assessments. Motor behaviors were evaluated every other day following LFP and tests included beam walk, locomotor placing, and skilled forelimb reaching. In each measure an enhanced rate of recovery and/or level of final performance was observed in the VNS-LFP animals compared to non-stimulated LFP controls. Behavior in the Morris water maze was assessed on days 11–14 following injury. Stimulated LFP animals showed significantly shorter latencies to find the hidden platform than did controls. Despite these behavioral effects, neurohistological examination did not reveal significant differences in lesion extent, density of fluorojade positive neurons, reactive astrocytes or numbers of spared neurons in the CA3

  19. [A Case of Left Vertebral Artery Aneurysm Showing Evoked Potentials on Bilateral Electrode by the Left Vagus Nerve Stimulation to Electromyographic Tracheal Tube].

    PubMed

    Kadoya, Tatsuo; Uehara, Hirofumi; Yamamoto, Toshinori; Shiraishi, Munehiro; Kinoshita, Yuki; Joyashiki, Takeshi; Enokida, Kengo

    2016-02-01

    Previously, we reported a case of brainstem cavernous hemangioma showing false positive responses to electromyographic tracheal tube (EMG tube). We concluded that the cause was spontaneous respiration accompanied by vocal cord movement. We report a case of left vertebral artery aneurysm showing evoked potentials on bilateral electrodes by the left vagus nerve stimulation to EMG tube. An 82-year-old woman underwent clipping of a left unruptured vertebral artery-posterior inferior cerebellar artery aneurysm. General anesthesia was induced with remifentanil, propofol and suxamethonium, and was maintained with oxygen, air, remifentanil and propofol. We monitored somatosensory evoked potentials, motor evoked potentials, and electromyogram of the vocal cord. When the manipulation reached brainstem and the instrument touched the left vagus nerve, evoked potentials appeared on bilateral electrodes. EMG tube is equipped with two electrodes on both sides. We concluded that the left vagus nerve stimulation generated evoked potentials of the left laryngeal muscles, and they were simultaneously detected as potential difference between two electrodes on both sides. EMG tube is used to identify the vagus nerve. However, it is necessary to bear in mind that each vagus nerve stimulation inevitably generates evoked potentials on bilateral electrodes. PMID:27017772

  20. Intragastric monosodium L-glutamate stimulates motility of upper gut via vagus nerve in conscious dogs.

    PubMed

    Toyomasu, Yoshitaka; Mochiki, Erito; Yanai, Mitsuhiro; Ogata, Kyoichi; Tabe, Yuichi; Ando, Hiroyuki; Ohno, Tetsuro; Aihara, Ryuusuke; Zai, Hiroaki; Kuwano, Hiroyuki

    2010-04-01

    Monosodium l-glutamate (MSG) is a substance known to produce the umami taste. Recent studies indicate that MSG also stimulates a variety of activities in the gastrointestinal tract through its receptor in the gut, but no study has reported the activity in conscious large experimental animals. The aim of our study was to investigate whether direct intragastric MSG stimulates gut motility and to identify the mechanism in conscious dogs. Contractile response to intraluminal injection of MSG was studied in the fed and fasted states by means of chronically implanted force transducers. MSG (5, 15, 45, and 90 mM/kg) dissolved in water was injected into the stomach and duodenum in normal and vagotomized dogs. MSG solution was administered into the stomach before feeding, and gastric emptying was evaluated. Several inhibitors of gastrointestinal motility (atropine, hexamethonium, and granisetron) were injected intravenously before MSG administration to the stomach. The effect of MSG was investigated in Pavlov (vagally innervated corpus pouch), Heidenhain (vagally denervated corpus pouch), and antral pouch (vagally innervated) dogs. Upper gut motility was significantly increased by intragastric MSG but not significantly stimulated by intraduodenal MSG. Intragastric MSG (45 mM/kg) stimulated postprandial motility and accelerated gastric emptying. MSG-induced contractions were inhibited by truncal vagotomy, atropine, hexamethonium, and granisetron. Gut motility was increased by intrapouch injection of MSG in the Pavlov pouch, but it was not affected in the Heidenhain or antral pouch dogs. We conclude that intragastric MSG stimulates upper gut motility and accelerates gastric emptying. The sensory structure of MSG is present in the gastric corpus, and the signal is mediated by the vagus nerve. PMID:20071606

  1. Vagus nerve stimulation therapy for pharmacoresistant epilepsy: effect on health care utilization.

    PubMed

    Bernstein, Allan L; Hess, Terry

    2007-02-01

    We retrospectively analyzed the effects of vagus nerve stimulation (VNS) therapy on utilization of medical services by 138 patients in a large staff-model health maintenance organization. We compared average quarterly rates for 12 months before device implantation with quarterly rates during 48 months of follow-up. Wilcoxon matched-pairs signed-ranks tests comparing pre-VNS with post-VNS utilization rates showed statistically significant reductions in numbers of emergency department visits, hospitalizations, and hospital lengths of stay, beginning with the first quarter after implantation (P<0.05 for all post-implantation quarters for these three aspects). For the first two quarters after implantation, the average number of outpatient visits was significantly greater than the pre-implant quarterly average (quarter 1: P<0.0001; quarter 2: P=0.0067), but the average was 12.2% less by the fourth quarter of the first year after implantation and significantly less beginning with the first quarter of the second year (P=0.0017) and continuing through the end of the study (P<0.0001 for all subsequent quarters). A comparison of time spent on epilepsy-related tasks during the year before implantation with the year after implantation also revealed significant decreases in the average number of days on which patients could not work because of health-related concerns, from 3.67 to 1.04 days (P=0.002, paired Student's t test) and the average time spent caring for health problems, from 352.6 to 136.1 minutes per week (P<0.001). VNS therapy had a positive effect on both the utilization of health care services and the time spent on epilepsy-related tasks for these patients with pharmacoresistant epilepsy. PMID:17084676

  2. Vagus Nerve Stimulation Reduces Body Weight and Fat Mass in Rats

    PubMed Central

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Marrosu, Francesco; Puligheddu, Monica; Floris, Gabriele; Asuni, Gino Paolo; Cappai, Angela Letizia; Deriu, Silvia; Follesa, Paolo

    2012-01-01

    Among the manifold effects of vagus nerve stimulation (VNS) delivered as an add-on treatment to patients with drug-resistant epilepsy, a moderate loss of body weight has been observed in some individuals. We have now investigated this effect in rats. Exposure of rats to VNS for 4 weeks reduced feed conversion efficiency as well as body weight gain (by ∼25%) and the amount of mesenteric adipose tissue (by ∼45%) in comparison with those in sham-operated control animals. A pair-fed experiment showed that both lower dietary intake and increase energy expenditure independently contributed to the reduction of body weight and mesenteric adipose tissue. Moreover, VNS increased the level of non-esterified fatty acids in plasma and mesenteric adipose tissue by ∼50 and 80%, respectively, without affecting that in the liver. In addition, VNS reduced the amounts of endocannabinoids and increased N-palmitoylethanolamide, an endogenous ligand of the transcription factor PPARα (peroxisome proliferator–activated receptor α) in mesenteric adipose tissue but not in the hypothalamus. These effects were accompanied by increased expression of the gene for brain-derived neurotrophic factor (BDNF) in the hypothalamus and up-regulation of the abundance of PPARα in the liver. Our results suggest that the reduction in body fat induced by VNS in rats may result from the action of both central and peripheral mediators. The reduced feed conversion efficiency associated with VNS may be mediated by hypothalamic BDNF, down-regulation of endocannabinoid tone in mesenteric adipose tissue and a PPARα-dependent increase in fatty acid oxidation in the liver, which in concerted action may account for the anorexic effect and increased energy expenditure. PMID:23028630

  3. Vagus nerve stimulator stability and interference on radiation oncology x-ray beams.

    PubMed

    Gossman, Michael S; Ketkar, Amruta; Liu, Arthur K; Olin, Bryan

    2012-10-21

    Five different models of Cyberonics, Inc. vagus nerve stimulation (VNS) therapy pulse generators were investigated for their stability under radiation and their ability to change the absorbed dose from incident radiation. X-ray beams of 6 MV and 18 MV were used to quantify these results up to clinical doses of 68-78 Gy delivered in a single fraction. In the first part, the effect on electronic stimulation signaling of each pulse generator was monitored during and immediately afterwards with computer interrogation. In the second part, the effects of having the pulse generators scatter or attenuate the x-ray beam was also characterized from dose calculations on a treatment planning system as well as from actual radiation measurements. Some device models were found to be susceptible to radiation interference when placed directly in the beam of high energy therapeutic x-ray radiation. While some models exhibited no effect at all, others showed an apparent loss of stimulation output immediately after radiation was experienced. Still, other models were observed to have a cumulative dose effect with a reduced output signal, followed by battery depletion above 49 Gy. Absorbed dose changes on computer underestimated attenuation by nearly half for both energies amongst all pulse generators, although the computer did depict the proper shape of the changed distribution of dose around the device. Measured attenuation ranged from 7.0% to 11.0% at 6 MV and 4.2% to 5.2% at 18 MV for x-rays. Processes of back-scatter and side-scatter were deemed negligible although recorded. Identical results from 6 MV and 18 MV x-ray beams conclude no neutron effect was induced for the 18 MV beam. As there were documented effects identified in this research regarding pulse generation, it emphasizes the importance of caution when considering radiation therapy on patients with implanted VNS devices with observed malfunctions consequential. PMID:23032351

  4. Vagus nerve stimulator stability and interference on radiation oncology x-ray beams

    NASA Astrophysics Data System (ADS)

    Gossman, Michael S.; Ketkar, Amruta; Liu, Arthur K.; Olin, Bryan

    2012-10-01

    Five different models of Cyberonics, Inc. vagus nerve stimulation (VNS) therapy pulse generators were investigated for their stability under radiation and their ability to change the absorbed dose from incident radiation. X-ray beams of 6 MV and 18 MV were used to quantify these results up to clinical doses of 68-78 Gy delivered in a single fraction. In the first part, the effect on electronic stimulation signaling of each pulse generator was monitored during and immediately afterwards with computer interrogation. In the second part, the effects of having the pulse generators scatter or attenuate the x-ray beam was also characterized from dose calculations on a treatment planning system as well as from actual radiation measurements. Some device models were found to be susceptible to radiation interference when placed directly in the beam of high energy therapeutic x-ray radiation. While some models exhibited no effect at all, others showed an apparent loss of stimulation output immediately after radiation was experienced. Still, other models were observed to have a cumulative dose effect with a reduced output signal, followed by battery depletion above 49 Gy. Absorbed dose changes on computer underestimated attenuation by nearly half for both energies amongst all pulse generators, although the computer did depict the proper shape of the changed distribution of dose around the device. Measured attenuation ranged from 7.0% to 11.0% at 6 MV and 4.2% to 5.2% at 18 MV for x-rays. Processes of back-scatter and side-scatter were deemed negligible although recorded. Identical results from 6 MV and 18 MV x-ray beams conclude no neutron effect was induced for the 18 MV beam. As there were documented effects identified in this research regarding pulse generation, it emphasizes the importance of caution when considering radiation therapy on patients with implanted VNS devices with observed malfunctions consequential.

  5. Muscarinic contribution to the acute cortical effects of vagus nerve stimulation

    NASA Astrophysics Data System (ADS)

    Nichols, Justin A.

    2011-12-01

    Electrical stimulation of the vagus nerve (VNS) has been used to treat more than 60,000 patients with drug-resistant epilepsy and is under investigation as a treatment for several other neurological disorders and conditions. Among these, VNS increases memory performance and enhances recovery of motor and cognitive function in animal models of traumatic brain injury. Recent research indicates that pairing brief VNS with tones multiple-times a day for several weeks induces long-term, input specific cortical plasticity, which can be used to re-normalize the pathological cortical reorganization and eliminate a behavioral correlate of chronic tinnitus in noise exposed rats. Despite the therapeutic potential, the mechanisms of action of VNS remain speculative. In chapter 2 of this dissertation, the acute effects of VNS on cortical synchrony, excitability, and temporal processing are examined. In anesthetized rats implanted with multi-electrode arrays, VNS increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6 to 8 Hz, but not after systemic administration of the muscarinic antagonist scopolamine. Chapter 3 focuses on VNS-tone pairing induced cortical plasticity. Pairing VNS with a tone one hundred times in anesthetized rats resulted in frequency specific plasticity in 31% of the auditory cortex sites. Half of these sites exhibited a frequency specific increase in firing rate and half exhibited a frequency specific decrease. Muscarinic receptor blockade with scopolamine almost entirely prevented the frequency specific increases, but not decreases. Collectively, these experiments demonstrate the capacity for VNS to not only acutely influence cortical synchrony, and excitability, but to also influence temporal and spectral tuning via muscarinic receptor activation. These results strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in the mechanisms of action of VNS and

  6. Complications and safety of vagus nerve stimulation: 25 years of experience at a single center.

    PubMed

    Révész, David; Rydenhag, Bertil; Ben-Menachem, Elinor

    2016-07-01

    OBJECTIVE The goal of this paper was to investigate surgical and hardware complications in a longitudinal retrospective study. METHODS The authors of this registry study analyzed the surgical and hardware complications in 247 patients who underwent the implantation of a vagus nerve stimulation (VNS) device between 1990 and 2014. The mean follow-up time was 12 years. RESULTS In total, 497 procedures were performed for 247 primary VNS implantations. Complications related to surgery occurred in 8.6% of all implantation procedures that were performed. The respective rate for hardware complications was 3.7%. Surgical complications included postoperative hematoma in 1.9%, infection in 2.6%, vocal cord palsy in 1.4%, lower facial weakness in 0.2%, pain and sensory-related complications in 1.4%, aseptic reaction in 0.2%, cable discomfort in 0.2%, surgical cable break in 0.2%, oversized stimulator pocket in 0.2%, and battery displacement in 0.2% of patients. Hardware-related complications included lead fracture/malfunction in 3.0%, spontaneous VNS turn-on in 0.2%, and lead disconnection in 0.2% of patients. CONCLUSIONS VNS implantation is a relatively safe procedure, but it still involves certain risks. The most common complications are postoperative hematoma, infection, and vocal cord palsy. Although their occurrence rates are rather low at about 2%, these complications may cause major suffering and even be life threatening. To reduce complications, it is important to have a long-term perspective. The 25 years of follow-up of this study is of great strength considering that VNS can be a life-long treatment for many patients. Thus, it is important to include repeated surgeries such as battery and lead replacements, given that complications also may occur with these surgeries. PMID:27015521

  7. The central localization of the vagus nerve in the ferret (Mustela putorius furo) and the mink (Mustela vison).

    PubMed

    Ranson, R N; Butler, P J; Taylor, E W

    1993-05-01

    The location of vagal preganglionic neurones (VPN) has been determined in nine ferrets (Mustela putorius furo) and seven mink (M. vison) using neuronal tract-tracing techniques employing horseradish peroxidase (HRP) and wheat-germ agglutinin conjugated HRP (WGA-HRP) mixtures injected into the nodose ganglion of the vagus nerve. Labelled VPN were located ipsilaterally in the dorsal motor nucleus of the vagus (DmnX), nucleus ambiguus (nA), and reticular formation (rf) of the medulla oblongata. In four of the ferrets, labelled VPN were also identified in the nucleus dorsomedialis (ndm) and the nucleus of the spinal accessory nerve (nspa). In a single mink a few labelled cells were observed in the ndm but no labelled VPN were found in the nspa. Labelling of afferent components of the vagus nerve was seen in two ferrets and two mink with the best labelling obtained following an injection of an HRP/WGA-HRP mixture into the nodose ganglion. Labelled afferents were observed to cross the ipsilateral spinal trigeminal tract (SpV) before entering the tractus solitarius (TS) in regions separate from the motor axons which exit the medulla in separate fasicles. Sensory terminal fields were identified bilaterally in the nucleus of the tractus solitarius (nTS) in both species and bilaterally in the area postrema (ap) of the ferret; however, the contralateral labelling was sparse in comparison to the densely labelled ipsilateral nTS/ap. Maximal terminal labelling was seen in regions just rostral and caudal to obex in both species. PMID:7686926

  8. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes

    PubMed Central

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-sang J.; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Guyenet, Patrice G.

    2016-01-01

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes. PMID:27088805

  9. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.

    PubMed

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-Sang J; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Rosin, Diane L; Guyenet, Patrice G; Okusa, Mark D

    2016-05-01

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes. PMID:27088805

  10. Vagus nerve stimulation: state of the art of stimulation and recording strategies to address autonomic function neuromodulation

    NASA Astrophysics Data System (ADS)

    Guiraud, David; Andreu, David; Bonnet, Stéphane; Carrault, Guy; Couderc, Pascal; Hagège, Albert; Henry, Christine; Hernandez, Alfredo; Karam, Nicole; Le Rolle, Virginie; Mabo, Philippe; Maciejasz, Paweł; Malbert, Charles-Henri; Marijon, Eloi; Maubert, Sandrine; Picq, Chloé; Rossel, Olivier; Bonnet, Jean-Luc

    2016-08-01

    Objective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans.

  11. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    PubMed

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

  12. [The Importance of Vagus Nerve Afferent in the Formation of Emotions in Attention-Deficit Hyperactivity Disorder Model Rat].

    PubMed

    Hida, Hideki

    2016-06-01

    It is of interest to know how environmental stimuli contribute to the formation of emotion during development. In a rat model of attention-deficit hyperactivity disorder, monosodium L- glutamate (MSG), a taste substance of umami, was administered for 5 weeks during developmental period, followed by emotional behavior tests such as open-field test and social interaction test in adulthood. Although no significant change was observed in anxiety-like behavior, MSG intake caused a reduction in aggressive behavior. Vagotomy under the level of diaphragm resulted in eliminating the MSG effect on aggression, indicating the importance of neuronal activity of the vagus nerve in this effect. Futher studies will focus on futher questions regarding the gut-brain axis such as the change of microbiota and the mechanism of the axis in the brain. PMID:27279161

  13. Early Parasympathetic Reinnervation Is Not Related to Reconnection of Major Branches of the Vagus Nerve after Heart Transplantation

    PubMed Central

    Lee, So-Ryoung; Kang, Do-Yoon; Cho, Youngjin; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Eue-Keun

    2016-01-01

    Background and Objectives Bicaval heart transplantation (HTx) may promote parasympathetic reinnervation. However, the prevalence and timing of reinnervation have not been fully investigated. Heart rate variability (HRV) and direct vagal stimulation were used to evaluate the presence of parasympathetic reinnervation after bicaval HTx. Subjects and Methods A total of 21 patients (time after HTx 0.52-4.41 years, mean 1.8±1.2 years) who received a bicaval HTx was enrolled. Reinnervation was evaluated using HRV values from 24-hour Holter recordings. A cross-sectional analysis of the HRV at 0.5-1, 1-2, and >2 years after HTx was performed. We also applied high-frequency electrical stimulation (16.7 Hz, 1 msec pulse width, ≤10 V) to the cardiac branches of the vagus nerve at the level of the superior vena cava in eight patients at 6 and 12 months after HTx. Results The degree of parasympathetic reinnervation corresponded to the time after HTx. The HRV analysis revealed that the root mean square of the successive differences between consecutive RR-intervals (RMSSD) and high-frequency power were significantly higher during the late period (>2 years) compared with the early period (0.5-1 year) after HTx. None of the eight patients who underwent direct vagal stimulation responded during the stimulation at 6 and 12 months, whereas incremental trends in HRV parameters were observed, which indicated that parasympathetic reinnervation began within 1 year after HTx. Conclusion Parasympathetic reinnervation seemed to begin in the early period (<1 year) after bicaval HTx. Reconnection of major branches of the vagus nerve may not be related to early reinnervation. PMID:27014350

  14. Effects of vagus nerve stimulation via cholinergic anti-inflammatory pathway activation on myocardial ischemia/reperfusion injury in canine

    PubMed Central

    Zhang, Rong; Wugeti, Najina; Sun, Juan; Yan, Huang; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi; Liu, Haili; Ma, Yitong

    2014-01-01

    Background: Acute myocardial infarction (AMI) was a type of disease with high mortality rate and high disability rate. And about 50% of the final area of myocardial infarction after AMI was led by ischemia/reperfusion (I/R) injury. The I/R injury was a kind of systemic inflammatory response, in which the main performance laid in the release of the large quantity of inflammatory cytokines. The basic experiments, clinical studies and the large scaled epidemiology investigations found that the low functions of vagus nerves had close relevance with the occurrence, development and prognosis of the cardiovascular diseases. This study investigate the effects of cholinergic anti-inflammatory pathway with with vagus never stimulation I/R injury in canine. Methods: 18 adult mongrel dogs were randomly divided into 3 groups (n = 6): sham operation group (sham Group), ischemia/reperfusion group (I/R group), right vagus nerve stimulation and ischemia/reperfusion group (STM group). The hemodynamic indexes were measured after reperfusion 120 min. Through internal jugular venous blood, serum acetylcholine (Ach), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) concentrations were detected by ELISA. Alpha 7 subunit Ach acetylcholine receptor (α7nAchR) expression level was detected with immunohistochemical method. HE staining was used to observe the degree of neutrophil infiltration. Results: After ischemia/reperfusion 120 min, compared with sham group, TNF-α and IL-6 were significantly decreased, Ach content increased, the expression of α7nAchR protein was significantly reduced in I/R group (P < 0.05). Expression of α7nAchR protein, Ach content, TNF-α and IL-6 level had no significant difference in STM group (P < 0.05). Compared with I/R group, the expression of Ach and α7nAchR protein significantly increased the TNF- and IL-6 levels decreased in STM group (P < 0.05). Compared with the baseline, TNF-α and IL-6 levels significantly increased Ach content decreased

  15. Effects of sympathetic stimulation and applied catecholamines on mechanical and electrical responses to stimulation of the vagus nerve in guinea-pig isolated trachea.

    PubMed Central

    McCaig, D. J.

    1987-01-01

    Mechanical and electrical responses to stimulation of the vagus nerve were studied in the isolated, innervated trachea of the guinea-pig. In approximately half the preparations tested, the amplitudes of mechanical constrictor responses to stimulation of the vagus were reduced substantially during a period of sympathetic stimulation. Vagal responses were unaltered in the remainder. In single trachealis cells, stimulation of the vagus nerve or sympathetic stellate ganglion elicited depolarization and hyperpolarization, respectively. Vagally-mediated depolarization was decreased, unchanged or increased in amplitude after a period of sympathetic stimulation. Isoprenaline almost abolished mechanical responses induced by stimulation of the vagus, and this effect was blocked by propranolol. Noradrenaline attenuated markedly vagal mechanical responses also, and this effect was blocked by a combination of propranolol and phentolamine. Both noradrenaline and isoprenaline hyperpolarized single trachealis cells and greatly reduced the amplitude of vagally-mediated depolarization. Neither sympathetic stimulation nor applied catecholamines altered mechanical responses to applied acetylcholine, strongly suggesting that their effects on vagal responses are predominantly presynaptic. PMID:3607363

  16. Effect of copper sulphate on the rate of afferent discharge in the gastric branch of the vagus nerve in the rat

    NASA Technical Reports Server (NTRS)

    Niijima, Akira; Jiang, Zheng-Yao; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The afferent nerve activity was recorded from a nerve filament isolated from the peripheral cut end of the gastric branch of the vagus nerve. The gastric perfusion of 4 ml of two different concentrations (0.04 percent and 0.08 percent) of CuSO4 solution provoked an increase in afferent activity. The stimulating effect of the 0.08 percent solution was stronger than that of the 0.04 percent solution, and lasted for a longer period of time. The observations suggest a possible mechanism by which CuSO4 elicits emesis.

  17. Intraoperative radiation of canine carotid artery, internal jugular vein, and vagus nerve. Therapeutic applications in the management of advanced head and neck cancers

    SciTech Connect

    Mittal, B.B.; Pelzer, H.; Tsao, C.S.; Ward, W.F.; Johnson, P.; Friedman, C.; Sisson, G.A. Sr.; Kies, M. )

    1990-12-01

    As a step in the application of intraoperative radiotherapy (IORT) for treating advanced head and neck cancers, preliminary information was obtained on the radiation tolerance of the canine common carotid artery, internal jugular vein, and vagus nerve to a single, high-dose electron beam. Both sides of the neck of eight mongrel dogs were operated on to expose an 8-cm segment of common carotid artery, internal jugular vein, and vagus nerve. One side of the neck was irradiated, using escalating doses of 2500, 3500, 4500, and 5500 cGy. The contralateral side of the neck served as the unirradiated control. At 3 and 6 months after IORT, one dog at each dose level was killed. None of the dogs developed carotid bleeding at any time after IORT. Light microscopic investigations using hematoxylin-eosin staining on the common carotid artery and internal jugular vein showed no consistent changes that suggested radiation damage; however, the Masson trichrome stain and hydroxyproline concentration of irradiated common carotid artery indicated an increase in the collagen content of the tunica media. Marked changes in the irradiated vagus nerve were seen, indicating severe demyelination and loss of nerve fibers, which appeared to be radiation-dose dependent. Four patients with advanced recurrent head and neck cancer were treated with surgical resection and IORT without any acute or subacute complications. The role of IORT as a supplement to surgery, external beam irradiation, and chemotherapy in selected patients with advanced head and neck cancer needs further exploration.

  18. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig.

    PubMed

    Beaumont, Eric; Wright, Gary L; Southerland, Elizabeth M; Li, Ying; Chui, Ray; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2016-05-15

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15-20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  19. Novel insights into maladaptive behaviours in Prader–Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation

    PubMed Central

    McAllister, C. J.; Ring, H. A.; Finer, N.; Kelly, C. L.; Sylvester, K. P.; Fletcher, P. C.; Morrell, N. W.; Garnett, M. R.; Manford, M. R. A.; Holland, A. J.

    2015-01-01

    Abstract Background We report striking and unanticipated improvements in maladaptive behaviours in Prader–Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild–moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. Methods Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post‐implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. Results Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food‐seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. Conclusions We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally. PMID:26018613

  20. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

    PubMed Central

    George, Mark S; Aston-Jones, Gary

    2010-01-01

    Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies. PMID:19693003

  1. Modulation of Muscle Tone and Sympathovagal Balance in Cervical Dystonia Using Percutaneous Stimulation of the Auricular Vagus Nerve.

    PubMed

    Kampusch, Stefan; Kaniusas, Eugenijus; Széles, Jozsef C

    2015-10-01

    Primary cervical dystonia is characterized by abnormal, involuntary, and sustained contractions of cervical muscles. Current ways of treatment focus on alleviating symptomatic muscle activity. Besides pharmacological treatment, in severe cases patients may receive neuromodulative intervention such as deep brain stimulation. However, these (highly invasive) methods have some major drawbacks. For the first time, percutaneous auricular vagus nerve stimulation (pVNS) was applied in a single case of primary cervical dystonia. Auricular vagus nerve stimulation was already shown to modulate the (autonomous) sympathovagal balance of the body and proved to be an effective treatment in acute and chronic pain, epilepsy, as well as major depression. pVNS effects on cervical dystonia may be hypothesized to rely upon: (i) the alteration of sensory input to the brain, which affects structures involved in the genesis of motoric and nonmotoric dystonic symptoms; and (ii) the alteration of the sympathovagal balance with a sustained impact on involuntary movement control, pain, quality of sleep, and general well-being. The presented data provide experimental evidence that pVNS may be a new alternative and minimally invasive treatment in primary cervical dystonia. One female patient (age 50 years) suffering from therapy refractory cervical dystonia was treated with pVNS over 20 months. Significant improvement in muscle pain, dystonic symptoms, and autonomic regulation as well as a subjective improvement in motility, sleep, and mood were achieved. A subjective improvement in pain recorded by visual analog scale ratings (0-10) was observed from 5.42 to 3.92 (medians). Muscle tone of the mainly affected left and right trapezius muscle in supine position was favorably reduced by about 96%. Significant reduction of muscle tone was also achieved in sitting and standing positions of the patient. Habituation to stimulation leading to reduced stimulation efficiency was observed and

  2. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve.

    PubMed

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  3. Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve

    PubMed Central

    Honig, Gerard; Mader, Simone; Chen, Huiyi; Porat, Amit; Ochani, Mahendar; Wang, Ping; Volpe, Bruce T.; Diamond, Betty

    2016-01-01

    Systemic infection can initiate or exacerbate central nervous system (CNS) pathology, even in the absence of overt invasion of bacteria into the CNS. Recent epidemiological studies have demonstrated that human survivors of sepsis have an increased risk of long-term neurocognitive decline. There is thus a need for improved understanding of the physiological mechanisms whereby acute sepsis affects the CNS. In particular, MyD88-dependent activation of brain microvascular endothelial cells and a resulting loss of blood-brain barrier integrity have been proposed to play an important role in the effects of systemic inflammation on the CNS. Signaling through the vagus nerve has also been considered to be an important component of CNS responses to systemic infection. Here, we demonstrate that blood-brain barrier permeabilization and hippocampal transcriptional responses during polymicrobial sepsis occur even in the absence of MyD88-dependent signaling in cerebrovascular endothelial cells. We further demonstrate that these transcriptional responses can occur without vagus nerve input. These results suggest that redundant signals mediate CNS responses in sepsis. Either endothelial or vagus nerve activation may be individually sufficient to transmit systemic inflammation to the central nervous system. Transcriptional activation in the forebrain in sepsis may be mediated by MyD88-independent endothelial mechanisms or by non-vagal neuronal pathways. PMID:26790027

  4. Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle.

    PubMed

    Larsen, Lars E; Wadman, Wytse J; Marinazzo, Daniele; van Mierlo, Pieter; Delbeke, Jean; Daelemans, Sofie; Sprengers, Mathieu; Thyrion, Lisa; Van Lysebettens, Wouter; Carrette, Evelien; Boon, Paul; Vonck, Kristl; Raedt, Robrecht

    2016-07-01

    Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7 s on, 18 s off) and standard cycle (30 s on, 300 s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8 Hz) and high gamma (75-150 Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300 μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy. PMID:27102987

  5. Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study.

    PubMed

    Hasan, Alkomiet; Wolff-Menzler, Claus; Pfeiffer, Sebastian; Falkai, Peter; Weidinger, Elif; Jobst, Andrea; Hoell, Imke; Malchow, Berend; Yeganeh-Doost, Peyman; Strube, Wolfgang; Quast, Silke; Müller, Norbert; Wobrock, Thomas

    2015-10-01

    Despite many pharmacological and psychosocial treatment options, schizophrenia remains a debilitating disorder. Thus, new treatment strategies rooted in the pathophysiology of the disorder are needed. Recently, vagus nerve stimulation (VNS) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia. The objective of this study was to investigate for the first time the feasibility, safety and efficacy of transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham-controlled, double-blind trial was conducted from 2010 to 2012. Twenty schizophrenia patients were randomly assigned to one of two treatment groups. The first group (active tVNS) received daily active stimulation of the left auricle for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation. Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12. Various other secondary measures were assessed to investigate safety and efficacy. The intervention was well tolerated with no relevant adverse effects. We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period. Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups. Application of tVNS was well tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia, the overall pattern of symptom change might warrant further investigations in this population. PMID:26210303

  6. Vagus Nerve Stimulation Exerts the Neuroprotective Effects in Obese-Insulin Resistant Rats, Leading to the Improvement of Cognitive Function

    PubMed Central

    Chunchai, Titikorn; Samniang, Bencharunan; Sripetchwandee, Jirapas; Pintana, Hiranya; Pongkan, Wanpitak; Kumfu, Sirinart; Shinlapawittayatorn, Krekwit; KenKnight, Bruce H; Chattipakorn, Nipon; Chattipakorn, Siriporn C.

    2016-01-01

    Vagus nerve stimulation (VNS) therapy was shown to improve peripheral insulin sensitivity. However, the effects of chronic VNS therapy on brain insulin sensitivity, dendritic spine density, brain mitochondrial function, apoptosis and cognition in obese-insulin resistant subjects have never been investigated. Male Wistar rats (n = 24) were fed with either a normal diet (n = 8) or a HFD (n = 16) for 12 weeks. At week 13, HFD-fed rats were divided into 2 groups (n = 8/group). Each group was received either sham therapy or VNS therapy for an additional 12 weeks. At the end of treatment, cognitive function, metabolic parameters, brain insulin sensitivity, brain mitochondrial function, brain apoptosis, and dendritic spines were determined in each rat. The HFD-fed with Sham therapy developed brain insulin resistance, brain oxidative stress, brain inflammation, and brain apoptosis, resulting in the cognitive decline. The VNS group showed an improvement in peripheral and brain insulin sensitivity. VNS treatment attenuated brain mitochondrial dysfunction and cell apoptosis. In addition, VNS therapy increased dendritic spine density and improved cognitive function. These findings suggest that VNS attenuates cognitive decline in obese-insulin resistant rats by attenuating brain mitochondrial dysfunction, improving brain insulin sensitivity, decreasing cell apoptosis, and increasing dendritic spine density. PMID:27226157

  7. The timing and amount of vagus nerve stimulation during rehabilitative training affect post-stroke recovery of forelimb strength

    PubMed Central

    Hays, Seth A.; Khodaparast, Navid; Ruiz, Andrea; Sloan, Andrew M.; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

    2014-01-01

    Loss of upper arm strength after stroke is a leading cause of disability. Strategies that can enhance the benefits of rehabilitative training could improve motor function after stroke. Recent studies in a rat model of ischemic stroke demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training substantially improves recovery of forelimb strength compared to extensive rehabilitative training without VNS. Here we report that the timing and amount of stimulation affect the degree of forelimb strength recovery. Similar amounts of delayed VNS delivered two hours after daily rehabilitative training sessions resulted in significantly less improvement compared to VNS that is paired with identical rehabilitative training. Significantly less recovery also occurred when several-fold more VNS was delivered during rehabilitative training. Both delayed and additional VNS confer moderately improved recovery compared to extensive rehabilitative training without VNS, but fail to enhance recovery to the same degree as VNS that is timed to occur with successful movements. These findings confirm that VNS paired with rehabilitative training holds promise for restoring forelimb strength post-stroke and indicate that both the timing and amount of VNS should be optimized to maximize therapeutic benefits. PMID:24818637

  8. Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats.

    PubMed

    Hays, Seth A; Ruiz, Andrea; Bethea, Thelma; Khodaparast, Navid; Carmel, Jason B; Rennaker, Robert L; Kilgard, Michael P

    2016-07-01

    Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% ± 19% recovery, whereas VNS paired with rehabilitative training yields a 98% ± 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID:27255820

  9. Adjunctive vagus nerve stimulation for treatment-resistant bipolar disorder: managing device failure or the end of battery life.

    PubMed

    Pardo, José V

    2016-01-01

    The vagus nerve stimulation (VNS) device is used not only to treat refractory seizure disorders but also mood disorders; the latter indication received CE Mark approval in 2001 and Food and Drug Administration approval in 2005. Original estimates for the end of battery life (EOBL) were approximately 6-10 years. Many neuropsychiatric patients have or will soon face EOBL. A patient with severe, life-threatening, treatment-resistant bipolar disorder underwent 9 years of stable remission following 20 months of adjunctive VNS. The device ceased operation at EOBL. Because of logistical issues, re-initiation of VNS was delayed over several months. The patient relapsed with depression, mania and mixed states, and regained remission 17 months after device replacement. This case dictates prudence in managing stable patients in remission with VNS. If the device malfunctions, urgent surgical replacement is warranted with subsequent rapid titration to previous parameters as tolerated. Several months' delay may trigger relapse and prove difficult to re-establish remission. PMID:26951440

  10. Vagus Nerve Stimulation Exerts the Neuroprotective Effects in Obese-Insulin Resistant Rats, Leading to the Improvement of Cognitive Function.

    PubMed

    Chunchai, Titikorn; Samniang, Bencharunan; Sripetchwandee, Jirapas; Pintana, Hiranya; Pongkan, Wanpitak; Kumfu, Sirinart; Shinlapawittayatorn, Krekwit; KenKnight, Bruce H; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2016-01-01

    Vagus nerve stimulation (VNS) therapy was shown to improve peripheral insulin sensitivity. However, the effects of chronic VNS therapy on brain insulin sensitivity, dendritic spine density, brain mitochondrial function, apoptosis and cognition in obese-insulin resistant subjects have never been investigated. Male Wistar rats (n = 24) were fed with either a normal diet (n = 8) or a HFD (n = 16) for 12 weeks. At week 13, HFD-fed rats were divided into 2 groups (n = 8/group). Each group was received either sham therapy or VNS therapy for an additional 12 weeks. At the end of treatment, cognitive function, metabolic parameters, brain insulin sensitivity, brain mitochondrial function, brain apoptosis, and dendritic spines were determined in each rat. The HFD-fed with Sham therapy developed brain insulin resistance, brain oxidative stress, brain inflammation, and brain apoptosis, resulting in the cognitive decline. The VNS group showed an improvement in peripheral and brain insulin sensitivity. VNS treatment attenuated brain mitochondrial dysfunction and cell apoptosis. In addition, VNS therapy increased dendritic spine density and improved cognitive function. These findings suggest that VNS attenuates cognitive decline in obese-insulin resistant rats by attenuating brain mitochondrial dysfunction, improving brain insulin sensitivity, decreasing cell apoptosis, and increasing dendritic spine density. PMID:27226157

  11. Localization of Interictal Epileptiform Activity Using Magnetoencephalography with Synthetic Aperture Magnetometry in Patients with a Vagus Nerve Stimulator

    PubMed Central

    Stapleton-Kotloski, Jennifer R.; Kotloski, Robert J.; Boggs, Jane A.; Popli, Gautam; O’Donovan, Cormac A.; Couture, Daniel E.; Cornell, Cassandra; Godwin, Dwayne W.

    2014-01-01

    Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS. We used synthetic aperture magnetometry (g2) [SAM(g2)], an adaptive beamformer that maps the excessive kurtosis, to map interictal spikes to the coregistered MRI image, despite the presence of contaminating VNS artifact. We present a series of eight patients with a VNS who underwent MEG recording. Localization of interictal epileptiform activity by SAM(g2) is compared to invasive electrophysiologic monitoring and other localizing approaches. While the raw MEG recordings were uninterpretable, analysis of the recordings with SAM(g2) identified foci of peak kurtosis and source signal activity that was unaffected by the VNS artifact. SAM(g2) analysis of MEG recordings in patients with a VNS produces interpretable results and expands the use of MEG for the pre-surgical evaluation of epilepsy. PMID:25505894

  12. Feasibility and Safety of Transcutaneous Vagus Nerve Stimulation Paired with Notched Music Therapy for the Treatment of Chronic Tinnitus

    PubMed Central

    Kwak, Min Young; An, Yong-Hwi; Kim, Dong Hyun; Kim, Yun Jin; Kim, Hyo Jung

    2015-01-01

    Background and Objectives A recent study demonstrated that tinnitus could be eliminated by vagus nerve stimulation (VNS) paired with notched sounds in a rat tinnitus model. The aims of this clinical study were to investigate the effects and safety of transcutaneous VNS (tVNS) by patch-type electrode paired with notched music for treating chronic tinnitus. Subjects and Methods Thirty patients with refractory chronic tinnitus for >12 months were included in this study. A patch-type electrode was attached to the auricular concha of the patient's left ear and tVNS was performed for 30 min (pulse rate 25 Hz, pulse width 200 µs, and amplitude 1-10 mA) using a transcutaneous electric nerve stimulation eco2. During tVNS, the patients listened to notched music cleared of the frequency spectrum corresponding to the tinnitus with a 0.5 octave notch width. Results After 10 treatment sessions, 15/30 patients (50%) reported symptom relief in terms of a global improvement questionnaire. The mean tinnitus loudness (10-point scale) and the mean tinnitus awareness score (%) improved significantly from 6.32±2.06 to 5.16±1.52 and from 82.40±24.37% to 65.60±28.15%, respectively (both p<0.05). None of the patients had any specific side effects, such as changes in heart rate or blood pressure. Conclusions This study has demonstrated the feasibility and safety of tVNS paired with notched music therapy in patients with chronic tinnitus, with the use of a pad-type electrode attached to the auricular concha. PMID:26771015

  13. Brain activation during vaginocervical self-stimulation and orgasm in women with complete spinal cord injury: fMRI evidence of mediation by the vagus nerves.

    PubMed

    Komisaruk, Barry R; Whipple, Beverly; Crawford, Audrita; Liu, Wen-Ching; Kalnin, Andrew; Mosier, Kristine

    2004-10-22

    Women diagnosed with complete spinal cord injury (SCI) at T10 or above report vaginal-cervical perceptual awareness. To test whether the Vagus nerves, which bypass the spinal cord, provide the afferent pathway for this response, we hypothesized that the Nucleus Tractus Solitarii (NTS) region of the medulla oblongata, to which the Vagus nerves project, is activated by vaginal-cervical self-stimulation (CSS) in such women, as visualized by functional magnetic resonance imaging (fMRI). Regional blood oxygen level-dependent (BOLD) signal intensity was imaged during CSS and other motor and sensory procedures, using statistical parametric mapping (SPM) analysis with head motion artifact correction. Physiatric examination and MRI established the location and extent of spinal cord injury. In order to demarcate the NTS, a gustatory stimulus and hand movement were used to activate the superior region of the NTS and the Nucleus Cuneatus adjacent to the inferior region of the NTS, respectively. Each of four women with interruption, or "complete" injury, of the spinal cord (ASIA criteria), and one woman with significant, but "incomplete" SCI, all at or above T10, showed activation of the inferior region of the NTS during CSS. Each woman showed analgesia, measured at the fingers, during CSS, confirming previous findings. Three women experienced orgasm during the CSS. The brain regions that showed activation during the orgasms included hypothalamic paraventricular nucleus, medial amygdala, anterior cingulate, frontal, parietal, and insular cortices, and cerebellum. We conclude that the Vagus nerves provide a spinal cord-bypass pathway for vaginal-cervical sensibility in women with complete spinal cord injury above the level of entry into spinal cord of the known genitospinal nerves. PMID:15451368

  14. Transcompartmental reversal of single fibre hyperexcitability in juxtaparanodal Kv1.1-deficient vagus nerve axons by activation of nodal KCNQ channels.

    PubMed

    Glasscock, Edward; Qian, Jing; Kole, Matthew J; Noebels, Jeffrey L

    2012-08-15

    Kv1.1 channels cluster at juxtaparanodes of myelinated axons in the vagus nerve, the primary conduit for parasympathetic innervation of the heart. Kcna1-null mice lacking these channels exhibit neurocardiac dysfunction manifested by atropine-sensitive atrioventricular conduction blocks and bradycardia that may culminate in sudden death. To evaluate whether loss of Kv1.1 channels alters electrogenic properties within the nerve, we compared the intrinsic excitability of single myelinated A- and Aδ-axons from excised cervical vagus nerves of young adult Kcna1-null mice and age-matched, wild-type littermate controls. Although action potential shapes and relative refractory periods varied little between genotypes, Kv1.1-deficient large myelinated A-axons showed a fivefold increase in susceptibility to 4-aminopyridine (4-AP)-induced spontaneous ectopic firing. Since the repolarizing currents of juxtaparanodal Kv1 channels and nodal KCNQ potassium channels both act to dampen repetitive activity, we examined whether augmenting nodal KCNQ activation could compensate for Kv1.1 loss and reverse the spontaneous hyperexcitability in Kv1.1-deficient A-axons. Application of the selective KCNQ opener flupirtine raised A-axon firing threshold while profoundly suppressing 4-AP-induced spontaneous firing, demonstrating a functional synergy between the two compartments. We conclude that juxtaparanodal Kv1.1-deficiency causes intrinsic hyperexcitability in large myelinated axons in vagus nerve which could contribute to autonomic dysfunction in Kcna1-null mice, and that KCNQ openers reveal a transcompartmental synergy between Kv1 and KCNQ channels in regulating axonal excitability. PMID:22641786

  15. Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use.

    PubMed

    Terra, Vera C; Amorim, Ricardo; Silvado, Carlos; Oliveira, Andrea Julião de; Jorge, Carmen Lisa; Faveret, Eduardo; Ragazzo, Paulo; De Paola, Luciano

    2013-11-01

    Epilepsy comprises a set of neurologic and systemic disorders characterized by recurrent spontaneous seizures, and is the most frequent chronic neurologic disorder. In patients with medically refractory epilepsy, therapeutic options are limited to ablative brain surgery, trials of experimental antiepileptic drugs, or palliative surgery. Vagal nerve stimulation is an available palliative procedure of which the mechanism of action is not understood, but with established efficacy for medically refractory epilepsy and low incidence of side-effects. In this paper we discuss the recommendations for VNS use as suggested by the Brazilian League of Epilepsy and the Scientific Department of Epilepsy of the Brazilian Academy of Neurology Committee of Neuromodulation. PMID:24394879

  16. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke

    PubMed Central

    Pierce, David; Dixit, Anand; Kimberley, Teresa J.; Robertson, Michele; Tarver, Brent; Hilmi, Omar; McLean, John; Forbes, Kirsten; Kilgard, Michael P.; Rennaker, Robert L.; Cramer, Steven C.; Walters, Matthew; Engineer, Navzer

    2016-01-01

    Background and Purpose— Recent animal studies demonstrate that vagus nerve stimulation (VNS) paired with movement induces movement-specific plasticity in motor cortex and improves forelimb function after stroke. We conducted a randomized controlled clinical pilot study of VNS paired with rehabilitation on upper-limb function after ischemic stroke. Methods— Twenty-one participants with ischemic stroke >6 months before and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three 2-hour sessions per week for 6 weeks, each involving >400 movement trials. In the VNS group, movements were paired with 0.5-second VNS. The primary objective was to assess safety and feasibility. Secondary end points included change in upper-limb measures (including the Fugl–Meyer Assessment-Upper Extremity). Results— Nine participants were randomized to VNS plus rehabilitation and 11 to rehabilitation alone. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five had minor adverse device effects including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl–Meyer Assessment-Upper Extremity scores was not significantly different (between-group difference, 5.7 points; 95% confidence interval, −0.4 to 11.8). In the per-protocol analysis, there was a significant difference in change in Fugl–Meyer Assessment-Upper Extremity score (between-group difference, 6.5 points; 95% confidence interval, 0.4 to 12.6). Conclusions— This study suggests that VNS paired with rehabilitation is feasible and has not raised safety concerns. Additional studies of VNS in adults with chronic stroke will now be performed. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01669161. PMID:26645257

  17. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression

    PubMed Central

    Conway, Charles R.; Chibnall, John T.; Gebara, Marie Anne; Price, Joseph L.; Snyder, Abraham Z.; Mintun, Mark A.; (Bud) Craig, A.D.; Cornell, Martha E.; Perantie, Dana C.; Giuffra, Luis A.; Bucholz, Richard D.; Sheline, Yvette I.

    2014-01-01

    Background Vagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD. Objective 17Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months. Methods Thirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders. Results A significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (Puncorrected = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders. Conclusions/Limitations VNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications. PMID:23485649

  18. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study

    PubMed Central

    Diener, Hans-Christoph; Silver, Nicholas; Magis, Delphine; Reuter, Uwe; Andersson, Annelie; Liebler, Eric J; Straube, Andreas

    2015-01-01

    Background Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH. Methods PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed. Results During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred. Conclusion Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC. PMID:26391457

  19. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

    PubMed

    Davey, P G; Charter, M; Kelly, S; Varma, T R; Jacobson, I; Freeman, A; Precious, E; Lambert, J

    1994-06-01

    Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken from all patients; a sample of cerebrospinal fluid (CSF) uncontaminated with blood was obtained from five patients. Serum and brain tissue samples were assayed by high-pressure liquid chromatography. Drug concentrations in brain tissue exceeded those in CSF by 1.8- to 19.4-fold. Kinetic modeling suggested that peak sparfloxacin concentrations in brain tissue may have occurred later than 3 to 5 h and that actual peak concentrations may therefore have been higher (up to 10 micrograms/g of tissue). The activities of ciprofloxacin and sparfloxacin as antagonists of the gamma-aminobutyric acid antagonist (GABAA) receptor were measured with the rat vagus nerve preparation. The 50% inhibitory concentration (IC50) of ciprofloxacin was 250 microM (95.25 micrograms/ml), but in the presence of biphenyl acetic acid (BPAA), the IC50 of ciprofloxacin was only 0.6 microM (0.23 microgram/ml). In contrast, the IC50 of sparfloxacin alone or in the presence of BPAA was > 300 microM (> 100 micrograms/ml). We conclude that the concentrations of ciprofloxacin and sparfloxacin in brain tissue may exceed serum drug concentrations and cannot be predicted from the concentrations in CSF. Sparfloxacin does not have any activity as a GABA antagonist, either alone or in the presence of BPAA, at the concentrations which are likely to be reached in human brain tissue. PMID:8092837

  20. Ciprofloxacin and sparfloxacin penetration into human brain tissue and their activity as antagonists of GABAA receptor of rat vagus nerve.

    PubMed Central

    Davey, P G; Charter, M; Kelly, S; Varma, T R; Jacobson, I; Freeman, A; Precious, E; Lambert, J

    1994-01-01

    Patients undergoing elective surgery for removal of brain tumors, aneurysms, or other vascular malformations were administered a single oral dose of sparfloxacin (400 mg; 16 patients) or ciprofloxacin (750 mg; 5 patients) either 3 to 5 h or 22 to 26 h before surgery. Serum samples were taken from all patients at 0, 1, 3 to 5, 7 to 9, and 22 to 26 h after dosing; an additional serum sample was obtained at 48 h from patients who received sparfloxacin. A single sample of brain tissue was taken from all patients; a sample of cerebrospinal fluid (CSF) uncontaminated with blood was obtained from five patients. Serum and brain tissue samples were assayed by high-pressure liquid chromatography. Drug concentrations in brain tissue exceeded those in CSF by 1.8- to 19.4-fold. Kinetic modeling suggested that peak sparfloxacin concentrations in brain tissue may have occurred later than 3 to 5 h and that actual peak concentrations may therefore have been higher (up to 10 micrograms/g of tissue). The activities of ciprofloxacin and sparfloxacin as antagonists of the gamma-aminobutyric acid antagonist (GABAA) receptor were measured with the rat vagus nerve preparation. The 50% inhibitory concentration (IC50) of ciprofloxacin was 250 microM (95.25 micrograms/ml), but in the presence of biphenyl acetic acid (BPAA), the IC50 of ciprofloxacin was only 0.6 microM (0.23 microgram/ml). In contrast, the IC50 of sparfloxacin alone or in the presence of BPAA was > 300 microM (> 100 micrograms/ml). We conclude that the concentrations of ciprofloxacin and sparfloxacin in brain tissue may exceed serum drug concentrations and cannot be predicted from the concentrations in CSF. Sparfloxacin does not have any activity as a GABA antagonist, either alone or in the presence of BPAA, at the concentrations which are likely to be reached in human brain tissue. PMID:8092837

  1. The Role of the Vagus Nerve in the Migrating Motor Complex and Ghrelin- and Motilin-Induced Gastric Contraction in Suncus

    PubMed Central

    Miyano, Yuki; Sakata, Ichiro; Kuroda, Kayuri; Aizawa, Sayaka; Tanaka, Toru; Jogahara, Takamichi; Kurotani, Reiko; Sakai, Takafumi

    2013-01-01

    The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious suncus—a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng·kg−1·min−1 for 10 min) during phase I had induced phase III–like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 µg·kg−1·min−1 for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng·kg−1·min−1 for 10 min) did not induce phase III–like contractions in sham-operated suncus. However, in vagotomized suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III–like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II of the MMC via the vagus nerve in suncus. Furthermore, the vagus nerve is essential for initiating postprandial contractions, and inhibition of the phase III–like contractions induced by motilin is highly dependent on the vagus nerve. PMID:23724093

  2. The role of the vagus nerve in the migrating motor complex and ghrelin- and motilin-induced gastric contraction in suncus.

    PubMed

    Miyano, Yuki; Sakata, Ichiro; Kuroda, Kayuri; Aizawa, Sayaka; Tanaka, Toru; Jogahara, Takamichi; Kurotani, Reiko; Sakai, Takafumi

    2013-01-01

    The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious suncus-a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) during phase I had induced phase III-like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 µg·kg(-1)·min(-1) for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) did not induce phase III-like contractions in sham-operated suncus. However, in vagotomized suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III-like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II of the MMC via the vagus nerve in suncus. Furthermore, the vagus nerve is essential for initiating postprandial contractions, and inhibition of the phase III-like contractions induced by motilin is highly dependent on the vagus nerve. PMID:23724093

  3. Vagus nerve stimulation…25 years later! What do we know about the effects on cognition?

    PubMed

    Vonck, Kristl; Raedt, Robrecht; Naulaerts, Joke; De Vogelaere, Frederick; Thiery, Evert; Van Roost, Dirk; Aldenkamp, Bert; Miatton, Marijke; Boon, Paul

    2014-09-01

    VNS therapy was delivered to patients for the first time in 1988. After 25 years, insight in the antiepileptic and antidepressant mechanism of action of VNS has grown steadily. The effects on cognition and especially memory remain controversial. This review provides an elaborate overview of studies addressing cognition and describes potential underlying mechanisms for the reported effects. Short-term VNS has an effect on verbal memory recognition when administered at the correct timing and dosage. Chronic VNS resulted into a positive effect on the cognitive status in an Alzheimer population. Positive effect of chronic VNS in epilepsy or depression patients on global cognitive functioning are less convincing. Neither do the results reveal a negative effect which has major implications for chronic treatment of neurology patients. A cascade of neurochemical processes put in motion by changes in NE concentrations in reaction to stimulation of the vagal nerve may underlie the VNS-induced effects on cognition and memory. In Alzheimer pathology, NE may act as an anti-inflammatory agent on brainstem nuclei. PMID:24858008

  4. Carotid Space Mass Proximal to Vagus Nerve Causing Asystole and Syncope.

    PubMed

    Leviter, Julie; Wiznia, Daniel H

    2016-01-01

    Manipulation of vagal nerve rootlets, whether surgical or through mass effect of a neoplasm, can result in asystole and hypotension, accompanied by ST depression and right bundle branch block. There are few case reports of a neoplasm causing these effects, and this case describes a patient with such a mass presenting with syncopal episodes. A 43-year-old man with a past medical history of HIV, bipolar disorder, and epilepsy was admitted to the neurology service for a video electroencephalogram (vEEG) to characterize syncopal episodes that were felt to be epileptic in origin. During the study, he experienced symptoms of his typical aura, which correlated with a transient symptomatic high degree AV block on telemetry, and an absence of epileptic findings on vEEG. Magnetic Resonance Imaging (MRI) of the brain showed a mass in the left posterior carotid space at the skull base. The patient underwent permanent dual chamber MRI-compatible pacemaker placement for his heart block. His syncopal episodes resolved, but presyncopal symptoms persisted. We discuss the presentation and treatment of vagal neoplasms. PMID:27516914

  5. Carotid Space Mass Proximal to Vagus Nerve Causing Asystole and Syncope

    PubMed Central

    2016-01-01

    Manipulation of vagal nerve rootlets, whether surgical or through mass effect of a neoplasm, can result in asystole and hypotension, accompanied by ST depression and right bundle branch block. There are few case reports of a neoplasm causing these effects, and this case describes a patient with such a mass presenting with syncopal episodes. A 43-year-old man with a past medical history of HIV, bipolar disorder, and epilepsy was admitted to the neurology service for a video electroencephalogram (vEEG) to characterize syncopal episodes that were felt to be epileptic in origin. During the study, he experienced symptoms of his typical aura, which correlated with a transient symptomatic high degree AV block on telemetry, and an absence of epileptic findings on vEEG. Magnetic Resonance Imaging (MRI) of the brain showed a mass in the left posterior carotid space at the skull base. The patient underwent permanent dual chamber MRI-compatible pacemaker placement for his heart block. His syncopal episodes resolved, but presyncopal symptoms persisted. We discuss the presentation and treatment of vagal neoplasms. PMID:27516914

  6. Therapeutic effect of vagus nerve stimulation on depressive-like behavior, hyperglycemia and insulin receptor expression in Zucker fatty rats.

    PubMed

    Li, Shaoyuan; Zhai, Xu; Rong, Peijing; McCabe, Michael F; Wang, Xing; Zhao, Jingjun; Ben, Hui; Wang, Shuxing

    2014-01-01

    Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naïve (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naïve ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naïve ZDF rats is lower than in naïve ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation. PMID:25365428

  7. Axonal transport of muscarinic cholinergic receptors in rat vagus nerve: high and low affinity agonist receptors move in opposite directions and differ in nucleotide sensitivity

    SciTech Connect

    Zarbin, M.A.; Wamsley, J.K.; Kuhar, M.J.

    1982-07-01

    The presence and transport of muscarinic cholinergic binding sites have been detected in the rat vagus nerve. These binding sites accumulate both proximal and distal to ligatures in a time-dependent manner. The results of double ligature and colchicine experiments are compatible with the notion that the anterogradely transported binding sites move by fast transport. Most of the sites accumulating proximal to ligatures bind the agonist carbachol with high affinity, while most of the sites accumulating distally bind carbachol with a low affinity. Also, the receptors transported in the anterograde direction are affected by a guanine nucleotide analogue (GppNHp), while those transported in the retrograde direction are less, or not, affected. The bulk of the sites along the unligated nerve trunk bind carbachol with a low affinity and are less sensitive to GppNHp modulation than the anterogradely transported sites. These results suggest that some receptors in the vagus may undergo axonal transport in association with regulatory proteins and that receptor molecules undergo changes in their binding and regulatory properties during their life cycle. These data also support the notion that the high and low affinity agonist form of the muscarinic receptor represent different modulated forms of a single receptor molecule.

  8. Utility of a Novel Biofeedback Device for Within-Breath Modulation of Heart Rate in Rats: A Quantitative Comparison of Vagus Nerve vs. Right Atrial Pacing

    PubMed Central

    O'Callaghan, Erin L.; Chauhan, Ashok S.; Zhao, Le; Lataro, Renata M.; Salgado, Helio C.; Nogaret, Alain; Paton, Julian F. R.

    2016-01-01

    In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA. PMID:26869940

  9. Utility of a Novel Biofeedback Device for Within-Breath Modulation of Heart Rate in Rats: A Quantitative Comparison of Vagus Nerve vs. Right Atrial Pacing.

    PubMed

    O'Callaghan, Erin L; Chauhan, Ashok S; Zhao, Le; Lataro, Renata M; Salgado, Helio C; Nogaret, Alain; Paton, Julian F R

    2016-01-01

    In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA. PMID:26869940

  10. [Changes in the afferent activity of the vagus nerve and the rectal temperature in rats following Escherichia coli endotoxin administration].

    PubMed

    Lapsha, V I; Lukashenko, T M; Utkina, L N; Gurin, V N

    2001-10-01

    In anaesthetised rats, i.p. administration of the Echerichia coli lipopolysaccharide in doses 5 mcg/kg (LPS) increased afferent activity of the cervical vagus, whereas 100 and 1000 mcg/kg doses inhibited the afferent discharges. Pyrogen-free saline (PFS) did not alter the activity. Rectal temperature (RT) was decreased by the PFS and by large doses of the LPS. Sodium salicylate administration prevented the effects. PMID:11767451

  11. Intermittent electrical stimulation of the right cervical vagus nerve in salt-sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology

    PubMed Central

    Annoni, Elizabeth M; Xie, Xueyi; Lee, Steven W; Libbus, Imad; KenKnight, Bruce H; Osborn, John W; Tolkacheva, Elena G

    2015-01-01

    Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases. PMID:26265746

  12. Auricular vagus nerve stimulation promotes functional recovery and enhances the post-ischemic angiogenic response in an ischemia/reperfusion rat model.

    PubMed

    Jiang, Ying; Li, Longling; Ma, Jingxi; Zhang, Lina; Niu, Fei; Feng, Tao; Li, Changqing

    2016-07-01

    Electrical stimulation of the vagus nerve, which has been used to treat epilepsy patients since 1997, also enhances long-term restoration after central nervous system (CNS) injury. Angiogenesis is a complex restorative mechanism that occurs in response to ischemic stroke, and it positively affects the recovery of neurological functions in a rat model of stroke. The aims of our study were to determine whether auricular vagus nerve stimulation (aVNS) promoted functional recovery and enhanced angiogenesis in the ischemic boundary following ischemia/reperfusion and to uncover the possible molecular mechanisms that are involved. Adult male Sprague-Dawley (SD) rats underwent transient middle cerebral artery occlusion (tMCAO) surgery and received repeated electrical stimulation of the left cavum concha starting 30 min after ischemia. For the following 21 days, we evaluated functional recovery at different time points using neurological deficit scores, the beam-walking test and the staircase test. The infarct volume was measured using TTC staining at 24 h post reperfusion, neuronal survival in the ischemic penumbra was assessed using hematoxylin and eosin (HE) staining. Microvessel density and endothelial cell proliferation in the ischemic boundary were assessed using immunofluorescence. The expression levels of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) in the ischemic penumbra were also evaluated. Our results showed that aVNS had significant neuroprotective effects and enhanced angiogenesis, which was demonstrated by improvements in the behavioral scores and brain histopathology, including increased levels of microvessel density and endothelial cell proliferation surrounding the infarct area. Furthermore, BDNF, eNOS and VEGF were expressed at higher levels in the I/R + aVNS group than in the I/R group or the I/R + sham aVNS group (p < 0.05). Our findings suggest that repeated a

  13. TRPV1-dependent regulation of synaptic activity in the mouse dorsal motor nucleus of the vagus nerve

    PubMed Central

    Anwar, Imran J.; Derbenev, Andrei V.

    2013-01-01

    The dorsal motor nucleus of the vagus (DMV) is a key integrative point of the parasympathetic neuronal network localized in the dorsal vagal complex. Activity of neurons in the DMV is closely regulated by synaptic inputs, and regulation of excitatory and inhibitory synapsis by transient receptor potential vanilloid type 1 (TRPV1) has been demonstrated. Activation of TRPV1 by heat, protons, endovanilloids, endocannabinoids, and inflammatory mediators is well established. In our study we hypothesized that TRPV1 contributes to the synaptic transmission of DMV neurons at physiological range of temperature without additional stimuli. Using whole-cell patch-clamp recordings we evaluated the effect of a rapid increase of temperature on excitatory and inhibitory neurotransmission and the contribution of TRPV1 to this response. Rapid increase of temperature from 25 to 37°C increased the frequency of miniature excitatory post-synaptic currents (mEPSC) by 351.7%. The frequency of miniature inhibitory post-synaptic currents (mIPSC) also increased by 184.7%. 5′-iodoresiniferatoxin (5′-iRFT), a selective TRPV1 antagonist, prevented the increase of mEPSC and mIPSC frequency. In summary, our data demonstrate that at physiological range of temperature TRPV1 contributes to presynaptic neurotransmission of DMV neurons. PMID:24379754

  14. Electrical Stimulation at the ST36 Acupoint Protects against Sepsis Lethality and Reduces Serum TNF Levels through Vagus Nerve- and Catecholamine-Dependent Mechanisms.

    PubMed

    Villegas-Bastida, Albino; Torres-Rosas, Rafael; Arriaga-Pizano, Lourdes Andrea; Flores-Estrada, Javier; Gustavo-Acosta, Altamirano; Moreno-Eutimio, Mario Adan

    2014-01-01

    Electrical vagus nerve (VN) stimulation during sepsis attenuates tumor necrosis factor (TNF) production through the cholinergic anti-inflammatory pathway, which depends on the integrity of the VN and catecholamine production. To characterize the effect of electroacupuncture at ST36 (EA-ST36) on serum TNF, IL-6, nitrite, and HMGB1 levels and survival rates, based on VN integrity and catecholamine production, a sepsis model was induced in rats using cecal ligation and puncture (CLP). The septic rats were subsequently treated with EA-ST36 (CLP+ST36), and serum samples were collected and analyzed for cytokines levels. The serum TNF, IL-6, nitrite, and HMGB1 levels in the CLP+ST36 group were significantly lower compared with the group without treatment, the survival rates were significantly higher (P < 0.05), and the acute organ injury induced by CLP was mitigated by EA-ST36; however, when subdiaphragmatic vagotomy was performed, the serum levels of TNF in the CLP+ST36 group did not show a significant difference compared with the group without electrostimulation, and, similarly, no significant difference in serum TNF levels was found under the pharmacological blockade of catecholamines. These results suggest that in rats with CLP sepsis models EA-ST36 reduces serum TNF levels through VN- and atecholamine-dependent mechanisms. PMID:25057275

  15. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.

    PubMed

    Bravo, Javier A; Forsythe, Paul; Chew, Marianne V; Escaravage, Emily; Savignac, Hélène M; Dinan, Timothy G; Bienenstock, John; Cryan, John F

    2011-09-20

    There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression. PMID:21876150

  16. Low-Level Vagus Nerve Stimulation Reverses Cardiac Dysfunction and Subcellular Calcium Handling in Rats With Post-Myocardial Infarction Heart Failure.

    PubMed

    Zhang, Yunhe; Chen, Ao; Song, Lei; Li, Min; Luo, Zhangyuan; Zhang, Wenzan; Chen, Yingmin; He, Ben

    2016-05-25

    Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL-VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), Na(+)-Ca(2+) exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL-VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF. PMID:27181040

  17. The use of antagonists to characterize the receptors mediating depolarization of the rat isolated vagus nerve by alpha, beta-methylene adenosine 5'-triphosphate.

    PubMed Central

    Trezise, D. J.; Kennedy, I.; Humphrey, P. P.

    1994-01-01

    1. We have previously found that the P2x-purinoceptor agonist, alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-methylene ATP), depolarizes the rat cervical vagus nerve, measured with a 'grease-gap' extracellular recording technique. This effect was attenuated by the P2 purinoceptor antagonist, suramin. In the present study we have investigated in more detail the antagonism produced by suramin and have also investigated the actions of two other putative P2 purinoceptor antagonists, cibacron blue and pyridoxal-phosphate-6-azophenyl-2', 5'-disulphonic acid (iso-PPADS). Furthermore, we have studied the interactions between suramin and cibacron blue or iso-PPADS in an attempt to determine whether these antagonists act at a common receptor site. 2. Suramin (1 x 10(-5)-1 x 10(-4) M) produced reversible, concentration-related rightward displacements of the concentration-effect curve to alpha, beta-methylene ATP. Schild analysis of this antagonism yielded a pA2 value of 5.90 with a slope value of 0.47. 3. Cibacron blue (3 x 10(-5)-1 x 10(-4) M) also antagonized depolarizations induced by alpha, beta-methylene ATP. The antagonistic effects of cibacron blue were slow to reach equilibrium but could be readily reversed on washout. At low concentrations for antagonism, cibacron blue (1 x 10(-5) M and 3 x 10(-5) M) produced enhancement of the maximal response to alpha, beta-methylene ATP. At the highest concentration tested (1 x 10(-4) M) the concentration-effect curve to alpha, beta-methylene ATP was shifted to the right in a parallel manner, yielding a pKB estimate of 4.96.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8032652

  18. Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans

    PubMed Central

    Frangos, Eleni; Ellrich, Jens; Komisaruk, Barry R.

    2014-01-01

    Background Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as to whether or not the ABVN projects to the NTS in humans. Objective To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the “classical” central vagal projections in humans. Methods Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem p<0.01, forebrain p<0.05), followed by a whole-brain analysis (corrected, p< 0.05). Results Cymba conchae stimulation, compared to earlobe (control) stimulation, produced significant activation of the “classical” central vagal projections, e.g., widespread activity in the ipsilateral nucleus of the solitary tract, bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral activation of the paracentral lobule was also observed. Deactivations were observed bilaterally in the hippocampus and hypothalamus. Conclusion These findings provide evidence in humans that the central projections of the ABVN are consistent with the “classical” central vagal projections and can be accessed non-invasively via the external ear. PMID:25573069

  19. [Surfactant and water balance of lung in intracerebral hemorrhage at conditions of capsaicin blockade of vagus nerve].

    PubMed

    Urakova, M A; Bryndina, I G

    2015-03-01

    It is known that intracranial hemorrhage (ICH) is accompanied by the development of neurogenic pulmonary edema and insufficiency of surfactant function. The present study was undertaken for evaluation of the role of vagal afferents in the mechanisms of ICH effects on pulmonary surfactant and water balance of the lung. We explored the surface activity and biochemical composition of surfactant, as well as blood supply, total, intravascular and extravascular fluid content in lung after ICH, simulated by intraventricular administration of autologous blood against the background of bilateral blockade of capsaicin-sensitive vagal affere its. The blockade was caused by the capsaicin application (50 mcmol) on the cervical part of the nerves. Intracerebralhemorrhage was accompanied by the decrease of surfactant activity which appeared by the enhancement of minimal, maximal and static surface tension of bronchoalveolar lavage fluid (BAL), the reduction of total phospholipids including their main fraction phosphatidylcholine, the increase of lysophosphatidyicholine content and hyperhydration of the lung. The level of total proteins in BAL elevated, confirmed the enhanced permeability of the alveolar-blood barrier. The exhaustion of neuropeptides in capsaicin-sensitive vagal afferents led to the partial restoration of surface active properties of lung, normalization of phospholipids and protein contents and water balance parameters. The obtained results suggest that capsaicin-sensitive vagal afferents play a pivotal role in the disturbances of surfactant function and water balance of the lung after ICH. PMID:26016324

  20. Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor.

    PubMed

    Kimura, Kumi; Tanida, Mamoru; Nagata, Naoto; Inaba, Yuka; Watanabe, Hitoshi; Nagashimada, Mayumi; Ota, Tsuguhito; Asahara, Shun-ichiro; Kido, Yoshiaki; Matsumoto, Michihiro; Toshinai, Koji; Nakazato, Masamitsu; Shibamoto, Toshishige; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2016-03-15

    Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via α7-nicotinic acetylcholine receptors (α7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity. Indeed, central insulin-mediated hepatic IL-6/STAT3 activation and gluconeogenic gene suppression were impeded in mice with hepatic vagotomy, pharmacological cholinergic blockade, or α7-nAchR deficiency. In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines. These findings suggest that dysregulation of the α7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity. PMID:26947072

  1. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities.

    PubMed

    Huf, Roger L; Mamelak, Adam; Kneedy-Cayem, Kara

    2005-05-01

    Treating seizures among patients with mental retardation/developmental disabilities (MR/DD) is difficult owing in large part to the presence of additional comorbidities and the resulting need for polytherapy. Therefore, a nonpharmacological treatment option is needed for this population. This prospective, open-label study documented the long-term outcome of 40 low-IQ (<70) patients living in long-term care facilities who received vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Subjects were seen every 1 to 3 months by their neurologist (R.H.). Seizure frequency, antiepileptic medication, and quality-of-life information were documented preimplantation and quarterly thereafter through 2 years. The surgery and therapy were well tolerated. Seizures were reduced by at least 50% for 11 subjects. Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years. According to caregiver reports, overall quality of life improved for the majority of subjects; also, using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores. VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities. PMID:15820352

  2. Magnetic Resonance Imaging Evidence of Varicella Zoster Virus Polyneuropathy: Involvement of the Glossopharyngeal and Vagus Nerves Associated With Ramsay Hunt Syndrome.

    PubMed

    Gunbey, Hediye Pinar; Kutlar, Gokhan; Aslan, Kerim; Sayit, Asli Tanrivermis; Incesu, Lutfi

    2016-05-01

    The involvement of lower cranial nerve palsies is less frequent in Ramsay Hunt syndrome caused by varicella zoster virus (VZV). The authors report 1 of extremely rare patients of radiologically proven polyneuropathy of VZV infection with magnetic resonance imaging findings of VII, IX, and X cranial nerve involvement is a 62-year-old female patient, who initially presented with Ramsay Hunt syndrome. Varicella zoster virus infection should be considered even in patients who show unilateral palsy of the lower cranial nerves associated with laryngeal paralysis. Thin-section T2W and T1W images with a contrast agent should be added to the imaging protocol to show the subtle involvement. PMID:27092925

  3. A new method for labelling saxitoxin and its binding to non-myelinated fibres of the rabbit vagus, lobster walking leg, and garfish olfactory nerves.

    PubMed Central

    Ritchie, J M; Rogart, R B; Strichartz, G R

    1976-01-01

    1. A new method of labelling saxitoxin (STX) is described, based on transfer of tritium from tritiated water to the toxin. 2. The radiochemical purity of the labelled toxin has been directly determined, rather than being based on indirect biochemical means, as in previous experiments with Wilzbach-labelled STX and TTX. 3. The specific activity of the labelled toxin, 66 d..m.f-mole-1, corresponds with one tritium atom per molecule STX, an improvement of about 300-fold over other means of labelling TTX and STX. 4. The binding of this toxin to rabbit, lobster and garfish olfactory nerve fibres has been re-examined. 5. The density of sodium channels calculated on the basis of the binding of the toxin is about four to six-times the values previously reported. PMID:978583

  4. Vagus Nerve Stimulation for Treating Epilepsy

    MedlinePlus

    ... is the world’s largest association of neurologists and neuroscience professionals. Neurologists are doctors who identify and treat ... in these children. It also affects thinking and learning ability. Weak evidence shows VNS may help as ...

  5. Role of the vegus nerve in epilepsy (image)

    MedlinePlus

    The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. ...

  6. Hepatic nerve growth factor induced by iron overload triggers defenestration in liver sinusoidal endothelial cells.

    PubMed

    Addo, Lynda; Tanaka, Hiroki; Yamamoto, Masayo; Toki, Yasumichi; Ito, Satoshi; Ikuta, Katsuya; Sasaki, Katsunori; Ohtake, Takaaki; Torimoto, Yoshihiro; Fujiya, Mikihiro; Kohgo, Yutaka

    2015-01-01

    The fenestrations of liver sinusoidal endothelial cells (LSECs) play important roles in the exchange of macromolecules, solutes, and fluid between blood and surrounding liver tissues in response to hepatotoxic drugs, toxins, and oxidative stress. As excess iron is a hepatotoxin, LSECs may be affected by excess iron. In this study, we found a novel link between LSEC defenestration and hepatic nerve growth factor (NGF) in iron-overloaded mice. By Western blotting, NGF was highly expressed, whereas VEGF and HGF were not, and hepatic NGF mRNA levels were increased according to digital PCR. Immunohistochemically, NGF staining was localized in hepatocytes, while TrkA, an NGF receptor, was localized in LSECs. Scanning electron microscopy revealed LSEC defenestration in mice overloaded with iron as well as mice treated with recombinant NGF. Treatment with conditioned medium from iron-overloaded primary hepatocytes reduced primary LSEC fenestrations, while treatment with an anti-NGF neutralizing antibody or TrkA inhibitor, K252a, reversed this effect. However, iron-loaded medium itself did not reduce fenestration. In conclusion, iron accumulation induces NGF expression in hepatocytes, which in turn leads to LSEC defenestration via TrkA. This novel link between iron and NGF may aid our understanding of the development of chronic liver disease. PMID:25460199

  7. Leptin Receptor Signaling in the Hypothalamus Regulates Hepatic Autonomic Nerve Activity via Phosphatidylinositol 3-Kinase and AMP-Activated Protein Kinase

    PubMed Central

    Yamamoto, Naoki; Morgan, Donald A.; Kurata, Yasutaka; Shibamoto, Toshishige

    2015-01-01

    Leptin action in the brain has emerged as an important regulator of liver function independently from its effects on food intake and body weight. The autonomic nervous system plays a key role in the regulation of physiological processes by leptin. Here, we used direct recording of nerve activity from sympathetic or vagal nerves subserving the liver to investigate how brain action of leptin controls hepatic autonomic nerve activity. Intracerebroventricular (ICV) administration of leptin activated hepatic sympathetic traffic in rats and mice in dose- and receptor-dependent manners. The hepatic sympatho-excitatory effects of leptin were also observed when leptin was microinjected directly into the arcuate nucleus (ARC), but not into the ventromedial hypothalamus (VMH). Moreover, using pharmacological and genetic approaches, we show that leptin-induced increase in hepatic sympathetic outflow depends on PI3K but not AMP-activated protein kinase (AMPK), STAT3, or ERK1/2. Interestingly, ICV leptin also increased hepatic vagal nerve activity in rats. We show that this response is reproduced by intra-ARC, but not intra-VMH, leptin administration and requires PI3K and AMPK. We conclude that central leptin signaling conveys the information to the liver through the sympathetic and parasympathetic branches of the autonomic nervous system. Our data also provide important insight into the molecular events underlying leptin's control of hepatic autonomic nerve activity by implicating PI3K and AMPK pathways. PMID:25589743

  8. Properties of postganglionic sympathetic neurons with axons in the right thoracic vagus.

    PubMed

    Bałkowiec, A; Szulczyk, P

    1992-01-01

    The resting and reflex-evoked activities of single postganglionic sympathetic neurons with axons in the right thoracic vagus were tested in chloralose-anaesthetized cats. The properties of a majority of neurons were found to be similar. Cardiac- and inspiration-related rhythmicities were present in the resting activity of sympathetic neurons. Their resting activity was not affected by hyperventilation which abolished phrenic nerve discharges. Systemic hypoxia (2 min; 8% O2 in N2) increased the activity of the neurons more effectively in the deafferented state than when both sinus nerves remained intact. Injection of 0.1 ml 1 M sodium bicarbonate saturated with CO2, which activates peripheral chemoreceptors in the right or left carotid sinus, usually evoked a decrease in sympathetic activity in animals with both sinus nerves intact. We concluded that activation of peripheral chemoreceptors may inhibit the activity of the sympathetic neurons with axons in the right thoracic vagus. We suggest that the described sympathetic neurons may be a functionally homogeneous population which may innervate the conducting system of the heart. The close localization of sympathetic and parasympathetic axons in the vagus nerve may facilitate sympathetic-parasympathetic interaction at the level of their endings in the heart. PMID:1584420

  9. Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nerve-gastric channel pathway

    PubMed Central

    Wang, Hao; Liu, Wen-Jian; Shen, Guo-Ming; Zhang, Meng-Ting; Huang, Shun; He, Ying

    2015-01-01

    in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVC-vagus-gastric neural pathway. PMID:26730159

  10. Hepatitis

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  11. Disorders of Cranial Nerves IX and X

    PubMed Central

    Erman, Audrey B.; Kejner, Alexandra E.; Hogikyan, Norman D.; Feldman, Eva L.

    2014-01-01

    The glossopharyngeal and vagus nerves mediate the complex interplay between the many functions of the upper aerodigestive tract. Defects may occur anywhere from the brainstem to the peripheral nerve and can result in significant impairment in speech, swallowing, and breathing. Multiple etiologies can produce symptoms. This review will broadly examine the normal functions, clinical examination, and various pathologies of cranial nerves IX and X. PMID:19214937

  12. The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake

    PubMed Central

    Cooper, Martin E; Regnell, Simon E

    2014-01-01

    The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation between hepatic ATP content and insulin resistance. A decreased hepatic ATP/AMP ratio increases food intake by signals via the vagus nerve to the brain. The hepatic cannabinoid system is highly upregulated in obesity, and the effects of hepatic CB1R activation include increased activity of lipogenic and gluconeogenic transcription factors. Thus, blockade of hepatic CB1Rs could contribute significantly to the weight-reducing and insulin-sensitizing effects of CB1R antagonists. Additionally, upregulation of the hepatic CB1R may contribute to chronic liver inflammation, fibrosis and cirrhosis from causes including obesity, alcoholism and viral hepatitis. Peripheral CB1R antagonists induce weight loss and metabolic improvements in obese rodents; however, as there is evidence that hepatic CB1Rs are predominately intracellular, due to high intrinsic clearance, many drugs may not effectively block these receptors and therefore have limited efficacy. Hepatoselective CB1R antagonists may be effective at reducing hepatic steatosis, insulin resistance and bodyweight in obese, diabetic patients, with far fewer side-effects than first-generation CB1R antagonists. Additionally, such compounds may be effective in treating inflammatory liver disease, such as non-alcoholic steatohepatitis, reducing the likelihood of disease progression to cirrhosis or cancer. PMID:23452341

  13. The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake.

    PubMed

    Cooper, Martin E; Regnell, Simon E

    2014-01-01

    The cannabinoid 1 receptor (CB1R) has a well-established role in appetite regulation. Central CB1R antagonists, notably rimonabant, induced weight loss and improved the metabolic profile in obese individuals, but were discontinued due to psychiatric side-effects. The CB1R is also expressed peripherally, where its effects include promotion of liver fat accumulation, which consumes ATP. Type 2 diabetes in obese subjects is linked to excess liver fat, whilst there is a negative correlation between hepatic ATP content and insulin resistance. A decreased hepatic ATP/AMP ratio increases food intake by signals via the vagus nerve to the brain. The hepatic cannabinoid system is highly upregulated in obesity, and the effects of hepatic CB1R activation include increased activity of lipogenic and gluconeogenic transcription factors. Thus, blockade of hepatic CB1Rs could contribute significantly to the weight-reducing and insulin-sensitizing effects of CB1R antagonists. Additionally, upregulation of the hepatic CB1R may contribute to chronic liver inflammation, fibrosis and cirrhosis from causes including obesity, alcoholism and viral hepatitis. Peripheral CB1R antagonists induce weight loss and metabolic improvements in obese rodents; however, as there is evidence that hepatic CB1Rs are predominately intracellular, due to high intrinsic clearance, many drugs may not effectively block these receptors and therefore have limited efficacy. Hepatoselective CB1R antagonists may be effective at reducing hepatic steatosis, insulin resistance and bodyweight in obese, diabetic patients, with far fewer side-effects than first-generation CB1R antagonists. Additionally, such compounds may be effective in treating inflammatory liver disease, such as non-alcoholic steatohepatitis, reducing the likelihood of disease progression to cirrhosis or cancer. PMID:23452341

  14. Hepatitis

    MedlinePlus

    ... has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool to ... risk for severe disease. Others A variety of viruses can affect the liver Signs and Symptoms Hepatitis ...

  15. Neuromuscular Ultrasound of Cranial Nerves

    PubMed Central

    Tawfik, Eman A.; Cartwright, Michael S.

    2015-01-01

    Ultrasound of cranial nerves is a novel subdomain of neuromuscular ultrasound (NMUS) which may provide additional value in the assessment of cranial nerves in different neuromuscular disorders. Whilst NMUS of peripheral nerves has been studied, NMUS of cranial nerves is considered in its initial stage of research, thus, there is a need to summarize the research results achieved to date. Detailed scanning protocols, which assist in mastery of the techniques, are briefly mentioned in the few reference textbooks available in the field. This review article focuses on ultrasound scanning techniques of the 4 accessible cranial nerves: optic, facial, vagus and spinal accessory nerves. The relevant literatures and potential future applications are discussed. PMID:25851889

  16. Intraoperative vagal nerve monitoring.

    PubMed

    Leonetti, J P; Jellish, W S; Warf, P; Hudson, E

    1996-08-01

    A variety of benign and malignant neoplasms occur in the superior cervical neck, parapharyngeal space or the infratemporal fossa. The surgical resection of these lesions may result in postoperative iatrogenic injury to the vagus nerve with associated dysfunctional swallowing and airway protection. Anatomic and functional preservation of this critical cranial nerve will contribute to a favorable surgical outcome. Fourteen patients with tumors of the cervical neck or adjacent skull base underwent intraoperative vagal nerve monitoring in an attempt to preserve neural integrity following tumor removal. Of the 11 patients with anatomically preserved vagal nerves in this group, seven patients had normal vocal cord mobility following surgery and all 11 patients demonstrated normal vocal cord movement by six months. In an earlier series of 23 patients with tumors in the same region who underwent tumor resection without vagal nerve monitoring, 18 patients had anatomically preserved vagal nerves. Within this group, five patients had normal vocal cord movement at one month and 13 patients demonstrated normal vocal cord movement at six months. This paper will outline a technique for intraoperative vagal nerve monitoring utilizing transcricothyroid membrane placement of bipolar hook-wire electrodes in the vocalis muscle. Our results with the surgical treatment of cervical neck and lateral skull base tumors for patients with unmonitored and monitored vagal nerves will be outlined. PMID:8828272

  17. Hepatitis

    MedlinePlus

    ... be serious. Some can lead to scarring, called cirrhosis, or to liver cancer. Sometimes hepatitis goes away by itself. If it does not, it can be treated with drugs. Sometimes hepatitis lasts a lifetime. Vaccines can help prevent some viral forms.

  18. HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.

    PubMed

    Miranda, Rosiane A; Torrezan, Rosana; de Oliveira, Júlio C; Barella, Luiz F; da Silva Franco, Claudinéia C; Lisboa, Patrícia C; Moura, Egberto G; Mathias, Paulo C F

    2016-07-01

    Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity. PMID:27113853

  19. Cranial Nerves IX, X, XI, and XII

    PubMed Central

    Sanders, Richard D.

    2010-01-01

    This article concludes the series on cranial nerves, with review of the final four (IX–XII). To summarize briefly, the most important and common syndrome caused by a disorder of the glossopharyngeal nerve (craniel nerve IX) is glossopharyngeal neuralgia. Also, swallowing function occasionally is compromised in a rare but disabling form of tardive dyskinesia called tardive dystonia, because the upper motor portion of the glossopharyngel nerve projects to the basal ganglia and can be affected by lesions in the basal ganglia. Vagus nerve funtion (craniel nerve X) can be compromised in schizophrenia, bulimia, obesity, and major depression. A cervical lesion to the nerve roots of the spinal accessory nerve (craniel nerve XI) can cause a cervical dystonia, which sometimes is misdiagnosed as a dyskinesia related to neuroleptic use. Finally, unilateral hypoglossal (craniel nerve XII) nerve palsy is one of the most common mononeuropathies caused by brain metastases. Supranuclear lesions of cranial nerve XII are involved in pseudobulbar palsy and ALS, and lower motor neuron lesions of cranial nerve XII can also be present in bulbar palsy and in ALS patients who also have lower motor neuron involvement. This article reviews these and other syndromes related to cranial nerves IX through XII that might be seen by psychiatry. PMID:20532157

  20. On the vagal cardiac nerves, with special reference to the early evolution of the head-trunk interface.

    PubMed

    Higashiyama, Hiroki; Hirasawa, Tatsuya; Oisi, Yasuhiro; Sugahara, Fumiaki; Hyodo, Susumu; Kanai, Yoshiakira; Kuratani, Shigeru

    2016-09-01

    The vagus nerve, or the tenth cranial nerve, innervates the heart in addition to other visceral organs, including the posterior visceral arches. In amniotes, the anterior and posterior cardiac branches arise from the branchial and intestinal portions of the vagus nerve to innervate the arterial and venous poles of the heart, respectively. The evolution of this innervation pattern has yet to be elucidated, due mainly to the lack of morphological data on the vagus in basal vertebrates. To investigate this topic, we observed the vagus nerves of the lamprey (Lethenteron japonicum), elephant shark (Callorhinchus milii), and mouse (Mus musculus), focusing on the embryonic patterns of the vagal branches in the venous pole. In the lamprey, no vagus branch was found in the venous pole throughout development, whereas the arterial pole was innervated by a branch from the branchial portion. In contrast, the vagus innervated the arterial and venous poles in the mouse and elephant shark. Based on the morphological patterns of these branches, the venous vagal branches of the mouse and elephant shark appear to belong to the intestinal part of the vagus, implying that the cardiac nerve pattern is conserved among crown gnathostomes. Furthermore, we found a topographical shift of the structures adjacent to the venous pole (i.e., the hypoglossal nerve and pronephros) between the extant gnathostomes and lamprey. Phylogenetically, the lamprey morphology is likely to be the ancestral condition for vertebrates, suggesting that the evolution of the venous branch occurred early in the gnathostome lineage, in parallel with the remodeling of the head-trunk interfacial domain during the acquisition of the neck. J. Morphol. 277:1146-1158, 2016. © 2016 Wiley Periodicals, Inc. PMID:27216138

  1. Sex differences in morphometric aspects of the peripheral nerves and related diseases

    PubMed Central

    Moriyama, Hiroshi; Hayashi, Shogo; Inoue, Yuriko; Itoh, Masahiro; Otsuka, Naruhito

    2016-01-01

    BACKGROUND: The elucidation of the relationship between the morphology of the peripheral nerves and the diseases would be valuable in developing new medical treatments on the assumption that characteristics of the peripheral nerves in females are different from those in males. METHODS: We used 13 kinds of the peripheral nerve. The materials were obtained from 10 Japanese female and male cadavers. We performed a morphometric analysis of nerve fibers. We estimated the total number of myelinated axons, and calculated the average transverse area and average circularity ratio of myelinated axons in the peripheral nerves. RESULTS: There was no statistically significant difference in the total number, average transverse area, or average circularity ratio of myelinated axons between the female and male specimens except for the total number of myelinated axons in the vestibular nerve and the average circularity ratio of myelinated axons in the vagus nerve. CONCLUSIONS: The lower number of myelinated axons in the female vestibular nerve may be one of the reasons why vestibular disorders have a female preponderance. Moreover, the higher average circularity ratio of myelinated axons in the male vagus nerve may be one reason why vagus nerve activity to modulate pain has a male preponderance. PMID:27589511

  2. Arnold’s nerve cough reflex: evidence for chronic cough as a sensory vagal neuropathy

    PubMed Central

    Gibson, Peter G.; Birring, Surinder S.

    2014-01-01

    Arnold’s nerve ear-cough reflex is recognised to occur uncommonly in patients with chronic cough. In these patients, mechanical stimulation of the external auditory meatus can activate the auricular branch of the vagus nerve (Arnold’s nerve) and evoke reflex cough. This is an example of hypersensitivity of vagal afferent nerves, and there is now an increasing recognition that many cases of refractory or idiopathic cough may be due to a sensory neuropathy of the vagus nerve. We present two cases where the cause of refractory chronic cough was due to sensory neuropathy associated with ear-cough reflex hypersensitivity. In both cases, the cough as well as the Arnold’s nerve reflex hypersensitivity were successfully treated with gabapentin, a treatment that has previously been shown to be effective in the treatment of cough due to sensory laryngeal neuropathy (SLN). PMID:25383210

  3. Cobalt iontophoresis of sensory nerves in the rat lung.

    PubMed

    El-Bermani, A W; Chang, T L

    1979-02-01

    By iontophoretically introducing, first, cobalt and, subsequently, sulfide ions into the vagus nerve, it is possible to trace sensory nerves to their endings in the rat lung. Nerve fibers and terminals are found predominantly in the adventitia of the airways and blood vessels. Some nerves are found in the submucosa of the bronchi and bronchioles. Some are found in the cardiac muscle on the periphery of pulmonary veins, and a few nerves are seen to end among smooth muslces of the blood vessels and the airways. At least three types of nerve endings can be identified at the light microscopic level: (1) free nerve endings; (2) brush-like endings; (3) knob-like terminals. PMID:760496

  4. Heptadecapeptide gastrin in the vagal nerve.

    PubMed Central

    Uvnäs-Wallensten, K; Rehfeld, J F; Larsson, L I; Uvnäs, B

    1977-01-01

    Immunoreactive gastrin was present in vagal nerves from cats, dogs, and human beings. The abdominal portion of the vagus contained gastrin in amounts ranging from 16 to 273 pmol/g of nerve tissue (wet weight). The thoracic and cervical portion of the vagi contained only minute amounts of gastrin. Gel chromatography of extracts of human, canine, and feline abdominal vagi monitored by region-specific antisera against heptadecapeptide gastrin and triacontatriapeptide cholecystokinin revealed that the vagal gastrin immunoreactivity predominantly consisted of heptadecapeptide gastrin. In addition, the vagi contained small amounts of the NH2-terminal tridecapeptide gastrin fragment as well as of the putative biosynthetic gastrin precursors, components I and II. No cholecystokinin-like molecules were demonstrable. Immunocytochemical studies demonstrated gastrin-containing nerves in the intestinal wall. The nerves were found to be most numerous in the large and distal small intestine. These findings suggest that heptadecapeptide gastrin may represent a new vagal neurotransmitter. Images PMID:23537

  5. Nonrecurrent inferior laryngeal nerves and anatomical findings during thyroid surgery: report of three cases.

    PubMed

    Kato, Kumiko; Toriumi, Yasuo; Kamio, Makiko; Nogi, Hiroko; Shioya, Hisashi; Takeyama, Hiroshi

    2016-12-01

    A nonrecurrent inferior laryngeal nerve (NRILN) is found more frequently on the right side than on the left, and it is closely associated with an aberrant right subclavian artery. The presence of the aberrant right subclavian artery on preoperative computed tomography (CT) scan suggests NRILN; however, different types of branching locations and pathways exist. Here, we report three NRILN cases with different pathways where the vagus nerve arises more medial than usual and a review of the literature. Case 1: A 30-year-old Japanese female presented with papillary thyroid carcinoma. Preoperative CT scan revealed an aberrant right subclavian artery, and an operation was performed under suspicion of NRILN. During the operation, the vagus nerve was found to arise more medially than usual and two NRILNs originated from it at the level of the cricoid cartilage and at a more caudal position; the two NRILNs were preserved. Case 2: A 33-year-old Japanese female with a thyroid nodule of increased size underwent surgery. Preoperative CT scan revealed an aberrant right subclavian artery, which suggested NRILN. During the operation, the vagus nerve was identified to run more medially than usual and NRILN was found to originate at the level of the cricoid cartilage; NRILN was preserved. Case 3: A 78-year-old Japanese female underwent an operation with a diagnosis of papillary thyroid carcinoma. Preoperative CT scan showed an aberrant right subclavian artery. During the operation, NRILN was found to originate from the vagus nerve at the level of the lower pole of the thyroid gland, and the vagus nerve ran medial to the common carotid artery at the caudal level. PMID:27188389

  6. The VAGUS insight into psychosis scale--self-report and clinician-rated versions.

    PubMed

    Gerretsen, Philip; Remington, Gary; Borlido, Carol; Quilty, Lena; Hassan, Sabrina; Polsinelli, Gina; Teo, Celine; Mar, Wanna; Simon, Regina; Menon, Mahesh; Pothier, David D; Nakajima, Shinichiro; Caravaggio, Fernando; Mamo, David C; Rajji, Tarek K; Mulsant, Benoit H; Deluca, Vincenzo; Ganguli, Rohan; Pollock, Bruce G; Graff-Guerrero, Ariel

    2014-12-30

    The aim of this study was to develop self-report and clinician-rated versions of an insight scale that would be easy to administer, sensitive to small changes, and inclusive of the core dimensions of clinical insight into psychosis. Ten-item self-report (VAGUS-SR) and five-item clinician-rated (VAGUS-CR) scales were designed to measure the dimensions of insight into psychosis and evaluated in 215 and 140 participants, respectively (www.vagusonline.com). Tests of reliability and validity were performed. Both the VAGUS-SR and VAGUS-CR showed good internal consistency and reliability. They demonstrated good convergent and discriminant validity. Both versions were strongly correlated with one another and with the Schedule for the Assessment of Insight and Birchwood Insight Scale. Exploratory factor analyses identified three possible latent components of insight. The VAGUS-CR and VAGUS-SR are valid, reliable and easy to administer. They are build on previous insight scales with separate clinician-rated and self-report versions. The VAGUS-SR exhibited a multidimensional factor structure. Using a 10-point Likert scale for each item, the VAGUS has the capacity to detect small, temporally sensitive changes in insight, which is essential for intervention studies with neurostimulation or rapidly acting medications. PMID:25246410

  7. Vagal nerve stimulator: Evolving trends

    PubMed Central

    Ogbonnaya, Sunny; Kaliaperumal, Chandrasekaran

    2013-01-01

    Over three decades ago, it was found that intermittent electrical stimulation from the vagus nerve produces inhibition of neural processes, which can alter brain activity and terminate seizures. This paved way for the concept of vagal nerve stimulator (VNS). We describe the evolution of the VNS and its use in different fields of medicine. We also review the literature focusing on the mechanism of action of VNS producing desired effects in different conditions. PUBMED and EMBASE search was performed for ‘VNS’ and its use in refractory seizure management, depression, obesity, memory, and neurogenesis. VNS has been in vogue over for the past three decades and has proven to reduce the intensity and frequency of seizure by 50% in the management of refractory seizures. Apart from this, VNS has been shown to promote neurogenesis in the dentate gyrus of rat hippocampus after 48 hours of stimulation of the vagus nerve. Improvement has also been observed in non-psychotic major depression from a randomized trial conducted 7 years ago. The same concept has been utilized to alter behavior and cognition in rodents, and good improvement has been observed. Recent studies have proven that VNS is effective in obesity management in patients with depression. Several hypotheses have been postulated for the mechanism of action of VNS contributing to its success. VNS has gained significant popularity with promising results in epilepsy surgery and treatment-resistant depression. The spectrum of its use has also extended to other fields of medicine including obesity, memory, and neurogenesis, and there is still a viable scope for its utility in the future. PMID:23633829

  8. Gastroduodenal ulcer treated by pylorus and pyloric vagus-preservinggastrectomy

    PubMed Central

    Lu, Yun-Fu; Zhang, Xin-Xin; Zhao, Ge; Zhu, Qing-Hua

    1999-01-01

    AIM To evaluate the curative effect of pylorus and pyloric vagus-preserving gastrectomy (PPVPG) on peptic ulcer. METHODS Treating 132 cases of GU and DU with PPVPG, and com parative studies made with 24 cases treated with Billroth I (B I) and 20 cases with Billroth II (B II); advantages and shortcomings evaluated. RESULTS Not a single death after PPVPG. No recurrence of the disorder in the subsequent follow-up for an average of 6.5 years. Curative effect (visik I-&-II) 97.7%. Acidity reduction similar to that found in B I and B II, but 97.7% of the B I and all B II cases having more than second degree intestinal fluid reflux, in contrast to 7.1% in PPVPG cases. Dumping syndrome occurred in the B I and B II cases, none in PPVPG cases. With regard to gastric emptying, food digestion, absorption, body weight and life quality, PPVPG proved to be superior to Billroth procedure. CONCLUSION PPVPG has the advantages of conventional Billroth gastrectomy in reducing acid, removing ulcer focus, and at the same time preserves the pylorus and pyloric vagus for maintaining the normal gastric physiological function. Dumping syndrome, intestinal fluid reflux and other complications of conventional gastrectomy may be avoided. PMID:11819417

  9. Main trajectories of nerves that traverse and surround the tympanic cavity in the rat

    PubMed Central

    WEIJNEN, J. A. W. M.; SURINK, S.; VERSTRALEN, M. J. M.; MOERKERKEN, A.; DE BREE, G. J.; BLEYS, R. L. A. W.

    2000-01-01

    To guide surgery of nerves that traverse and surround the tympanic cavity in the rat, anatomical illustrations are required that are topographically correct. In this study, maps of this area are presented, extending from the superior cervical ganglion to the otic ganglion. They were derived from observations that were made during dissections using a ventral approach. Major blood vessels, bones, transected muscles of the tongue and neck and supra and infrahyoid muscles serve as landmarks in the illustrations. The course of the mandibular, facial, glossopharyngeal, vagus, accessory and hypoglossal nerves with their branches, and components of the sympathetic system, are shown and discussed with reference to data available in the literature. Discrepancies in this literature can be clarified and new data are presented on the trajectories of several nerves. The course of the tympanic nerve was established. This nerve originates from the glossopharyngeal nerve, enters the tympanic cavity, crosses the promontory, passes the tensor tympani muscle dorsally, and continues its route intracranially to the otic ganglion as the lesser petrosal nerve after intersecting with the greater petrosal nerve. Auricular branches of the glossopharyngeal and of the vagus nerve were noted. We also observed a pterygopalatine branch of the internal carotid nerve, that penetrates the tympanic cavity and courses across the promontory. PMID:11005717

  10. α-Synuclein pathology in the cranial and spinal nerves in Lewy body disease.

    PubMed

    Nakamura, Keiko; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Toyoshima, Yasuko; Kakita, Akiyoshi; Takahashi, Hitoshi; Yamada, Masahito; Wakabayashi, Koichi

    2016-06-01

    Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA. PMID:26563477

  11. Detection of single unit activity from the rat vagus using cluster analysis of principal components.

    PubMed

    Horn, Charles C; Friedman, Mark I

    2003-01-30

    In vivo recordings from subdiaphragmatic vagal afferent nerves generally lack the resolution to distinguish single unit activity. Several methods for data acquisition and analysis were combined to produce a high degree of reliability in recording electrophysiological signals from gastrointestinal and hepatic afferent fibers in the rat. Recordings with low noise were achieved by paralysis of the respiratory muscles and by pinning the nerve to a recording platform. Single unit activity was isolated using principal component (PC) analysis and cluster cutting of data in multi-dimensional space (1-3 PCs). Cluster assignments were determined by a semi-automated approach using the k-means algorithm. The accuracy of single unit classification was assessed by checking inter-spike intervals (ISIs) to determine the length of the refractory period, and by cross-correlation analysis to assess whether single units were mistakenly split into more than one cluster. These analyses produced up to four isolated single units from each nerve filament (a bundle of nerve fibers), and typically it was possible to further increase yield by recording from several nerve filaments simultaneously using an array of electrodes. PMID:12573473

  12. Nerve biopsy

    MedlinePlus

    Nerve biopsy may be done to help diagnose: Axon degeneration (destruction of the axon portion of the nerve cell) Damage to the ... Demyelination Inflammation of the nerve Leprosy Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis

  13. Pinched Nerve

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Pinched Nerve Information Page Table of Contents (click to jump ... being done? Clinical Trials Organizations What is Pinched Nerve? The term "pinched nerve" is a colloquial term ...

  14. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation

    PubMed Central

    Patel, Yogi A.

    2015-01-01

    Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5–70 kHz and amplitudes of 0.1–3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function. PMID:25878155

  15. Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve

    PubMed Central

    Machhada, Asif; Ang, Richard; Ackland, Gareth L.; Ninkina, Natalia; Buchman, Vladimir L.; Lythgoe, Mark F.; Trapp, Stefan; Tinker, Andrew; Marina, Nephtali; Gourine, Alexander V.

    2015-01-01

    Background The central nervous origins of functional parasympathetic innervation of cardiac ventricles remain controversial. Objective This study aimed to identify a population of vagal preganglionic neurons that contribute to the control of ventricular excitability. An animal model of synuclein pathology relevant to Parkinson’s disease was used to determine whether age-related loss of the activity of the identified group of neurons is associated with changes in ventricular electrophysiology. Methods In vivo cardiac electrophysiology was performed in anesthetized rats in conditions of selective inhibition of the dorsal vagal motor nucleus (DVMN) neurons by pharmacogenetic approach and in mice with global genetic deletion of all family members of the synuclein protein. Results In rats anesthetized with urethane (in conditions of systemic beta-adrenoceptor blockade), muscarinic and neuronal nitric oxide synthase blockade confirmed the existence of a tonic parasympathetic control of cardiac excitability mediated by the actions of acetylcholine and nitric oxide. Acute DVMN silencing led to shortening of the ventricular effective refractory period (vERP), a lowering of the threshold for triggered ventricular tachycardia, and prolongation of the corrected QT (QTc) interval. Lower resting activity of the DVMN neurons in aging synuclein-deficient mice was found to be associated with vERP shortening and QTc interval prolongation. Conclusion Activity of the DVMN vagal preganglionic neurons is responsible for tonic parasympathetic control of ventricular excitability, likely to be mediated by nitric oxide. These findings provide the first insight into the central nervous substrate that underlies functional parasympathetic innervation of the ventricles and highlight its vulnerability in neurodegenerative diseases. PMID:26051529

  16. Low-level transcutaneous electrical vagus nerve stimulation suppresses atrial fibrillation

    PubMed Central

    Stavrakis, Stavros; Humphrey, Mary Beth; Scherlag, Benjamin J.; Hu, Yanqing; Jackman, Warren M.; Nakagawa, Hiroshi; Lockwood, Deborah; Lazzara, Ralph; Po, Sunny S.

    2015-01-01

    BACKGROUND Transcutaneous low-level tragus electrical stimulation (LLTS) suppresses atrial fibrillation (AF) in canines. OBJECTIVES We examined the antiarrhythmic and anti-inflammatory effects of LLTS in humans. METHODS Patients with paroxysmal AF who presented for AF ablation, were randomized to either 1 hour of LLTS (n = 20) or sham control (n = 20). Attaching a flat metal clip onto the tragus produced LLTS (20 Hz) in the right ear (50% lower than the voltage slowing the sinus rate). Under general anesthesia, AF was induced by burst atrial pacing at baseline and after 1 hour of LLTS or sham. Blood samples from the coronary sinus and the femoral vein were collected at those time points and then analyzed for inflammatory cytokines, including tumor necrosis factor (TNF)-α and C-reactive protein (CRP), using a multiplex immunoassay. RESULTS There were no differences in baseline characteristics between the 2 groups. Pacing-induced AF duration decreased significantly by 6.3 ± 1.9 min compared to baseline in the LLTS group, but not in the controls (p = 0.002 for comparison between groups). AF cycle length increased significantly from baseline by 28.8 ± 6.5 ms in the LLTS group, but not in controls (p = 0.0002 for comparison between groups). Systemic (femoral vein) but not coronary sinus TNF-α and CRP levels decreased significantly only in the LLTS group. CONCLUSIONS LLTS suppresses AF and decreases inflammatory cytokines in patients with paroxysmal AF. Our results support the emerging paradigm of neuromodulation to treat AF. PMID:25744003

  17. [Effect of narcotic analgesics on impulse conduction along the afferent pathways of visceral nerves].

    PubMed

    Churiukanov, V V; Sinitsyn, L N

    1976-06-01

    Experiments were conducted on chloralose-anesthetized cats. The action of morphine and promedol upon the potentials of the cortical and subcortical structures occurring after the visceral nerve stimulation was studied. Morphine proved to depress the potentials evoked by stimulation of the inferior cardiac and vagus nerves, in the specific, associative and nonspecific structures of the brain; promedol produced an analogous effect. Morphine also inhibited the potentials occurring after the stimulation of the splanchnic nerve in the associative and nonspecific structures; depression of the responses in the specific pathways was less pronounced. PMID:953307

  18. The Involvement of Parasympathetic and Sympathetic Nerve in the Inflammatory Reflex.

    PubMed

    Pereira, Mariana Rodrigues; Leite, Paulo Emílio Corrêa

    2016-09-01

    Production of inflammatory cytokines plays important roles in the response against tissue injury and in host defense. Alterations in the production of inflammatory cytokines may cause local or systemic inflammatory imbalance, culminating in organ failure or lethal systemic inflammation. The cholinergic anti-inflammatory pathway has been implicated as an important mechanism to regulate inflammation of targeted tissue. In this review, we discuss important advances, conflicting and controversial findings regarding the involvement of parasympathetic vagus and sympathetic splenic nerve through acetylcholine (ACh) release and α7 nicotinic acetylcholine receptor (nAChRα7) activation in the spleen. In addition, we address the involvement of cholinergic control of inflammation in other organs innerved by the vagus nerve such as gut, liver, kidney and lung, and independent of parasympathetic innervations such as skin and skeletal muscle. Then, other structures and mechanisms independent of vagus or splenic nerve may be involved in this process, such as local cells and motor neurons producing ACh. Altogether, the convergence of these findings may contribute to current anti-inflammatory strategies involving selective drug-targeting and electrical nerve stimulation. J. Cell. Physiol. 231: 1862-1869, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754950

  19. Nerve biopsy

    MedlinePlus

    ... Loss of axon tissue Metabolic neuropathies Necrotizing vasculitis Sarcoidosis Risks Allergic reaction to the local anesthetic Discomfort ... Neurosarcoidosis Peripheral neuropathy Primary amyloidosis Radial nerve dysfunction Sarcoidosis Tibial nerve dysfunction Update Date 6/1/2015 ...

  20. Nerve conduction

    MedlinePlus Videos and Cool Tools

    ... the spinal cord to muscles and sensory receptors. A peripheral nerve is composed of nerve bundles (fascicles) ... two neurons, it must first be converted to a chemical signal, which then crosses a space of ...

  1. Cranial nerve injuries with supraglottic airway devices: a systematic review of published case reports and series.

    PubMed

    Thiruvenkatarajan, V; Van Wijk, R M; Rajbhoj, A

    2015-03-01

    Cranial nerve injuries are unusual complications of supraglottic airway use. Branches of the trigeminal, glossopharyngeal, vagus and the hypoglossal nerve may all be injured. We performed a systematic review of published case reports and case series of cranial nerve injury from the use of supraglottic airway devices. Lingual nerve injury was the most commonly reported (22 patients), followed by recurrent laryngeal (17 patients), hypoglossal (11 patients), glossopharyngeal (three patients), inferior alveolar (two patients) and infra-orbital (one patient). Injury is generally thought to result from pressure neuropraxia. Contributing factors may include: an inappropriate size or misplacement of the device; patient position; overinflation of the device cuff; and poor technique. Injuries other than to the recurrent laryngeal nerve are usually mild and self-limiting. Understanding the diverse presentation of cranial nerve injuries helps to distinguish them from other complications and assists in their management. PMID:25376257

  2. In vitro receptor autoradiography reveals angiotensin IL (ANG II) binding associated with sensory and motor components of the vagus

    SciTech Connect

    Diz, D.I.; Barnes, K.L.; Ferrario, C.M.

    1986-03-05

    Specific, high affinity Ang II binding in the dog's dorsal medulla is concentrated in the area postrema, nucleus tractus solitarii (nTS) and dorsal motor nucleus of the vagus (dmnX). More recently Ang II binding sites were observed where bundles of vagal afferent fibers enter the dorsal medulla 6 mm rostral to obex and in the nodose ganglia and peripheral vagal nerves. Since Ang II binding in the nTS and dmnX overlies the distribution of vagal afferent fibers and efferent neurons, the effects of nodose ganglionectomy and cervical vagotomy on Ang II binding in the dorsal medulla were studied in rats and dogs using autoradiography after incubation of 14 ..mu..m coronal sections with 0.4 nM /sup 125/I-Ang II. Nonspecific binding was determined in the presence of 1 ..mu..m unlabeled Ang II. Two weeks after unilateral nodose ganglionectomy Ang II binding sites were absent ipsilaterally in the region where vagal afferent fibers enter the dorsal medulla. In the nTS and dmnX, binding near obex was reduced, while more rostrally these nuclei were almost completely devoid of Ang II binding on the denervated side. After cervical vagotomy, the loss of binding was restricted to the ipsilateral dmnX. These data are the first to reveal that Ang II binding in the dorsal medulla requires an intact vagal system.

  3. In vitro receptor autoradiography reveals angiotensin II (Ang II) binding associated with sensory and motor components of the vagus

    SciTech Connect

    Diz, D.I.; Barnes, K.L.; Ferrario, C.M.

    1986-03-05

    Specific, high affinity Ang II binding in the dog's dorsal medulla is concentrated in the area postrema, nucleus tractus solitarii (nTS) and dorsal motor nucleus of the vagus (dmnX). More recently Ang II binding sites were observed where bundles of vagal afferent fibers enter the dorsal medulla 6 mm rostral to obex and in the nodose ganglia and peripheral vagal nerves. Since Ang II binding in the nTS and dmnX overlies the distribution of vagal afferent fibers and efferent neurons, the effects of nodose ganglionectomy and cervical vagotomy on Ang II binding in the dorsal medulla were studied in rats and dogs using autoradiography after incubation of 14 ..mu..m coronal sections with 0.4 nM /sup 125/I-Ang II. Nonspecific binding was determined in the presence of 1 ..mu..M unlabeled Ang II. Two weeks after unilateral nodose ganglionectomy Ang II binding sites were absent ipsilaterally in the region where vagal afferent fibers enter the dorsal medulla. In the nTS and dmnX, binding near obex was reduced, while more rostrally these nuclei were almost completely devoid of Ang II binding on the denervated side. After cervical vagotomy, the loss of binding was restricted to the ipsilateral dmnX. These data are the first to reveal that Ang II binding in the dorsal medulla requires an intact vagal system.

  4. Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells.

    PubMed

    Costantini, Todd W; Bansal, Vishal; Krzyzaniak, Michael; Putnam, James G; Peterson, Carrie Y; Loomis, William H; Wolf, Paul; Baird, Andrew; Eliceiri, Brian P; Coimbra, Raul

    2010-12-01

    The enteric nervous system may have an important role in modulating gastrointestinal barrier response to disease through activation of enteric glia cells. In vitro studies have shown that enteric glia activation improves intestinal epithelial barrier function by altering the expression of tight junction proteins. We hypothesized that severe injury would increase expression of glial fibrillary acidic protein (GFAP), a marker of enteric glial activation. We also sought to define the effects of vagal nerve stimulation on enteric glia activation and intestinal barrier function using a model of systemic injury and local gut mucosal involvement. Mice with 30% total body surface area steam burn were used as model of severe injury. Vagal nerve stimulation was performed to assess the role of parasympathetic signaling on enteric glia activation. In vivo intestinal permeability was measured to assess barrier function. Intestine was collected to investigate changes in histology; GFAP expression was assessed by quantitative PCR, by confocal microscopy, and in GFAP-luciferase transgenic mice. Stimulation of the vagus nerve prevented injury-induced intestinal barrier injury. Intestinal GFAP expression increased at early time points following burn and returned to baseline by 24 h after injury. Vagal nerve stimulation prior to injury increased GFAP expression to a greater degree than burn alone. Gastrointestinal bioluminescence was imaged in GFAP-luciferase transgenic animals following either severe burn or vagal stimulation and confirmed the increased expression of intestinal GFAP. Injection of S-nitrosoglutathione, a signaling molecule released by activated enteric glia cells, following burn exerts protective effects similar to vagal nerve stimulation. Intestinal expression of GFAP increases following severe burn injury. Stimulation of the vagus nerve increases enteric glia activation, which is associated with improved intestinal barrier function. The vagus nerve may mediate the

  5. Histomorphogenesis of cranial nerves in Huso huso larvae.

    PubMed

    Tavighi, Sherma; Saadatfar, Zohreh; Shojaei, Bahador; Behnam Rassouli, Morteza

    2016-01-01

    In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed. PMID:27482355

  6. Histomorphogenesis of cranial nerves in Huso huso larvae

    PubMed Central

    Tavighi, Sherma; Saadatfar, Zohreh; Shojaei, Bahador; Behnam Rassouli, Morteza

    2016-01-01

    In this study the cranial nerves development of H. huso are explained from 1 to 54-days-old (1, 3, 6, 15, 21 and 54 days). Despite all the researches on fish brain, there are no study on nerves evolution on H. huso during their larvae life. For this research 40 samples of larvae H. huso were obtained (from each age, about six samples were selected). The specimens were maintained in fiberglass tank, then histological samples were taken from tissues and stained with hematoxylin and eosin for general histological studies using light microscope. According to the results, on 1 and 3-days-old, no nerve was observed. The terminal nerve and their dendrites were observed around the nasal cavity and the axons projected to different areas in forebrain especially around olfactory bulb diffusely, on 6-day-old fish. Also, olfactory, optic, oculomotor, trochlear, trigeminal, lateral line and vagus nerves were detected on 6-day-old fish, however two parts of lateral line nerve were separated on 54-day-old. Three nerves, profundus, facial and octaval were observed on 54-day-old, however, up to this age, epiphysial nerve was not observed. PMID:27482355

  7. Opioid Peptides Inhibit Excitatory But Not Inhibitory Synaptic Transmission in the Rat Dorsal Motor Nucleus of the Vagus

    PubMed Central

    Browning, Kirsteen N.; Kalyuzhny, Alexander E.; Travagli, R. Alberto

    2011-01-01

    Opioid peptides produce gastrointestinal inhibition and increase feeding when applied to the brainstem. The present studies were designed to determine the actions of opioid peptides on synaptic transmission within the dorsal motor nucleus of the vagus (DMV) and the localization of μ-opioid receptors. Whole-cell recordings were made from identified gastrointestinal-projecting DMV neurons in thin brainstem slices of the rat. Electrical stimulation of the nucleus of the tractus solitarius evoked EPSCs and IPSCs. In all neurons tested, methionine (Met)-enkephalin (0.003–30 μm) inhibited the peak amplitude of the EPSCs. The effect was prevented by naloxone (1 μm) as well as by naloxonazine (0.2 μm). An increase in the ratio of the evoked paired pulses indicated that the inhibition was attributable to actions at presynaptic receptors. This presynaptic inhibitory action was mimicked by [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (0.1 μm) and the analgesic dipeptide kyotorphin (10 μm) but not by cyclic[d-Pen2, d-Pen5]-enkephalin (1 μm) and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate (1 μm). In contrast, the amplitude of evoked IPSCs was not altered either by Met-enkephalin or by any of the opioid receptor-selective agonists. Immunohistochemical studies revealed that nerve terminals apposing DMV neurons showed immunoreactivity to μ-opioid receptors colocalized with glutamate immunoreactivity but not glutamic acid decarboxylase immunoreactivity. These results suggest that within the DMV, μ-opioid receptors are present on the nerve terminals of excitatory but not inhibitory inputs to GI motoneurons. Such specificity may imply that the central inhibitory action of opioid peptides on gastrointestinal function targets selected pathways. PMID:11943802

  8. A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy.

    PubMed

    Ward, Matthew P; Qing, Kurt Y; Otto, Kevin J; Worth, Robert M; John, Simon W M; Irazoqui, Pedro P

    2015-05-01

    Electrical vagus nerve stimulation is a treatment alternative for many epileptic and depressed patients whose symptoms are not well managed with pharmaceutical therapy. However, the fixed stimulus, open loop dosing mechanism limits its efficacy and precludes major advances in the quality of therapy. A real-time, responsive form of vagus nerve stimulation is needed to control nerve activation according to therapeutic need. This personalized approach to therapy will improve efficacy and reduce the number and severity of side effects. We present autonomous neural control, a responsive, biofeedback-driven approach that uses the degree of measured nerve activation to control stimulus delivery. We demonstrate autonomous neural control in rats, showing that it rapidly learns how to most efficiently activate any desired proportion of vagal A, B, and/or C fibers over time. This system will maximize efficacy by minimizing patient response variability and by minimizing therapeutic failures resulting from longitudinal decreases in nerve activation with increasing durations of treatment. The value of autonomous neural control equally applies to other applications of electrical nerve stimulation. PMID:25167554

  9. RGS Proteins in Heart: Brakes on the Vagus

    PubMed Central

    Stewart, Adele; Huang, Jie; Fisher, Rory A.

    2012-01-01

    It has been nearly a century since Otto Loewi discovered that acetylcholine (ACh) release from the vagus produces bradycardia and reduced cardiac contractility. It is now known that parasympathetic control of the heart is mediated by ACh stimulation of Gi/o-coupled muscarinic M2 receptors, which directly activate G protein-coupled inwardly rectifying potassium (GIRK) channels via Gβγ resulting in membrane hyperpolarization and inhibition of action potential (AP) firing. However, expression of M2R–GIRK signaling components in heterologous systems failed to recapitulate native channel gating kinetics. The missing link was identified with the discovery of regulator of G protein signaling (RGS) proteins, which act as GTPase-activating proteins to accelerate the intrinsic GTPase activity of Gα resulting in termination of Gα- and Gβγ-mediated signaling to downstream effectors. Studies in mice expressing an RGS-insensitive Gαi2 mutant (G184S) implicated endogenous RGS proteins as key regulators of parasympathetic signaling in heart. Recently, two RGS proteins have been identified as critical regulators of M2R signaling in heart. RGS6 exhibits a uniquely robust expression in heart, especially in sinoatrial (SAN) and atrioventricular nodal regions. Mice lacking RGS6 exhibit increased bradycardia and inhibition of SAN AP firing in response to CCh as well as a loss of rapid activation and deactivation kinetics and current desensitization for ACh-induced GIRK current (IKACh). Similar findings were observed in mice lacking RGS4. Thus, dysregulation in RGS protein expression or function may contribute to pathologies involving aberrant electrical activity in cardiac pacemaker cells. Moreover, RGS6 expression was found to be up-regulated in heart under certain pathological conditions, including doxorubicin treatment, which is known to cause life-threatening cardiotoxicity and atrial fibrillation in cancer patients. On the other hand, increased vagal tone may be

  10. Morphologic Characterization of Nerves in Whole-Mount Airway Biopsies

    PubMed Central

    Canning, Brendan J.; Merlo-Pich, Emilio; Woodcock, Ashley A.; Smith, Jaclyn A.

    2015-01-01

    Rationale: Neuroplasticity of bronchopulmonary afferent neurons that respond to mechanical and chemical stimuli may sensitize the cough reflex. Afferent drive in cough is carried by the vagus nerve, and vagal afferent nerve terminals have been well defined in animals. Yet, both unmyelinated C fibers and particularly the morphologically distinct, myelinated, nodose-derived mechanoreceptors described in animals are poorly characterized in humans. To date there are no distinctive molecular markers or detailed morphologies available for human bronchopulmonary afferent nerves. Objectives: Morphologic and neuromolecular characterization of the afferent nerves that are potentially involved in cough in humans. Methods: A whole-mount immunofluorescence approach, rarely used in human lung tissue, was used with antibodies specific to protein gene product 9.5 (PGP9.5) and, for the first time in human lung tissue, 200-kD neurofilament subunit. Measurements and Main Results: We have developed a robust technique to visualize fibers consistent with autonomic and C fibers and pulmonary neuroendocrine cells. A group of morphologically distinct, 200-kD neurofilament-immunopositive myelinated afferent fibers, a subpopulation of which did not express PGP9.5, was also identified. Conclusions: PGP9.5-immunonegative nerves are strikingly similar to myelinated airway afferents, the cough receptor, and smooth muscle–associated airway receptors described in rodents. These have never been described in humans. Full description of human airway nerves is critical to the translation of animal studies to the clinical setting. PMID:25906337

  11. Recurrent largngeal nerve paralysis: a laryngographic and computed tomographic study

    SciTech Connect

    Agha, F.P.

    1983-07-01

    Vocal cord paralysis is a relatively common entity, usually resulting from a pathologic process of the vagus nerve or its recurrent larynegeal branch. It is rarely caused by intralargngeal lesions. Four teen patients with recurrent laryngeal nerve paralysis (RLNP) were evaluated by laryngography, computed tomography (CT), or both. In the evaluation of the paramedian cord, CT was limited in its ability to differentiate between tumor or RLNP as the cause of the fixed cord, but it yielded more information than laryngography on the structural abnormalities of the larynx and pre-epiglottic and paralaryngeal spaces. Laryngography revealed distinct features of RLNP and is the procedure of choice for evaluation of functional abnormalities of the larynx until further experience with faster CT scanners and dynamic scanning of the larynx is gained.

  12. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  13. Optic nerve atrophy

    MedlinePlus

    Optic nerve atrophy is damage to the optic nerve. The optic nerve carries images of what the eye sees to ... problem most often affects older adults. The optic nerve can also be damaged by shock, toxins, radiation, ...

  14. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  15. Nerve biopsy (image)

    MedlinePlus

    Nerve biopsy is the removal of a small piece of nerve for examination. Through a small incision, a sample ... is removed and examined under a microscope. Nerve biopsy may be performed to identify nerve degeneration, identify ...

  16. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  17. Role of the Esophageal Vagus Neural Pathway in Ionizing Irradiation-induced Seizures in Nitric Oxide Synthase-1 Homologous Recombinant Negative NOS1−/− Mice

    PubMed Central

    BERNARD, MARK E.; KIM, HYUN; RWIGEMA, JEAN-CLAUDE; EPPERLY, MICHAEL W.; KELLEY, ERIC E.; MURDOCH, GEOFFERY H.; DIXON, TRACY; WANG, HONG; GREENBERGER, JOEL S.

    2012-01-01

    Aim We sought to define the mechanism of total body irradiation (TBI)-induced seizures in NOS1−/− mice and amelioration by intra-esophageal manganese superoxide dismutase-plasmid liposomes (MnSOD-PL). Materials and Methods We evaluated the role of vagus nerve pathways in irradiation-induced seizures using biochemical, physiologic, and histopathologic techniques. Results Heterozygous NOS1+/− mice demonstrated radioresistance similar to wild-type C57BL/6NHsd mice (p=0.9269). Irradiation-induced lipid peroxidation in fetal brain cultures from NOS1−/− or wild-type mice was reduced by MnSOD-PL. Right-sided vagotomy did not alter the TBI radiation response of wild-type or reverse the radiosensitivity of NOS1−/− mice. Excised esophagus from irradiated NOS1−/− mice demonstrated an increased histopathologic inflammatory response compared to C57BL/6NHsd mice. Conclusion NOS1−/− mice represent a model system for dissecting the developmental abnormalities leading to esophageal-mediated TBI-induced seizures. PMID:22021678

  18. Localization of the cricothyroid muscle under ultrasound guidance for vagal nerve mapping.

    PubMed

    Yang, Tsui-Fen; Wang, Jia-Chi; Hsu, Sanford P C; Lee, Cheng-Chia; Lin, Chun-Fu; Chiu, Jan-Wei; Lai, Chih-Jou; Chan, Rai-Chi; Lee, Shinn-Shing

    2015-05-01

    During surgical removal of tumors of the skull base or cerebellopontine angle with brainstem compression, the vagus nerve is at a high risk for injury that can result in permanent or transient swallowing and speech dysfunction. Intramuscular recording of cricothyroid muscle can be used for vagal nerve mapping during intraoperative neurophysiologic monitoring so as to prevent the above complications. However, it is a small muscle that lies beneath the strap muscles over the anterior neck and is not easily accessible by a blind approach. Here, we present a case in which cricothyroid muscle was identified for precise electrode placement under ultrasound guidance during preparation for intraoperative monitoring. We concluded that localization of the cricothyroid muscle by ultrasonography proved to be a feasible and easy technique, and the compound muscle action potential recorded by this approach is clearly recognizable during intraoperative vagal nerve mapping. PMID:25681020

  19. Evaluation of Insecticides Susceptibility and Malaria Vector Potential of Anopheles annularis s.l. and Anopheles vagus in Assam, India

    PubMed Central

    Dhiman, Sunil; Yadav, Kavita; Rabha, Bipul; Goswami, Diganta; Hazarika, S.; Tyagi, Varun

    2016-01-01

    During the recent past, development of DDT resistance and reduction to pyrethroid susceptibility among the malaria vectors has posed a serious challenge in many Southeast Asian countries including India. Current study presents the insecticide susceptibility and knock-down data of field collected Anopheles annularis sensu lato and An. vagus mosquito species from endemic areas of Assam in northeast India. Anopheles annularis s.l. and An. vagus adult females were collected from four randomly selected sentinel sites in Orang primary health centre (OPHC) and Balipara primary health centre (BPHC) areas, and used for testing susceptibility to DDT, malathion, deltamethrin and lambda-cyhalothrin. After insecticide susceptibility tests, mosquitoes were subjected to VectorTest™ assay kits to detect the presence of malaria sporozoite in the mosquitoes. An. annularis s.l. was completely susceptible to deltamethrin, lambda-cyhalothrin and malathion in both the study areas. An. vagus was highly susceptible to deltamethrin in both the areas, but exhibited reduced susceptibility to lambda-cyhalothrin in BPHC. Both the species were resistant to DDT and showed very high KDT50 and KDT99 values for DDT. Probit model used to calculate the KDT50 and KDT99 values did not display normal distribution of percent knock-down with time for malathion in both the mosquito species in OPHC (p<0.05) and An. vagus in BPHC (χ2 = 25.3; p = 0.0), and also for deltamethrin to An. vagus in BPHC area (χ2 = 15.4; p = 0.004). Minimum infection rate (MIR) of Plasmodium sporozoite for An. vagus was 0.56 in OPHC and 0.13 in BPHC, while for An. annularis MIR was found to be 0.22 in OPHC. Resistance management strategies should be identified to delay the expansion of resistance. Testing of field caught Anopheles vectors from different endemic areas for the presence of malaria sporozoite may be useful to ensure their role in malaria transmission. PMID:27010649

  20. Evaluation of Insecticides Susceptibility and Malaria Vector Potential of Anopheles annularis s.l. and Anopheles vagus in Assam, India.

    PubMed

    Dhiman, Sunil; Yadav, Kavita; Rabha, Bipul; Goswami, Diganta; Hazarika, S; Tyagi, Varun

    2016-01-01

    During the recent past, development of DDT resistance and reduction to pyrethroid susceptibility among the malaria vectors has posed a serious challenge in many Southeast Asian countries including India. Current study presents the insecticide susceptibility and knock-down data of field collected Anopheles annularis sensu lato and An. vagus mosquito species from endemic areas of Assam in northeast India. Anopheles annularis s.l. and An. vagus adult females were collected from four randomly selected sentinel sites in Orang primary health centre (OPHC) and Balipara primary health centre (BPHC) areas, and used for testing susceptibility to DDT, malathion, deltamethrin and lambda-cyhalothrin. After insecticide susceptibility tests, mosquitoes were subjected to VectorTest™ assay kits to detect the presence of malaria sporozoite in the mosquitoes. An. annularis s.l. was completely susceptible to deltamethrin, lambda-cyhalothrin and malathion in both the study areas. An. vagus was highly susceptible to deltamethrin in both the areas, but exhibited reduced susceptibility to lambda-cyhalothrin in BPHC. Both the species were resistant to DDT and showed very high KDT50 and KDT99 values for DDT. Probit model used to calculate the KDT50 and KDT99 values did not display normal distribution of percent knock-down with time for malathion in both the mosquito species in OPHC (p<0.05) and An. vagus in BPHC (χ2 = 25.3; p = 0.0), and also for deltamethrin to An. vagus in BPHC area (χ2 = 15.4; p = 0.004). Minimum infection rate (MIR) of Plasmodium sporozoite for An. vagus was 0.56 in OPHC and 0.13 in BPHC, while for An. annularis MIR was found to be 0.22 in OPHC. Resistance management strategies should be identified to delay the expansion of resistance. Testing of field caught Anopheles vectors from different endemic areas for the presence of malaria sporozoite may be useful to ensure their role in malaria transmission. PMID:27010649

  1. Morphologic pattern of the intrinsic ganglionated nerve plexus in the mouse heart

    PubMed Central

    Rysevaite, Kristina; Saburkina, Inga; Pauziene, Neringa; Noujaim, Sami; Jalife, José; Pauza, Dainius H.

    2011-01-01

    Summary BACKGROUND Both normal and genetically modified mice are excellent models to investigate molecular mechanisms of arrhythmogenic cardiac diseases that may associate with an imbalance between the sympathetic and the parasympathetic nervous input to the heart. OBJECTIVE We sought to: (1) determine the structural organization of the mouse cardiac neural plexus; (2) identify extrinsic neural sources and their relationship with the cardiac plexus; and (3) reveal any anatomical differences in the cardiac plexus between mouse and other species. METHODS Cardiac nerve structures were visualized employing histochemical staining for acetylcholinesterase (AChE) on whole heart and thorax-dissected preparations derived from 25 mice. To confirm reliability of staining parasympathetic and sympathetic neural components in the mouse heart we applied a histochemical method for AChE and imunohistochemistry for tyrosine hydroxylase (TH) and/or choline acetyltransferase (ChAT) on whole mounts preparations from 6 mice. RESULTS The double immunohistochemical labeling of TH and ChAT on AChE positive neural elements in mouse whole mounts demonstrated equal staining of nerves and ganglia for AChE that were positive for both TH and ChAT. The extrinsic cardiac nerves access the mouse heart at the right (RCV) and left (LCV) cranial veins and interblend within the ganglionated nerve plexus of the heart hilum that is persistently localized on the heart base. Nerves and bundles of nerve fibers extend epicardially from this plexus to atria and ventricles by left dorsal, dorsal right atrial, right ventral, and ventral left atrial routes or subplexuses. The RCV received extrinsic nerves mainly originated from the right cervicothoracic ganglion and a branch of the right vagus nerve, while the LCV was supplied by extrinsic nerves from the left cervicothoracic ganglion and the left vagus nerve. The majority of intrinsic cardiac ganglia were localized on the heart base at the roots of pulmonary

  2. Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A

    PubMed Central

    YI, CHUNFENG; ZHANG, CHANGJIANG; HU, XIAORONG; LI, YUANHONG; JIANG, HONG; XU, WEIPAN; LU, JIAJIA; LIAO, YUANXI; MA, RUISONG; LI, XUEFEI; WANG, JICHUN

    2016-01-01

    Interleukin (IL)-17A has an important role in myocardial ischemia/reperfusion (I/R) injury, and vagal stimulation (VS) has been demonstrated to exert cardioprotective effects. The present study aimed to investigate the effects of VS on a rat model of myocardial I/R injury, and detected an association between VS and IL-17A. Anesthetized rats underwent VS (2 msec; 10 Hz) or were treated with anti-IL-17A neutralized monoclonal antibodies (mAbs) (200 µg; iv), and subjected to ischemia for 30 min prior to 4 h reperfusion. The following parameters were measured: Infarct size; lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity levels; tumor necrosis factor (TNF)-α and IL-6 expression levels; and the percentage of terminal deoxynucleotidyl-transferase mediated dUTP nick-end labeling (TUNEL) positive cells. High mobility group box 1 protein (HMGB1) and IL-17A expression levels were assessed by immunoblotting. Following 4 h reperfusion, VS was able to significantly decrease the infarct size and the activity levels of LDH and CK (P<0.05). Furthermore, VS administration significantly suppressed the increased MDA and decreased SOD activity levels, and significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells (P<0.05). Treatment with anti-IL-17A mAbs demonstrated the same effects as VS. Furthermore, VS was able to significantly inhibit the increased expression levels of TNF-α, IL-6, HMGB1 and IL-17A induced by I/R (P<0.05). The results of the present study suggested that VS may attenuate myocardial I/R injury by reducing the expression of inflammatory cytokines, oxidative stress and the apoptosis of cardiomyocytes. Furthermore, VS may induce cardioprotective effects, which may be associated with the inhibition of IL-17A expression. PMID:26889235

  3. Electrochemical and Electrophysiological Performance of Platinum Electrodes Within the Ninety-Nine-Electrode Stimulating Nerve Cuff.

    PubMed

    Pečlin, Polona; Mehle, Andraž; Karpe, Blaž; Rozman, Janez

    2015-10-01

    The trend in neural prostheses using selective nerve stimulation for electrical stimulation therapies is headed toward single-part systems having a large number of working electrodes (WEs), each of which selectively stimulate neural tissue or record neural response (NR). The present article reviews the electrochemical and electrophysiological performance of platinum WE within a ninety-nine-electrode spiral cuff for selective nerve stimulation and recording of peripheral nerves, with a focus on the vagus nerve (VN). The electrochemical properties of the WE were studied in vitro using the electrochemical impedance spectroscopy (EIS) technique. The equivalent circuit model (ECM) of the interface between the WE and neural tissue was extracted from the EIS data and simulated in the time domain using a preset current stimulus. Electrophysiological performance of in-space and fiber-type highly selective vagus nerve stimulation (VNS) was tested using an isolated segment of a porcine VN and carotid artery as a reference. A quasitrapezoidal current-controlled pulse (stimulus) was applied to the VN or arterial segment using an appointed group of three electrodes (triplet). The triplet and stimulus were configured to predominantly stimulate B-fibers and minimize the stimulation of A-fibers. The EIS results revealed capacitive charge transfer predominance, which is a highly desirable property. Electrophysiological performance testing indicated the potential existence of certain parameters and waveforms of the stimulus for which the contribution of the A-fibers to the NR decreased slightly and that of the B-fibers increased slightly. Findings show that the design of the stimulating electrodes, based on the EIS and ECM results, could act as a useful tool for nerve cuff development. PMID:26471140

  4. Nerve conduction velocity

    MedlinePlus

    Nerve conduction velocity (NCV) is a test to see how fast electrical signals move through a nerve. ... normal body temperature. Being too cold slows nerve conduction. Tell your doctor if you have a cardiac ...

  5. Femoral nerve damage (image)

    MedlinePlus

    The femoral nerve is located in the leg and supplies the muscles that assist help straighten the leg. It supplies sensation ... leg. One risk of damage to the femoral nerve is pelvic fracture. Symptoms of femoral nerve damage ...

  6. Ulnar nerve damage (image)

    MedlinePlus

    The ulnar nerve originates from the brachial plexus and travels down arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near the surface of the body where ...

  7. Diabetes and nerve damage

    MedlinePlus

    ... hot or cold When the nerves that control digestion are affected, you may have trouble digesting food. ... harder to control. Damage to nerves that control digestion almost always occurs in people with severe nerve ...

  8. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... or past infection, or immunity to hepatitis A Hepatitis B tests: Hepatitis B surface antigen (HBsAg), you have ...

  9. Hepatitis C and HIV

    MedlinePlus

    ... Problems : Hepatitis C Subscribe Translate Text Size Print Hepatitis C What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis B . Hepatitis C and HIV About 25% of people living ...

  10. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  11. Hepatitis Testing

    MedlinePlus

    ... caused by viruses. They include hepatitis A, hepatitis B, and hepatitis C. To diagnose hepatitis, your health care provider will ask you about your medical history and symptoms, do a physical exam, and order blood tests. There are blood tests for each type of ...

  12. Hepatitis B and Hepatitis C in Pregnancy

    MedlinePlus

    ... infected with the hepatitis B virus, can I breastfeed? • If I am infected with the hepatitis B ... infected with the hepatitis C virus, can I breastfeed? • Glossary What are hepatitis B and hepatitis C ...

  13. Hepatitis virus panel

    MedlinePlus

    Hepatitis A antibody test; Hepatitis B antibody test; Hepatitis C antibody test; Hepatitis D antibody test ... There are different tests for hepatitis A and B. A positive test is ... may mean: You currently have a hepatitis infection. This may ...

  14. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  15. Hepatitis C and Incarceration

    MedlinePlus

    HEPATITIS C & INCARCERATION What is hepatitis? “Hepatitis” means inflammation or swelling of the liver. The liver is an important ... viral hepatitis: Hepatitis A, Hepatitis B, and Hepatitis C. They are all different from each other and ...

  16. Hepatic Encephalopathy

    MedlinePlus Videos and Cool Tools

    ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ... medical care is an important factor in staying as healthy as possible. The American Liver Foundation is ...

  17. Hepatitis D

    MedlinePlus

    ... if the hepatitis B virus is also present. Transmission Hepatitis D can be found in the blood, ... other body fluids of people who are infected. Transmission happens when infected body fluid enters another person’s ...

  18. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  19. Hepatic ischemia

    MedlinePlus

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  20. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  1. Hepatitis B

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

  2. Hepatitis C

    MedlinePlus

    ... 2014 Select a Language: Fact Sheet 507 Hepatitis C WHAT IS HEPATITIS C? HOW IS IT DIAGNOSED? ... treatment may be less likely to work. Hep C treatment is less effective for coinfected people. Cure ...

  3. Hepatitis A

    MedlinePlus

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  4. Hepatitis A

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Español Hepatitis A Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is hepatitis A? Hepatitis * A is a virus , or infection, ...

  5. Autoimmune Hepatitis

    MedlinePlus

    ... Organizations ​​ (PDF, 341 KB)​​​​​ Alternate Language URL Autoimmune Hepatitis Page Content On this page: What is autoimmune ... Points to Remember Clinical Trials What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ...

  6. Hepatitis C

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  7. Nerve conduction velocity

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003927.htm Nerve conduction velocity To use the sharing features on this page, please enable JavaScript. Nerve conduction velocity (NCV) is a test to see how ...

  8. Assessing nerves in leprosy.

    PubMed

    Garbino, José Antonio; Heise, Carlos Otto; Marques, Wilson

    2016-01-01

    Leprosy neuropathy is dependent on the patient's immune response and expresses itself as a focal or multifocal neuropathy with asymmetric involvement. Leprosy neuropathy evolves chronically but recurrently develops periods of exacerbation during type 1 or type 2 reactions, leading to acute neuropathy. Nerve enlargement leading to entrapment syndromes is also a common manifestation. Pain may be either of inflammatory or neuropathic origin. A thorough and detailed evaluation is mandatory for adequate patient follow-up, including nerve palpation, pain assessment, graded sensory mapping, muscle power testing, and autonomic evaluation. Nerve conduction studies are a sensitive tool for nerve dysfunction, including new lesions during reaction periods or development of entrapment syndromes. Nerve ultrasonography is also a very promising method for nerve evaluation in leprosy. The authors propose a composite nerve clinical score for nerve function assessment that can be useful for longitudinal evaluation. PMID:26773623

  9. Electromechanical Nerve Stimulator

    NASA Technical Reports Server (NTRS)

    Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

    1993-01-01

    Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

  10. Ulnar nerve damage (image)

    MedlinePlus

    ... arm. The nerve is commonly injured at the elbow because of elbow fracture or dislocation. The ulnar nerve is near ... surface of the body where it crosses the elbow, so prolonged pressure on the elbow or entrapment ...

  11. Nerve Injuries in Athletes.

    ERIC Educational Resources Information Center

    Collins, Kathryn; And Others

    1988-01-01

    Over a two-year period this study evaluated the condition of 65 athletes with nerve injuries. These injuries represent the spectrum of nerve injuries likely to be encountered in sports medicine clinics. (Author/MT)

  12. Radial nerve dysfunction (image)

    MedlinePlus

    The radial nerve travels down the arm and supplies movement to the triceps muscle at the back of the upper arm. ... the wrist and hand. The usual causes of nerve dysfunction are direct trauma, prolonged pressure on the ...

  13. Tibial nerve dysfunction

    MedlinePlus

    ... a loss of movement or sensation in the foot from damage to the tibial nerve. ... Tibial nerve dysfunction is an unusual form of peripheral ... the calf and foot muscles. A problem in function with a single ...

  14. Degenerative Nerve Diseases

    MedlinePlus

    Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...

  15. Radial nerve dysfunction

    MedlinePlus

    ... nerve leads to problems with movement in the arm and wrist and with sensation in the back of the arm or hand. ... to the radial nerve, which travels down the arm and controls movement of the triceps muscle at ...

  16. Laryngeal nerve damage

    MedlinePlus

    Laryngeal nerve damage is injury to one or both of the nerves that are attached to the voice box. ... Injury to the laryngeal nerves is uncommon. When it does occur, it can be from: A complication of neck or chest surgery (especially thyroid, lung, ...

  17. Neurological Complications in Thyroid Surgery: A Surgical Point of View on Laryngeal Nerves

    PubMed Central

    Varaldo, Emanuela; Ansaldo, Gian Luca; Mascherini, Matteo; Cafiero, Ferdinando; Minuto, Michele N.

    2014-01-01

    The cervical branches of the vagus nerve that are pertinent to endocrine surgery are the superior and the inferior laryngeal nerves: their anatomical course in the neck places them at risk during thyroid surgery. The external branch of the superior laryngeal nerve (EB) is at risk during thyroid surgery because of its close anatomical relationship with the superior thyroid vessels and the superior thyroid pole region. The rate of EB injury (which leads to the paralysis of the cricothyroid muscle) varies from 0 to 58%. The identification of the EB during surgery helps avoiding both an accidental transection and an excessive stretching. When the nerve is not identified, the ligation of superior thyroid artery branches close to the thyroid gland is suggested, as well as the abstention from an indiscriminate use of energy-based devices that might damage it. The inferior laryngeal nerve (RLN) runs in the tracheoesophageal groove toward the larynx, close to the posterior aspect of the thyroid. It is the main motor nerve of the intrinsic laryngeal muscles, and also provides sensory innervation to the larynx. Its injury finally causes the paralysis of the omolateral vocal cord and various sensory alterations: the symptoms range from mild to severe hoarseness, to acute airway obstruction, and swallowing impairment. Permanent lesions of the RNL occur from 0.3 to 7% of cases, according to different factors. The surgeon must be aware of the possible anatomical variations of the nerve, which should be actively searched for and identified. Visual control and gentle dissection of RLN are imperative. The use of intraoperative nerve monitoring has been safely applied but, at the moment, its impact in the incidence of RLN injuries has not been clarified. In conclusion, despite a thorough surgical technique and the use of intraoperative neuromonitoring, the incidence of neurological complications after thyroid surgery cannot be suppressed, but should be maintained in a low range. PMID

  18. Tonic GABAA Receptor-Mediated Inhibition in the Rat Dorsal Motor Nucleus of the Vagus

    PubMed Central

    Gao, Hong

    2010-01-01

    Type A γ-aminobutyric acid (GABAA) receptors expressed in the dorsal motor nucleus of vagus (DMV) critically regulate the activity of vagal motor neurons and, by inference, the gastrointestinal (GI) tract. Two types of GABAA receptor-mediated inhibition have been identified in the brain, represented by phasic (Iphasic) and tonic (Itonic) inhibitory currents. The hypothesis that Itonic regulates neuron activity was tested in the DMV using whole cell patch-clamp recordings in transverse brain stem slices from rats. An Itonic was present in a subset of DMV neurons, which was determined to be mediated by different receptors than those mediating fast, synaptic currents. Preapplication of tetrodotoxin significantly decreased the resting Itonic amplitude in DMV neurons, suggesting that most of the current was due to action potential (AP)–dependent GABA release. Blocking GABA transport enhanced Itonic and multiple GABA transporters cooperated to regulate Itonic. The Itonic was composed of both a gabazine-insensitive component that was nearly saturated under basal conditions and a gabazine-sensitive component that was activated when extracellular GABA concentration was elevated. Perfusion of THIP (10 μM) significantly increased Itonic amplitude without increasing Iphasic amplitude. The Itonic played a major role in determining the overall excitability of DMV neurons by contributing to resting membrane potential and AP frequency. Our results indicate that Itonic contributes to DMV neuron membrane potential and activity and is thus an important regulator of vagally mediated GI function. PMID:20018836

  19. Hepatitis Vaccines.

    PubMed

    Ogholikhan, Sina; Schwarz, Kathleen B

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  20. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  1. High Median Nerve Injuries.

    PubMed

    Isaacs, Jonathan; Ugwu-Oju, Obinna

    2016-08-01

    The median nerve serves a crucial role in extrinsic and intrinsic motor and sensory function to the radial half of the hand. High median nerve injuries, defined as injuries proximal to the anterior interosseous nerve origin, therefore typically result in significant functional loss prompting aggressive surgical management. Even with appropriate recognition and contemporary nerve reconstruction, however, motor and sensory recovery may be inadequate. With isolated persistent high median nerve palsies, a variety of available tendon transfers can improve key motor functions and salvage acceptable use of the hand. PMID:27387077

  2. [Ganglia of peripheral nerves].

    PubMed

    Tatagiba, M; Penkert, G; Samii, M

    1993-01-01

    The authors present two different types of ganglion affecting the peripheral nerves: extraneural and intraneural ganglion. Compression of peripheral nerves by articular ganglions is well known. The surgical management involves the complete removal of the lesion with preservation of most nerve fascicles. Intraneural ganglion is an uncommon lesion which affects the nerve diffusely. The nerve fascicles are usually intimately involved between the cysts, making complete removal of all cysts impossible. There is no agreement about the best surgical management to be applied in these cases. Two possibilities are available: opening of the epineural sheath lengthwise and pressing out the lesion; or resection of the affected part of the nerve and performing a nerve reconstruction. While in case of extraneural ganglion the postoperative clinical evolution is very favourable, only long follow up studies will reveal in case of intraneural ganglion the best surgical approach. PMID:8128785

  3. Assessment of nerve morphology in nerve activation during electrical stimulation

    NASA Astrophysics Data System (ADS)

    Gomez-Tames, Jose; Yu, Wenwei

    2013-10-01

    The distance between nerve and stimulation electrode is fundamental for nerve activation in Transcutaneous Electrical Stimulation (TES). However, it is not clear the need to have an approximate representation of the morphology of peripheral nerves in simulation models and its influence in the nerve activation. In this work, depth and curvature of a nerve are investigated around the middle thigh. As preliminary result, the curvature of the nerve helps to reduce the simulation amplitude necessary for nerve activation from far field stimulation.

  4. Hepatitis B Vaccine

    MedlinePlus

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  5. Hepatitis A Vaccine

    MedlinePlus

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  6. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  7. Autoimmune hepatitis

    MedlinePlus

    ... diseases. These include: Graves disease Inflammatory bowel disease Rheumatoid arthritis Scleroderma Sjogren syndrome Systemic lupus erythematosus Thyroiditis Type 1 diabetes Ulcerative colitis Autoimmune hepatitis may occur in family ...

  8. Hepatitis B

    MedlinePlus

    ... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...

  9. Neural Mechanisms That Underlie Angina-Induced Referred Pain in the Trigeminal Nerve Territory: A c-Fos Study in Rats

    PubMed Central

    Hayashi, Bunsho; Maeda, Masako; Inoue, Tomio

    2013-01-01

    The present study was designed to determine whether the trigeminal sensory nuclear complex (TSNC) is involved in angina-induced referred pain in the trigeminal nerve territory and to identify the peripheral nerve conducting nociceptive signals that are input into the TSNC. Following application of the pain producing substance (PPS) infusion, the number of Fos-labeled cells increased significantly in the subnucleus caudalis (Sp5C) compared with other nuclei in the TSNC. The Fos-labeled cells in the Sp5C disappeared when the left and right cervical vagus nerves were sectioned. Lesion of the C1-C2 spinal segments did not reduce the number of Fos-labeled cells. These results suggest that the nociceptive signals that conduct vagal afferent fibers from the cardiac region are input into the Sp5C and then projected to the thalamus. PMID:27335881

  10. The Furcal Nerve Revisited

    PubMed Central

    Dabke, Harshad V.

    2014-01-01

    Atypical sciatica and discrepancy between clinical presentation and imaging findings is a dilemma for treating surgeon in management of lumbar disc herniation. It also constitutes ground for failed back surgery and potential litigations thereof. Furcal nerve (Furcal = forked) is an independent nerve with its own ventral and dorsal branches (rootlets) and forms a link nerve that connects lumbar and sacral plexus. Its fibers branch out to be part of femoral and obturator nerves in-addition to the lumbosacral trunk. It is most commonly found at L4 level and is the most common cause of atypical presentation of radiculopathy/sciatica. Very little is published about the furcal nerve and many are unaware of its existence. This article summarizes all the existing evidence about furcal nerve in English literature in an attempt to create awareness and offer insight about this unique entity to fellow colleagues/professionals involved in spine care. PMID:25317309