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1.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652990

RESUMO

Ischemic stroke is a worldwide major cause of mortality and disability and has high costs in terms of health-related quality of life and expectancy as well as of social healthcare resources. In recent years, starting from the bidirectional relationship between autonomic nervous system (ANS) dysfunction and acute ischemic stroke (AIS), researchers have identified prognostic factors for risk stratification, prognosis of mid-term outcomes and response to recanalization therapy. In particular, the evaluation of the ANS function through the analysis of heart rate variability (HRV) appears to be a promising non-invasive and reliable tool for the management of patients with AIS. Furthermore, preclinical molecular studies on the pathophysiological mechanisms underlying the onset and progression of stroke damage have shown an extensive overlap with the activity of the vagus nerve. Evidence from the application of vagus nerve stimulation (VNS) on animal models of AIS and on patients with chronic ischemic stroke has highlighted the surprising therapeutic possibilities of neuromodulation. Preclinical molecular studies highlighted that the neuroprotective action of VNS results from anti-inflammatory, antioxidant and antiapoptotic mechanisms mediated by α7 nicotinic acetylcholine receptor. Given the proven safety of non-invasive VNS in the subacute phase, the ease of its use and its possible beneficial effect in hemorrhagic stroke as well, human studies with transcutaneous VNS should be less challenging than protocols that involve invasive VNS and could be the proof of concept that neuromodulation represents the very first therapeutic approach in the ultra-early management of stroke.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , /terapia , Estimulação do Nervo Vago , Animais , Humanos , Fatores de Risco , Resultado do Tratamento , Estimulação do Nervo Vago/métodos
2.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760191

RESUMO

The present study investigated the role of electrical stimulation of the vagus nerve in the acute lung injury (ALI) inflammatory response induced by lipopolysaccharide (LPS) in rats. A rat model of ALI was established using LPS and by connecting an electrode to the left vagus nerve proximal to the heart in order to provide continuous electrical stimulation (1 mA; 1 msec; 10 Hz). After 120 min, the rat lung tissue was stained with hematoxylin and eosin and the expression of inflammatory factors was evaluated by reverse transcription­quantitative PCR and western blot analysis. The change in apoptosis rate in cells from bronchoalveolar lavage fluid (BALF) was analyzed using flow cytometry. The results of the present study demonstrated that inflammatory cell infiltration, alveolar wall and interstitial thickening, and lung hyperemia in rats with LPS­induced ALI were decreased following electrical stimulation of the vagus nerve. Electrical stimulation inhibited the expression levels of IL­1, IL­6, IL­10, IL-8 and TNF­α at both the mRNA and protein levels and decreased early and late apoptosis rates in inflammatory cells from BALF. The results indicated that vagus nerve stimulation can reverse the inflammatory response in lung injury, thereby exerting a pulmonary protective effect.


Assuntos
Lesão Pulmonar Aguda/terapia , Estimulação Elétrica , Coração/inervação , Nervo Vago/efeitos da radiação , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar , Regulação da Expressão Gênica/efeitos da radiação , Coração/fisiopatologia , Coração/efeitos da radiação , Humanos , Interleucina-10/genética , Interleucina-6/genética , Interleucina-8/genética , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos da radiação , Ratos , Fator de Necrose Tumoral alfa/genética , Nervo Vago/patologia , Estimulação do Nervo Vago/métodos
3.
Med Hypotheses ; 143: 110093, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33017913

RESUMO

The COVID-19 pandemic has rapidly spread all over the world and caused a major health care crisis. About 20% of patients develop severe disease and require hospitalisation, which is associated with a high mortality rate of up to 97% in those being ventilated and respiratory failure being the leading cause of death. Despite many therapeutic agents being under current investigation there is yet no panacea available. With increasing rates of infection throughout the world, there is an urgent need for new therapeutic approaches to counteract the infection. As the nervous system has shown to be a strong modulator of respiratory function and the immune response, we want to highlight pathways involved in regulation of respiratory function, the neuro-immune axis as well as the rationale for a potential targeted treatment of fulminant acute respiratory distress syndrome via transcutaneous non-invasive vagal nerve stimulation in critically-ill COVID-19 patients.


Assuntos
Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Estimulação do Nervo Vago/métodos , Sistema Nervoso Autônomo , Betacoronavirus , Estado Terminal , Humanos , Sistema Imunitário , Pandemias , Respiração Artificial , Nervo Vago/fisiologia
4.
PLoS One ; 15(7): e0236444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702055

RESUMO

Cortical spreading depolarization (SD) waves negatively affect neuronal survival and outcome after ischemic stroke. We here aimed to investigate the effects of vagus nerve stimulation (VNS) on SDs in a rat model of focal ischemia. To this end, we delivered non-invasive VNS (nVNS) or invasive VNS (iVNS) during permanent middle cerebral artery occlusion (MCAO), and found that both interventions significantly reduced the frequency of SDs in the cortical peri-infarct area compared to sham VNS, without affecting relative blood flow changes, blood pressure, heart rate or breathing rate. In separate groups of rats subjected to transient MCAO, we found that cortical stroke volume was reduced 72 h after transient MCAO, whereas stroke volume in the basal ganglia remained unchanged. In rats treated with nVNS, motor outcome was improved 2 days after transient MCAO, but was similar to sham VNS animals 3 days after ischemia. We postulate that VNS may be a safe and efficient intervention to reduce the clinical burden of SD waves in stroke and other conditions.


Assuntos
Isquemia Encefálica/terapia , Infarto/terapia , Acidente Vascular Cerebral/terapia , Estimulação do Nervo Vago/métodos , Animais , Pressão Sanguínea , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Frequência Cardíaca/fisiologia , Humanos , Infarto/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/terapia , Ratos , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/terapia , Acidente Vascular Cerebral/fisiopatologia , Estimulação do Nervo Vago/efeitos adversos
5.
Sci Rep ; 10(1): 9472, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32528023

RESUMO

The efficacy of prior activation of an anti-inflammatory pathway called the cholinergic anti-inflammatory pathway (CAP) through vagus nerve stimulation (VNS) has been reported in renal ischemia-reperfusion injury models. However, there have been no reports that have demonstrated the effectiveness of VNS after injury. We investigated the renoprotective effect of VNS in a cisplatin-induced nephropathy model. C57BL/6 mice were injected with cisplatin, and VNS was conducted 24 hours later. Kidney function, histology, and a kidney injury marker (Kim-1) were evaluated 72 hours after cisplatin administration. To further explore the role of the spleen and splenic macrophages, key players in the CAP, splenectomy, and adoptive transfer of macrophages treated with the selective α7 nicotinic acetylcholine receptor agonist GTS-21 were conducted. VNS treatment significantly suppressed cisplatin-induced kidney injury. This effect was abolished by splenectomy, while adoptive transfer of GTS-21-treated macrophages improved renal outcomes. VNS also reduced the expression of cytokines and chemokines, including CCL2, which is a potent chemokine attracting monocytes/macrophages, accompanied by a decline in the number of infiltrating macrophages. Taken together, stimulation of the CAP protected the kidney even after injury in a cisplatin-induced nephropathy model. Considering the feasibility and anti-inflammatory effects of VNS, the findings suggest that VNS may be a promising therapeutic tool for acute kidney injury.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Cisplatino/farmacologia , Macrófagos/fisiologia , Nervo Vago/fisiopatologia , Lesão Renal Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Compostos de Benzilideno/farmacologia , Citocinas/metabolismo , Inflamação/metabolismo , Inflamação/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/fisiopatologia , Nervo Vago/metabolismo , Estimulação do Nervo Vago/métodos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
6.
Medicine (Baltimore) ; 99(23): e20315, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501977

RESUMO

BACKGROUND: Drug-resistant epilepsy (DRE) is a very tricky disorder, which greatly affects quality of life in such patients. Relevant studies suggested that vagus nerve stimulation (VNS) has potential benefits for DRE. However, there are inconsistent conclusions. The purpose of this study is to investigate whether VNS is effective and safety for DRE. METHODS: To collect comprehensive randomized controlled trials (RCTs), the following electronic databases will be retrieved: MEDLINE, EMBASE, Cochrane Library, Web of Science, PsycINFO, CINAHL, AMED, and China National Knowledge Infrastructure from the commencement of each electronic database up to the present with no language restrictions. Two authors will independently carry out all procedures of literature selection, information collection, and risk of bias assessment. Any objections will be worked out by a third author through consultation. The risk of bias for each included trial will be identified using Cochrane risk of bias tool, and statistical analysis will be performed utilizing RevMan 5.3 software. RESULTS: This study will synthesize the data from the present eligible high quality RCTs to assess whether VNS is effective and safety for DRE. CONCLUSION: This study will provide systematic evidence of VNS for the treatment of patients with DRE. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040086.


Assuntos
Epilepsia Resistente a Medicamentos/terapia , Estimulação do Nervo Vago/métodos , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Estimulação do Nervo Vago/efeitos adversos
7.
Brain Stimul ; 13(3): 800-803, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32289710

RESUMO

BACKGROUND: Studies have found that pairing vagus nerve stimulation (VNS) with motor activity accelerates cortical reorganization. This synchronous pairing may enhance motor recovery. OBJECTIVE: To develop and validate a motor-activated auricular vagus nerve stimulation (MAAVNS) system as a potential neurorehabilitation tool. METHODS: We created MAAVNS and validated its function as part of an ongoing clinical trial investigating whether taVNS-paired rehabilitation enhances oromotor learning. We compared 3 different MAAVNS EMG electrode configurations in 3 neonates. The active lead was placed over the buccinator muscle. Reference lead placements were orbital, temporal or frontal. RESULTS: The frontal reference lead produced the highest sensitivity (0.87 ± 0.07 (n = 8)) and specificity (0.64 ± 0.13 (n = 8)). Oral sucking reliably triggers MAAVNS stimulation with high confidence. CONCLUSION: EMG electrodes placed on target orofacial muscles can effectively trigger taVNS stimuli in infants in a closed loop fashion.


Assuntos
Atividade Motora/fisiologia , Reabilitação Neurológica/métodos , Reabilitação Neurológica/normas , Estimulação do Nervo Vago/métodos , Estimulação do Nervo Vago/normas , Eletromiografia/métodos , Eletromiografia/normas , Feminino , Humanos , Recém-Nascido , Reprodutibilidade dos Testes , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/normas , Nervo Vago/fisiologia
8.
Neuromodulation ; 23(6): 784-788, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32342609

RESUMO

OBJECTIVES: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic with no specific therapeutic agents and substantial mortality, and finding new treatments is critical. Most cases are mild, but a significant minority of patients develop moderate to severe respiratory symptoms, with the most severe cases requiring intensive care and/or ventilator support. This respiratory compromise appears to be due to a hyperimmune reaction, often called a cytokine storm. Vagus nerve stimulation has been demonstrated to block production of cytokines in sepsis and other medical conditions. We hypothesize that non-invasive vagus nerve stimulation (nVNS) might provide clinical benefits in patients with respiratory symptoms similar to those associated with COVID-19. MATERIALS AND METHODS: Information on two case reports was obtained via email correspondence and phone interviews with the patients. RESULTS: Both patients reported clinically meaningful benefits from nVNS therapy. In case 1, the patient used nVNS to expedite symptomatic recovery at home after hospital discharge and was able to discontinue use of opioid and cough suppressant medications. In case 2, the patient experienced immediate and consistent relief from symptoms of chest tightness and shortness of breath, as well as an improved ability to clear his lungs. CONCLUSIONS: Preliminary observations and a strong scientific foundation suggest that nVNS might provide clinical benefits in patients with COVID-19 via multiple mechanisms.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Transtornos Respiratórios/terapia , Estimulação do Nervo Vago/métodos , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Transtornos Respiratórios/diagnóstico , Transtornos Respiratórios/etiologia , Resultado do Tratamento
9.
Oxid Med Cell Longev ; 2020: 7106525, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148655

RESUMO

Objective: In renal ischemia/reperfusion injury (RIRI), nuclear factor κB (NF-κB (NF-κB (NF. Methods: Eighteen male Sprague-Dawley rats were randomly allocated into the sham group, the I/R group, and the VNS+I/R group, 6 rats per group. An RIRI model was induced by a right nephrectomy and blockade of the left renal pedicle vessels for 45 min. After 6 h of reperfusion, the blood samples and renal samples were collected. The VNS treatment was performed throughout the I/R process in the VNS+I/R group using specific parameters (20 Hz, 0.1 ms in duration, square waves) known to produce a small but reliable bradycardia. Blood was used for evaluation of renal function and inflammatory state. Renal injury was evaluated via TUNEL staining. Renal samples were harvested to evaluate renal oxidative stress, NF-κB (NF. Results: The VNS treatment reduces serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Simultaneously, the levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1-beta (IL-1ß) were significantly increased in the I/R group, but VNS treatment markedly ameliorated this inflammatory response. Furthermore, the VNS ameliorated oxidant stress and renal injury, indicated by a decrease in 3-nitrotyrosine (3-NT) formation and MDA and MPO levels and an increase in the SOD level compared to that in the I/R group. Finally, the VNS also significantly decreases NF-κB (NF. Conclusion: Our findings indicate that NF-κB activation increased iNOS expression and promoted RIRI and that VNS treatment attenuated RIRI by inhibiting iNOS expression, oxidative stress, and inflammation via NF-κB inactivation.κB (NF-κB (NF.


Assuntos
NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Traumatismo por Reperfusão/metabolismo , Estimulação do Nervo Vago/métodos , Animais , Masculino , Ratos , Ratos Sprague-Dawley
10.
Exp Neurol ; 327: 113220, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32027928

RESUMO

Vagus nerve stimulation (VNS) has rapidly gained interest as a treatment for a variety of disorders. A number of methods have been employed to stimulate the vagus nerve, but the most common relies on a cuff electrode implanted around the cervical branch of the nerve. Recently, two non-invasive methods have increased in popularity: transcutaneous cervical VNS (tcVNS) and transcutaneous auricular VNS (taVNS). Despite promising clinical results, there has been little direct comparison of these methods to stimulation delivered via an implanted device. In this study, we directly compared both non-invasive strategies to stimulation with an implanted cuff electrode on activation of the Hering-Breuer (HB) reflex, a non-invasive biomarker of A-fiber activation in the vagus. Stimulation was delivered across a wide range of parameters using tcVNS, taVNS, and an implanted cuff electrode in female rats. Activation of the HB reflex, changes in heart rate, and neck muscle twitch force were recorded. Consistent with low thresholds reported in previous studies, we found that the threshold to activate the HB reflex using an implanted cuff electrode was 0.406 ± 0.066 mA. tcVNS was capable of activating the HB reflex, but the threshold was 34.18 ± 1.86 mA, over 15 fold higher than the stimulation intensity that caused twitching of the neck muscles (2.09 ± 0.16 mA). No activation of the HB reflex was observed with taVNS at any parameters. These results describe activation of the HB reflex with each strategy and provide initial evidence regarding differences in the activation of the vagus nerve with invasive and non-invasive methods.


Assuntos
Frequência Cardíaca/fisiologia , Músculos do Pescoço/fisiologia , Fibras Nervosas Mielinizadas/fisiologia , Reflexo/fisiologia , Estimulação do Nervo Vago/métodos , Nervo Vago/fisiologia , Animais , Feminino , Contração Muscular/fisiologia , Ratos , Ratos Sprague-Dawley
11.
Sci Rep ; 10(1): 1529, 2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001763

RESUMO

Inhibiting fear-related thoughts and defensive behaviors when they are no longer appropriate to the situation is a prerequisite for flexible and adaptive responding to changing environments. Such inhibition of defensive systems is mediated by ventromedial prefrontal cortex (vmPFC), limbic basolateral amygdala (BLA), and brain stem locus-coeruleus noradrenergic system (LC-NAs). Non-invasive, transcutaneous vagus nerve stimulation (tVNS) has shown to activate this circuit. Using a multiple-day single-cue fear conditioning and extinction paradigm, we investigated long-term effects of tVNS on inhibition of low-level amygdala modulated fear potentiated startle and cognitive risk assessments. We found that administration of tVNS during extinction training facilitated inhibition of fear potentiated startle responses and cognitive risk assessments, resulting in facilitated formation, consolidation and long-term recall of extinction memory, and prevention of the return of fear. These findings might indicate new ways to increase the efficacy of exposure-based treatments of anxiety disorders.


Assuntos
Extinção Psicológica/fisiologia , Medo/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Adolescente , Adulto , Tonsila do Cerebelo/fisiologia , Condicionamento Clássico/fisiologia , Medo/psicologia , Feminino , Humanos , Inibição Psicológica , Masculino , Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Reflexo de Sobressalto/fisiologia , Nervo Vago/metabolismo , Nervo Vago/fisiologia , Estimulação do Nervo Vago/métodos , Adulto Jovem
12.
Brain Stimul ; 13(2): 494-498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31919001

RESUMO

BACKGROUND: Vagus nerve stimulation (VNS) using non-invasive approaches have attracted great attention due to their anti-epileptic, anti-depressive and pro-cognitive effects. It has been proposed that auricular transcutaneous VNS (atVNS) could benefit intellectual disability disorders, but preclinical data supporting this idea is limited. OBJECTIVE: To develop an atVNS device for mice and to test its efficacy on memory performance in naïve mice and in a mouse model for intellectual disability. METHODS: Naïve outbreed CD-1 mice and a model for fragile X syndrome, the Fmr1 knockout (Fmr1KO), were used to assess the effect of atVNS in the novel object-recognition memory performance. RESULTS: We found that atVNS significantly improves memory persistence in naïve mice. Notably, atVNS was efficacious in normalizing the object-recognition memory deficit in the Fmr1KO model. CONCLUSION: Our data show that atVNS improves memory persistence in naïve mice and in a model of intellectual disability and support further studies taking advantage of preclinical mouse models of cognitive disorders.


Assuntos
Deficiência Intelectual/fisiopatologia , Estimulação do Nervo Vago/métodos , Animais , Proteína do X Frágil de Retardo Mental/genética , Deficiência Intelectual/genética , Deficiência Intelectual/terapia , Masculino , Camundongos , Estimulação Elétrica Nervosa Transcutânea/métodos
13.
Brain Stimul ; 13(2): 470-473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31884186

RESUMO

Metabolic feedback between the gut and the brain relayed via the vagus nerve contributes to energy homeostasis. We investigated in healthy adults whether non-invasive stimulation of vagal afferents impacts energy homeostasis via efferent effects on metabolism or digestion. In a randomized crossover design, we applied transcutaneous auricular vagus nerve stimulation (taVNS) while recording efferent metabolic effects using simultaneous electrogastrography (EGG) and indirect calorimetry. We found that taVNS reduced gastric myoelectric frequency (p = .008), but did not alter resting energy expenditure. We conclude that stimulating vagal afferents induces gastric slowing via vagal efferents without acutely affecting net energy expenditure at rest. Collectively, this highlights the potential of taVNS to modulate digestion by activating the dorsal vagal complex. Thus, taVNS-induced changes in gastric frequency are an important peripheral marker of brain stimulation effects.


Assuntos
Motilidade Gastrointestinal , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Adulto , Vias Aferentes/fisiologia , Animais , Encéfalo/fisiologia , Metabolismo Energético , Humanos , Masculino , Nervo Vago/fisiologia
14.
Surgery ; 167(3): 638-645, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759624

RESUMO

BACKGROUND: Gut damage after trauma/hemorrhagic shock contributes to multiple organ dysfunction syndrome. Electrical vagal nerve stimulation is known to prevent gut damage in animal models of trauma/hemorrhagic shock by altering the gut inflammatory response; however, the effect of vagal nerve stimulation on intestinal blood flow, which is an essential function of the vagus nerve, is unknown. This study aimed to determine whether vagal nerve stimulation influences the abdominal vagus nerve activity, intestinal blood flow, gut injury, and the levels of autonomic neuropeptides. METHODS: Male Sprague Dawley rats were anesthetized, and the cervical and abdominal vagus nerves were exposed. One pair of bipolar electrodes was attached to the cervical vagus nerve to stimulate it; another pair of bipolar electrodes were attached to the abdominal vagus nerve to measure action potentials. The rats underwent trauma/hemorrhagic shock (with maintenance of mean arterial pressure of 25 mmHg for 30 min) without fluid resuscitation and received cervical vagal nerve stimulation post-injury. A separate cohort of animals were subjected to transection of the abdominal vagus nerve (vagotomy) just before the start of cervical vagal nerve stimulation. Intestinal blood flow was measured by laser Doppler flowmetry. Gut injury and noradrenaline level in the portal venous plasma were also assessed. RESULTS: Vagal nerve stimulation evoked action potentials in the abdominal vagus nerve and caused a 2-fold increase in intestinal blood flow compared to the shock phase (P < .05). Abdominal vagotomy eliminated the effect of vagal nerve stimulation on intestinal blood flow (P < .05). Vagal nerve stimulation protected against trauma/hemorrhagic shock -induced gut injury (P < .05), and circulating noradrenaline levels were decreased after vagal nerve stimulation (P < .05). CONCLUSION: Cervical vagal nerve stimulation evoked abdominal vagal nerve activity and relieved the trauma/hemorrhagic shock-induced impairment in intestinal blood flow by modulating the vasoconstriction effect of noradrenaline, which provides new insight into the protective effect of vagal nerve stimulation.


Assuntos
Traumatismos Abdominais/terapia , Mucosa Intestinal/irrigação sanguínea , Choque Hemorrágico/terapia , Estimulação do Nervo Vago/métodos , Vasoconstrição/fisiologia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/fisiopatologia , Animais , Pressão Arterial/fisiologia , Modelos Animais de Doenças , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/inervação , Masculino , Mesentério/irrigação sanguínea , Mesentério/inervação , Pescoço/inervação , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/fisiologia , Choque Hemorrágico/etiologia , Choque Hemorrágico/fisiopatologia , Vagotomia , Nervo Vago/fisiologia , Nervo Vago/cirurgia
15.
Gene ; 726: 144136, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31629817

RESUMO

Chronic systolic heart failure (CSHF) was a complex syndrome. Recently, vagus nerve stimulation (VNS), a novel treatment method, has emerged for the treatment of CSHF. therefore the aim of this study was to explore the possible mechanism of VNS treatment alleviating CSHF in rats. Firstly, we found after VNS treatment for 72 h, the level of B-type natriuretic peptide in VNS group was lower than that in CSHF group. In addition, VNS treatment induced the elevated left ventricular ejection fraction level, reduced left ventricular end diastolic volume and left ventricular end systolic volume level in VNS group, suggesting a mitigation of CSHF by VNS. Then we found the level of miR-183-3p in CSHF group was much lower than that in VNS group by High-throughput sequencing. The further results indicated that Bcl-2 interacting protein 3 like (BNIP3L) was identified as the target gene of miR-183-3p, and the expression of BNIP3L was notably reduced in rats of VNS group compared with CSHF group. Moreover, the down-regulated expression of miR-183-3p increased BNIP3L-mediated autophagy in rats of CSHF group compared with VNS group. Further mechanism findings demonstrated that up-regulation of miR-183-3p reduced the expression of BNIP3L, while down-regulation of miR-183-3p facilitated the expression of BNIP3L in H9c2 cells. miR-183-3p could also regulate autophagy by targeting BNIP3L in vitro, which was manifested by overexpression of miR-183-3p to inhibit BNIP3L-mediated autophagy. Our data demonstrated that VNS treatment benefited CSHF via the up-regulation of miRNA-183-3p, which reduced the BNIP3L-mediated autophagy, providing a new therapeutic direction for CSHF.


Assuntos
Autofagia/genética , Insuficiência Cardíaca Sistólica/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas/genética , Regulação para Cima/genética , Animais , Regulação para Baixo/genética , Masculino , Ratos , Ratos Wistar , Volume Sistólico/genética , Ativação Transcricional/genética , Estimulação do Nervo Vago/métodos , Função Ventricular Esquerda/genética
16.
Otolaryngol Clin North Am ; 53(1): 45-55, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31648824

RESUMO

The current literature on peripheral cranial nerve stimulation for the purpose of achieving therapeutic effects via altering brain activity is reviewed. Vagus nerve stimulation, which is approved for use in refractory epilepsy, is the most extensively studied cranial nerve stimulator that has direct impact on the central nervous system. Despite the recognized central effects of peripheral cranial nerve stimulation, the mechanism of action for all indications remains incompletely understood. Further research on both mechanisms and indications of central effects of cranial nerve stimulation has the potential to alleviate burden of disease in a large array of conditions.


Assuntos
Sistema Nervoso Central/fisiologia , Nervos Cranianos/fisiologia , Perda Auditiva/terapia , Neuroestimuladores Implantáveis , Estimulação do Nervo Vago/métodos , Humanos , Estimulação do Nervo Vago/instrumentação
17.
Otolaryngol Clin North Am ; 53(1): 127-143, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31685239

RESUMO

Vagal nerve stimulation (VNS) therapy is a surgical treatment that involves the implantation of a device to electrically stimulate the vagus nerve. It is indicated as an adjunctive treatment of epilepsy that is refractory to antiepileptic medications and for treatment-resistant depression. The exact mechanism by which VNS achieves its effects is not known, but various mechanisms have been proposed, including afferent vagal projections to seizure-generating regions of the brain and desynchronization of hypersynchronized cortical activity. The most common complications of VNS therapy include hoarseness, throat pain/dysphagia, coughing, and shortness of breath.


Assuntos
Transtorno Depressivo Resistente a Tratamento/terapia , Epilepsia Resistente a Medicamentos/terapia , Neuroestimuladores Implantáveis , Estimulação do Nervo Vago/métodos , Animais , Dispneia/etiologia , Rouquidão/etiologia , Humanos , Resultado do Tratamento , Estimulação do Nervo Vago/efeitos adversos
18.
Brain Stimul ; 13(1): 47-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31439323

RESUMO

BACKGROUND: Stress is associated with activation of the sympathetic nervous system, and can lead to lasting alterations in autonomic function and in extreme cases symptoms of posttraumatic stress disorder (PTSD). Vagal nerve stimulation (VNS) is a potentially useful tool as a modulator of autonomic nervous system function, however currently available implantable devices are limited by cost and inconvenience. OBJECTIVE: The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to stress. METHODS: Using a double-blind approach, we investigated the effects of active or sham tcVNS on peripheral cardiovascular and autonomic responses to stress using wearable sensing devices in 24 healthy human participants with a history of exposure to psychological trauma. Participants were exposed to acute stressors over a three-day period, including personalized scripts of traumatic events, public speech, and mental arithmetic tasks. RESULTS: tcVNS relative to sham applied immediately after traumatic stress resulted in a decrease in sympathetic function and modulated parasympathetic/sympathetic autonomic tone as measured by increased pre-ejection period (PEP) of the heart (a marker of cardiac sympathetic function) of 4.2 ms (95% CI 1.6-6.8 ms, p < 0.01), decreased peripheral sympathetic function as measured by increased photoplethysmogram (PPG) amplitude (decreased vasoconstriction) by 47.9% (1.4-94.5%, p < 0.05), a 9% decrease in respiratory rate (-14.3 to -3.7%, p < 0.01). Similar effects were seen when tcVNS was applied after other stressors and in the absence of a stressor. CONCLUSION: Wearable sensing modalities are feasible to use in experiments in human participants, and tcVNS modulates cardiovascular and peripheral autonomic responses to stress.


Assuntos
Frequência Cardíaca/fisiologia , Taxa Respiratória/fisiologia , Estresse Psicológico/terapia , Estimulação Elétrica Nervosa Transcutânea/métodos , Estimulação do Nervo Vago/métodos , Nervo Vago/fisiologia , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Adulto Jovem
19.
J Clin Neurosci ; 74: 262-264, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31447363

RESUMO

Vagus nerve stimulation (VNS) is an established tool in the psychiatric armamentarium for patients with therapy-resistant depression (TRD) with response rates of approximately 60%. So far, VNS is titrated slowly during ambulatory in-office visits. Thus, antidepressive effects can be expected after approximately six months. We report our experiences with a rapid dosing regime (RDR) with titration start shortly after VNS-implantation. We retrospectively analysed data of six patients with TRD who received VNS. Stimulation parameters were evaluated with regard to clinical side effects, heart rates (HR) and blood pressures (BP). Depressive symptoms were measured by Montgomery-Asberg Depression Rating Scale (MADRS) one week before and three months after implantation of the VNS. All patients received first stimulation between one and four days after surgery. We elevated output current using 0.25 mA titration steps. We increased output current between one and four days after the last titration. All patients received 1.0 mA output current after eight to 14 days post-surgery. HR and BP remained stable in all patients. All side effects were mild and temporary. MADRS scores were significantly lower three months after VNS-implantation (24 ±â€¯8) than one week before VNS-implantation (42 ±â€¯4; p = 0.028). The therapeutic range of VNS-parameters for antidepressive effect was reached quicker without finding increased numbers of side effects. Consequently, by using RDR the antidepressive effect of VNS-therapy for patients with TRD could be reached earlier than using slow titration. Our presented RDR might be able to significantly shorten the "clinical effect gap" due to the neurobiological and titration-related latency.


Assuntos
Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação do Nervo Vago/métodos , Adulto , Antidepressivos/uso terapêutico , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Front Immunol ; 11: 595342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33633726

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.


Assuntos
/terapia , Síndrome da Liberação de Citocina/terapia , Neuroimunomodulação/imunologia , Estimulação do Nervo Vago/métodos , Nervo Vago/imunologia , Acupuntura , Anti-Inflamatórios/farmacologia , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Inflamação/terapia , Nicotina/farmacologia , Alcaloides de Solanáceas/farmacologia
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