Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Estimulación de nervio vago en epilepsia refractaria y callosotomía previa sin mejoría. Reporte de caso / Vagus nerve stimulation in refractory epilepsy and previous callosotomy without vimprovement. Case report / Estimulação do nervo vago em epilepsia refratária e calosotomia prévia sem melhora. Relato de caso

La epilepsia refractaria tanto generalizada como focal, es una patología sumamente incapacitante, para el tratamiento de la misma se ha establecido a la callosotomía desde hace décadas como primera línea quirúrgica para su control, la cual puede presentar efectos secundarios importantes como síndrome de desconexión y pérdida de memoria, sin embargo, existen pacientes que no responden a la callosotomía y necesitan nuevas líneas de tratamiento, buscando en la estimulación de nervio vago una respuesta a su condición. Descripción del caso de estudio. Se presenta el caso de paciente masculino de 24 años de edad con antecedente patológico de convulsiones tipo tónico clónicas generalizadas confirmadas por video electroencefalograma de 24 horas, de predominio nocturno de 13 años de evolución, es sometido a 2 regímenes farmacológicos antiepilépticos diferentes en un período de 7 años de duración, posteriormente diagnosticado con epilepsia refractaria, por lo que se realiza callosotomía sin control de su cuadro clínico, el mismo año se realiza estimulación de nervio vago, presentando resultados favorables en su evolución. Conclusión. Luego de evidenciar el presente caso de estudio se concluye que el tratamiento de epilepsia refractaria con la colocación de un estimulador de nervio vago izquierdo asociado a un correcto régimen FAE es una alternativa muy eficaz para considerar en estos pacientes.

Refractory epilepsy, both generalized and focal, is an extremely disabling pathology. For its treatment, callosotomy has been established for decades as the first surgical line for its control, which can present important side effects such as disconnection and loss syndrome. by heart, however, there are patients who do not respond to callosotomy and need new lines of treatment, looking for an answer to their condition in vagus nerve stimulation. Description of the case study. We present the case of a 24-year-old male patient with a pathological history of generalized tonic-clonic seizures confirmed by a 24-hour video electroencephalogram, predominantly nocturnal for 13 years, undergoing 2 different antiepileptic pharmacological mechanisms over a period of 7 years in duration, later diagnosed with refractory epilepsy, for which callosotomy was performed without control of its clinical picture, the same year vagus nerve stimulation was performed, presenting favorable results in its evolution. Conclution. After evidencing the present case study, it is concluded that the treatment of refractory epilepsy with the placement of a left vagus nerve stimulator associated with a correct AED regimen is a very effective alternative to consider in these patients.

A epilepsia refratária, tanto generalizada quanto focal, é uma patologia extremamente incapacitante. Para seu tratamento, a calosotomia se estabeleceu há décadas como a primeira linha cirúrgica para seu controle, que pode apresentar importantes efeitos colaterais como desconexão e síndrome de perda., há pacientes que não respondem à calosotomia e precisam de novas linhas de tratamento, buscando resposta para sua condição na estimulação do nervo vago. Descrição do estudo de caso. Apresentamos o caso de um doente do sexo masculino, 24 anos, com antecedentes patológicos de crises tónico-clónicas generalizadas confirmadas por videoeletroencefalograma de 24 horas, predominantemente nocturnas há 13 anos, submetido a 2 mecanismos farmacológicos antiepilépticos diferentes ao longo de 7 anos de duração, posteriormente diagnosticada com epilepsia refratária, para a qual foi realizada calosotomia sem controle de seu quadro clínico, no mesmo ano foi realizada estimulação do nervo vago, apresentando resultados favoráveis em sua evolução. Conclusão. Depois de evidenciar o presente estudo de caso, conclui-se que o tratamento da epilepsia refratária com a colocação de um estimulador de nervo vago esquerdo associado a um esquema correto de DEA é uma alternativa muito eficaz a ser considerada nesses pacientes.

Neuromodulação Vagal Auricular e sua Aplicabilidade em Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida / Auricular Vagal Neuromodulation and its Application in Patients with Heart Failure and Reduced Ejection Fraction

Resumo Fundamento O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. Objetivos Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. Métodos Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. Resultados Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. Conclusão A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Abstract Background The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. Objectives To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. Methods Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. Results In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. Conclusion taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Effect of transcutaneous auricular vagus nerve stimulation combined with robot-assisted therapy on upper limb function of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) combined with robot-assisted therapy on upper limb function of subacute stroke patients. MethodsFrom March, 2022 to March, 2023, 60 subacute stroke patients from Dushu Lake Hospital and the First People's Hospital of Kunshan were randomly divided into control group (n = 20), robot group (n = 20) and combined group (n = 20). All the groups received conventional treatments including medication, physical therapy and occupational therapy; the robot group received sham taVNS combined with hand robot-assisted therapy; while the combined group received taVNS combined with hand robot-assisted therapy, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and hand part, the root mean square (RMS) electromyography of the extensor carpi radialis and extensor digitorum muscles during contraction, and the latency and amplitude of transcranial magnetic stimulation motor-evoked potential (TMS-MEP) before and after treatment. ResultsAfter treatment, the scores of FMA-UE and hand part, RMS of the extensor carpi radialis and extensor digitorum muscles, and latency and amplitude of TMS-MEP improved in all the groups (t > 2.099, P < 0.05); and they were the best in all indicators in the combined group (F > 9.106, P < 0.001). ConclusiontaVNS combined with robot-assisted therapy can promote central nervous system remodeling and further improve upper limb function in stroke patients.

Effect of transcutaneous auricular vagus nerve stimulation combined with bilateral arm training on upper limb motor function of stroke patients / 中国康复理论与实践

ObjectiveTo investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) combined with bilateral arm training (BAT) on upper limb motor function of hemiplegic stroke patients. MethodsFrom January, 2021 to January, 2022，105 stroke patients from Zhejiang Provincial People's Hospital were randomly divided into taVNS group (n = 35), BAT group (n = 35) and combined group (n = 35). All the patients received routine rehabilitation, while taVNS group received taVNS, BAT group received BAT, and the combined group received both taVNS and BAT, for eight weeks. The root mean square (RMS) of surface electromyography in deltoid, triceps brachii and extensor carpi was measured, and the scores of Box and Block Test (BBT), and Fugl-Meyer Assessment-Upper Extremities (FMA-UE) were obtained before and after treatment. ResultsThe RMS of all these muscles, and the scores of BBT and FMA-UE improved in all the three groups after treatment (|t| > 6.124, P < 0.001), and they were improved the most in the combined group (F > 18.162, P < 0.001). ConclusionBoth taVNS and BAT can enhance the muscle strength on the affected upper limb, increase the hand flexibility, and improve upper limb motor function of stroke patients, while the combination of both methods is more effective.

Efeito da estimulação elétrica transcutânea do nervo vago na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19: estudo de protocolo para um ensaio clínico, controlado, randomizado e cego / Efecto de la estimulación eléctrica transcutánea del nervio vago sobre la inflamación, la modulación autonómica cardiac y la evolución clínica de pacientes con COVID-19: estudio de protocolo para un ensayo clínico, controlado, aleatorizado y ciego / Effects of transcutaneous auricular vagus nerve stimulation on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19: protocol for a clinical, controlled, randomized, and blind trial

RESUMO O objetivo deste estudo é avaliar o efeito da estimulação elétrica transcutânea do nervo vago (EETNV) na inflamação, modulação autonômica cardíaca e evolução clínica dos pacientes com COVID-19. Trata-se de um ensaio clínico, controlado por sham, randomizado e cego, no qual participarão 52 indivíduos hospitalizados com diagnóstico de COVID-19, que serão randomizados em dois grupos de tratamento: grupo experimental (tratamento médico usual associado à EETNV ativa) ou grupo-controle (tratamento médico usual associado à EETNV sham). A EETNV será realizada por meio de um estimulador elétrico neuromuscular (modelo Dualpex 071 da Quark Medical Products), com o eletrodo de estimulação posicionado sobre o tragus esquerdo, com corrente alternada, frequência de 30Hz e variação de 50%, intensidade ajustada para o limiar sensorial do paciente, com duração de 90 minutos cada sessão de estimulação, duas vezes ao dia, durante sete dias consecutivos, totalizando 14 sessões. Serão avaliados pré e pós-intervenção o nível de interleucina-6 (IL-6) e interleucina-10 (IL-10), cortisol e proteína C reativa (PCR), pressão arterial, variabilidade da frequência cardíaca pelos parâmetros de baixa frequência (BF), alta frequência (AF) e pela razão da baixa e alta frequência (BF/AF), além de evolução clínica dos pacientes, incluindo o nível de ansiedade e depressão, cujos dados serão obtidos por meio de prontuários e questionários. Será realizado também um acompanhamento 7 e 14 dias após o término das intervenções para verificar a evolução clínica, incluindo nível de ansiedade e depressão, e durante seis meses serão avaliadas memória e atenção.

RESUMEN El objetivo de este estudio es evaluar el efecto de la estimulación eléctrica transcutánea del nervio vago (EETNV) sobre la inflamación, la modulación autonómica cardíaca y la evolución clínica de pacientes con COVID-19. Se trata de un ensayo clínico, controlado por simulado, aleatorizado y ciego, en el que participarán 52 individuos hospitalizados diagnosticados de COVID-19, que serán aleatorizados en dos grupos de tratamiento: grupo experimental (tratamiento médico habitual asociado a la EETNV activa) o grupo control (tratamiento médico habitual asociado a la EETNV simulada). La EETNV se realizará mediante un estimulador eléctrico neuromuscular (modelo Dualpex 071 de Quark Medical Products), con el electrodo de estimulación colocado en el trago izquierdo, con corriente alterna, frecuencia de 30Hz y 50% de variación, intensidad ajustada al umbral sensorial del paciente, con una duración de 90 minutos cada sesión de estimulación, dos veces al día, durante siete días consecutivos, lo que totaliza 14 sesiones. Se evaluarán antes y después de la intervención la interleucina-6 (IL-6) y la interleucina-10 (IL-10), el cortisol y la proteína C reactiva (PCR), la presión arterial, la variabilidad de la frecuencia cardíaca por los parámetros de baja frecuencia (BF), alta frecuencia (AF) y razón de baja y alta frecuencia (BF/AF), así como la evolución clínica de los pacientes, incluidos los parámetros de ansiedad y depresión cuyos datos se obtendrán de historias clínicas y cuestionarios. También se realizará un seguimiento de 7 y 14 días tras finalizadas las intervenciones para verificar la evolución clínica, incluidos el nivel de ansiedad y de depresión, y durante seis meses se evaluará la memoria y la atención.

ABSTRACT This study aims to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation, cardiac autonomic modulation, and clinical evolution of patients with COVID-19. This is a clinical, sham-controlled, randomized, and blind trial, in which 52 hospitalized individuals diagnosed with COVID-19 will participate. They will be randomized into: experimental group (usual medical treatment associated with active taVNS) and control group (usual medical treatment associated with sham taVNS). The taVNS will be performed by a neuromuscular electric stimulator (Dualpex model 071 of Quark Medical Products), with the stimulation electrode positioned on the left tragus, with alternating current, at a 30Hz frequency with 50% variation. Intensity will be adjusted to the patient's sensory threshold, with 90-minutes-long stimulation sessions, happening twice per day for seven consecutive days, totaling 14 sessions. Interleukin-6 (IL-6) and interleukin-10 (IL-10), cortisol and C-reactive protein (CRP), blood pressure, heart rate variability (HRV) by low frequency (LF), high frequency (HF) and low and high frequency ratio (LF/HF) parameters will be evaluated before and after the intervention, as well as patients' clinical evolution-including anxiety and depression levels-whose data will be obtained through medical records and questionnaires. A follow-up will also be performed seven and 14 days after the end of the interventions to verify the clinical evolution, including anxiety and depression levels. Memory and attention levels will be evaluated for six months.

A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Vagus nerve stimulation: a novel method for obesity treatment? / 中华内分泌代谢杂志

Obesity is one of the most serious global public health issue. In addition to advocating healthy lifestyle, scientists are devoted to developing healthy and effective ways to tackle obesity. In recent years, vagus nerve stimulation has been revealed to have potential therapeutic effect on obesity, which may be related to regulating endocrine hormones and body metabolism, affecting different nerve functions, regulating inflammatory and immune pathways, adjusting intestinal flora and circadian rhythm, and so on. Current researches focus on percutaneous stimulation(auricular vagus nerve stimulation), subcutaneous stimulation(cervical and abdominal vagus nerve stimulation), and gastrointestinal stimulation(the implantation of vagus nerve stimulation device and vagus nerve blocking device). Growing number of studies have confirmed that these stimulation methods have favorable effects on obesity with less side effects. Moreover, the mechanism of Chinese traditional acupuncture for obesity treatment is similar to that of vagus nerve stimulation. Most of vagus nerve stimulation is conveyed via physical therapy. It is highly feasible and theoretically has few side effects, therefore is easy to be accepted by obese subjects and may become a promising approach for obesity treatment.

Effect of vagus nerve stimulation by electroacupuncture on GFAP and NeuN in hippocampal of juvenile rats with depression induced by chronic unpredictable stress / 中国医师杂志

Objective:To analyze the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) antigen in hippocampus based on the depression model of juvenile rats caused by chronic unpredictable stress (CUS), and to explore the effect of electroacupuncture vagus nerve on CUS depression model.Methods:Six juvenile SD rats were selected as the control group (without any stimulation), and the rest were divided into CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group by random number method after CUS modeling, with 6 rats in each group. Fluoxetine group was given 10 mg/kg fluoxetine intervention; control group and CUS group were given the same amount of normal saline intervention; In the electroacupuncture group, the distal vagus nerve was stimulated after ligation, while in the pseudo stimulation group, only vagus nerve was isolated without electrical stimulation. After 28 d of intervention, the five groups were subjected to Open-field Test and Sucrose Preference Test. Hippocampal neurons were detected by hematoxylin and eosin (HE) staining, and the expressions of GFAP and NeuN in hippocampal were detected by immunohistochemistry.Results:After CUS modeling and before intervention, the number of vertical and horizontal movements, sucrose consumption and sucrose preference in CUS group, pseudo stimulation group, fluoxetine group and electroacupuncture group were significantly lower than those in the control group (all P<0.01); After the intervention, the above indexes in CUS group and pseudo stimulation group were still lower than those in the control group (all P<0.01), but the above indexes in fluoxetine group and electroacupuncture group were significantly higher than those in CUS group and pseudo stimulation group (all P<0.01). HE staining showed that the arrangement of hippocampal neurons in CUS group and pseudo stimulation group were loose, and there were cell swelling and pyknosis, which was significantly improved in fluoxetine group and electroacupuncture group. Immunohistochemical results showed that compared with the control group, the expression of GFAP increased and NeuN decreased in the hippocampus of CUS group and pseudo stimulation group (all P<0.01); Compared with CUS group and pseudo stimulation group, the expression of GFAP decreased and NeuN increased in fluoxetine group and electroacupuncture group (all P<0.01). Conclusions:Electroacupuncture of vagus nerve can obviously improve the depression symptoms of juvenile rats, which is similar to fluoxetine, and may be related to regulating the expression of GFAP and Neun in hippocampus.

Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia.@*METHODS@#Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO15) and Shen (CO10) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately.@*RESULTS@#After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01).@*CONCLUSION@#The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.

Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia / 中国针灸

OBJECTIVE@#To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI).@*METHODS@#A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain.@*RESULTS@#After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01).@*CONCLUSION@#taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

Vagus Nerve Stimulation in the Treatment of Dravet Syndrome / 罕见病研究

Dravet syndrome is a epileptic syndrome characterized by drug-resistant epilepsy occuring at childhood. It is often accompanied by status epilepticus and cognitive and language impairment appearing gradually as the disease progresses. The effect of antiepileptic drugs and resection epilepsy surgery on Dravet syndrome is poor although neuromodulation surgery, especially vagus nerve stimulation, is an effective and feasible treatment for Dravet syndrome. In this article we reported a case of Dravet syndrome treated with vagus nerve stimulation, relevant literature was reviewed and summarized at the same time. A total of 141 cases of Dravet treated by vagus nerve stimulation were collected, and the overall effective rate was 53.9%.

Effects of vagus nerve stimulation on postoperative cognitive dysfunction and role of hippocampal insulin growth factor 1 signaling pathway in aged mice / 中华麻醉学杂志

Objective:To investigate the effects of vagus nerve stimulation on postoperative cognitive dysfunction and the role of hippocampal insulin growth factor 1 signaling pathway in aged mice.Methods:Seventy-five clean-grade C57 mice of both sexes, aged 21-23 months, weighing 28-34 g, were divided into 5 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O), operation + vagus nerve stimulation group (group O+ V), operation + IGF-1 siRNA group (group O+ I) and operation + vagus nerve stimulation + IGF-1 siRNA group (group O+ V+ I). Group O underwent exploratory laparotomy.Group O+ V received a 30-min electrical stimulation of the vagus nerve (intensity 0.5 mA, frequency 20 Hz, time 30 s, 6 times, interval 5 min) after the end of exploratory laparotomy.Group O+ I underwent exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Group O+ V+ I underwent electrical vagus nerve stimulation after exploratory laparotomy and inhaled IGF-1 siRNA solution 10 μl intranasally at 24 h before surgery and 24 and 48 h after surgery.Morris water maze tests were performed on 14-18 days after operation.On day 7 after operation, the mice were sacrificed and the hippocampus was obtained for determination of the expression of Bax, ionized calcium-binding adapter molecule 1 (Iba-1), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 1 receptor (IGF1R), phosphorylated IGF1R (p-IGF1R), interleukin-1beta (IL-1β) and activated caspase-3 by Western blot. Results:Compared with group S, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened on days 16-18 after operation, the frequency of crossing the platform was increased, the time spent in the target quadrant was prolonged, the expression of IGF-1 and p-IGF1R was up-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was down-regulated in group O+ V ( P<0.05), and no significant change was found in the parameters mentioned above in group O+ I ( P>0.05). Compared with group O+ V, the escape latency was significantly prolonged on days 16-18 after operation, the frequency of crossing the platform was reduced, the time spent in the target quadrant was shortened, the expression of IGF-1 and p-IGF1R was down-regulated, and the expression of Iba-1, IL-1β, activated caspase-3 and Bax was up-regulated in group O+ V+ I ( P<0.05). There was no significant difference in the expression of IGF1R among the four groups ( P>0.05). Conclusions:Vagus nerve stimulation can reduce postoperative cognitive dysfunction, and the mechanism is related to activation of IGF-1 signaling pathway and reduction of hippocampal neuroinflammation and neuronal apoptosis in aged mice.

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application / 神经科学通报·英文版

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.

Effects of electrical stimulation of vagus nerve on α7 nicotinic acetylcholine receptor and inflammatory factors in ischemic stroke model mice / 中华行为医学与脑科学杂志

Objective:To explore the effect of α7 nicotinic acetylcholine receptor (α7nAchR) and changes of inflammatory factors during vagus nerve electrical stimulation in ischemic stroke model mice.Methods:Ninety SPF grade mice were randomly divided into sham operation+ vagus nerve electrical stimulation group (sham+ VNS group), model group (permanent middle cerebral artery occlusion group, pMCAO group), model+ vagus nerve electrical stimulation (pMCAO+ VNS group) and model group+ α7nAchR agonist group (pMCAO+ P group), model + vagus nerve electrical stimulation+ α7nAchR antagonist (pMCAO+ VNS+ A group), model+ vagus nerve electrical stimulation+ α7nAchR antagonist placebo group (pMCAO+ VNS+ AC group), with 15 mice in each group. The changes of vital signs of mice in each group were monitored during modeling.At 7, 14 and 21 days after successful modeling, neurological severity score (NSS) and adhesive removal test were used to evaluate the neurological deficit of mice.Immunofluorescence and Western blot were used to detect the expression of α7nAchR and its neural cell localization. ELISA was used to detect the level of TNF-α and IL-6. Prism 8.0 software was used for statistical analysis, and one-way ANOVA was used to analyze the physiological parameters during modeling.Repeated measurement ANOVA was used to compare the neurobehavioral score results, and t-test was used to compare the protein level and fluorescence intensity. Results:(1)The results of repeated measurement ANOVA showed that the interaction between group and time in NSS score was not significant ( F=0.91, P>0.05), and the group main effect ( F=46.68, P<0.05) and time main effect ( F=25.56, P<0.05) were significant. The results of Tukey's test showed that the NSS scores of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group (both P<0.05). There was no significant difference between pMCAO+ P group and pMCAO+ VNS group ( P>0.05). The NSS scores in pMCAO+ VNS+ A group were higher than that in pMCAO+ VNS group ( P<0.05), and significantly lower than that in pMCAO+ VNS+ AC group ( P<0.05). In the adhesive removal test, the interaction between group and time in the adhesive tape contact time and tear off time of mice was not significant ( F=0.67, 0.71, all P>0.05), and the group main effect ( F=30.12, 42.46, all P<0.05) and time main effect ( F=52.18, 47.34, all P<0.05) of mice in each group were significant.Tukey's test showed that the adhesive removal test on the 21st day, the adhesive tape contact time and tear off time of pMCAO+ VNS group were significantly shorter than those of pMCAO group (both P<0.05), and there was no significant difference between pMCAO+ P group and pMCAO+ VNS group (both P>0.05). (2)Western blot showed that compared with pMCAO group (0.36±0.01), the expression of α7nAchR in pMCAO+ VNS group (0.83±0.03) and pMCAO+ P group (0.67±0.02) increased ( t=13.53, 16.08, both P<0.01). The expression of α7nAchR in PCAO+ VNS+ A group (0.37±0.01) was significantly lower than that in PCAO+ VNS group ( t=12.88, P<0.01). Immunofluorescence results also showed that compared with pMCAO group (3.75±0.19), the expression of α7nAchR in pMCAO+ VNS group (8.96±0.48) and pMCAO+ P group increased (8.17±0.64) ( t=10.04, 6.67, both P<0.05). Immunofluorescence results also showed that compared with the pMCAO group (3.75±0.19), the expression of α7nAchR protein in the brain tissue of mice in the pMCAO+ VNS group and pMCAO+ P group increased ((8.96±0.48), (8.17±0.64), t=10.04, 6.67, all P<0.05). (3)The results of ELISA showed that compared with pMCAO group, the levels of TNF-a and IL-6 in serum and tissue supernatant of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group ( t=23.28, 15.30, 12.26, 11.08; all P<0.05). TNF in serum and tissue supernatant of mice in pMCAO+ VNS+ A group The levels of IL-6 in serum and tissue supernatant were significantly higher than those in pMCAO+ VNS group ( t=12.70, 11.01, 11.69, 17.37; all P<0.05) and pMCAO+ VNS+ AC group ( t=12.29, 11.07, 14.61, 29.27; all P<0.05). Conclusion:VNS may reduce inflammation by increasing the expression of α7nAchR protein in brain tissue, thereby playing a certain neuroprotective effect on ischemic stroke.

Left-sided vagus nerve stimulation improves cardiopulmonary resuscitation outcomes in rats as effectively as right-sided vagus nerve stimulation / 世界急诊医学杂志（英文）

@#BACKGROUND: Our group previously reported that right-sided vagus nerve stimulation (RVNS) significantly improved outcomes after cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). However, whether left-sided vagus nerve stimulation (LVNS) could achieve the same effect as RVNS in CPR outcomes remains unknown. METHODS: A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fibrillation (VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation (ROSC), and their health and behavior were evaluated every 24 hours. RESULTS: Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation (VNS) decreased the serum levels of tumor necrosis factor-alpha (TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with findings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no significant difference in efficacy when comparing the laterality of stimulation. CONCLUSIONS: LVNS may have similar effects as RVNS on improving outcomes after CPR.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy / 中南大学学报(医学版)

OBJECTIVES@#Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy.@*METHODS@#A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data.@*RESULTS@#After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, @*CONCLUSIONS@#VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

Autonomic nervous intervention in treatment of heart failure: Recent progress / 第二军医大学学报

Heart failure is a complicated pathophysiological syndrome. Balancing autonomic nervous activity and inhibiting myocardial remodeling are important methods for improving long-term efficacy in patients with heart failure. Pharmacologic management has been greatly developed, for example, the use of β-blockers is intended to inhibit the toxic effect of sympathetic activation on the heart and has become a classic treatment for heart failure. However, the incidence of heart failure is still on the rise and survivability is persistently reduced. In recent years, surgical treatments for inhibiting excessive activation of the sympathetic nervous system have emerged, such as vagus nerve stimulation, baroreceptor activation therapy. Some methods have obtained significant benefits in animal experiments and preliminary clinical study. It is essential to further verify the role of the above treatments in patients with heart failure in clinical trials.