Inhibiting effect of vagal nerve stimulation to seizures in epileptic process of rats

Objective Our previous work suggested that sensitivity of hippocampal neurons is changed in process of epileptic activities,and closely parallel to the dynamic characteristic of epileptic activity of the neurons.This study investigated the sensitivity of epileptic brain to vagal nerve stimulation（VNS）in epileptic process.Methods Epileptic model was evoked by penicillin.Left vagal nerves were stimulated to inhibit the seizures induced by penicillin.The electrocorticography（ECoG）and electromyography（EMG）were recorded to analyze inhibiting effect of VNS in epileptic process.Results It was found that VNS could inhibit the seizures caused by penicillin,and the inhibiting effect of VNS to seizures increased as the vagal nerve stimulating time prolonged.It was also found that the inhibiting effect of VNS to seizures decreased in epileptic process.Conclusion The results suggested that the sensitivity of epileptic brain to VNS was different in epileptic process.The inhibiting effect of VNS to seizure decreased as the development of seizures.

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

AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable 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-DVCvagus-gastric neural pathway.

Vagal nerve stimulation in prevention and management of coronary heart disease

Coronary heart disease (CHD) that is due to atherosclerosis is associated with low-grade systemic inflammation. Congestive cardiac failure and arrhythmias that are responsible for mortality in CHD can be suppressed by appropriate vagal stimulation that is anti-inflammatory in nature. Acetylcholine, the principal vagal neurotransmitter, is a potent anti-inflammatory molecule. Polyunsaturated fatty acids (PUFAs) augment acetylcholine release, while acetylcholine can enhance the formation of prostacyclin, lipoxins, resolvins, protectins and maresins from PUFAs, which are anti-inflammatory and anti-arrhythmic molecules. Furthermore, plasma and tissue levels of PUFAs are low in those with CHD and atherosclerosis. Hence, vagal nerve stimulation is beneficial in the prevention of CHD and cardiac arrhythmias. Thus, measurement of catecholamines, acetylcholine, various PUFAs, and their products lipoxins, resolvins, protectins and maresins in the plasma and peripheral leukocytes, and vagal tone by heart rate variation could be useful in the prediction, prevention and management of CHD and cardiac arrhythmias.

Altered physiology of gastrointestinal vagal afferents following neurotrauma

The adaptability of the central nervous system has been revealed in several model systems.Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function.In both types of neurotrauma,traumatic brain injury and spinal cord injury,the primary parasympathetic control to the gastrointestinal tract,the vagus nerve,remains anatomically intact.However,individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions.Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury.While the vagal efferent output remains capable of eliciting motor responses following injury,evidence suggests impairment of the vagal afferents.Since sensory input drives motor output,this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma.

AN UNUSUAL BILATERAL VAGAL PARAGANGLIOMAS: ONE CASE STUDY

VAGAL paraganglioma （VP） is an uncommon neoplasm originating from neural crest paraganglion cells located along the vagus nerve, repre-senting less than 5 % of all paragangliomas of the head and neck Despite improvement in microsurgical techniques,

Respiratory modulation of cardiac vagal tone in Lyme disease

AIM: To conduct the first systematic test of the hypothesis that modulation of cardiac vagal tone is impaired in Lyme disease.METHODS: The response of cardiac vagal tone to respiratory modulation was measured in 18 serologically positive Lyme disease patients and in 18 controls.RESULTS: The two groups were matched in respect of age,sex,body mass,mean arterial blood pressure,mean resting heart rate and mean resting cardiac vagal tone. The mean maximum cardiac vagal tone during deep breathing in the Lyme disease patients [11.2(standard error 1.3)] was lower than in the matched controls [16.5(standard error 1.7); P = 0.02].CONCLUSION: Respiratory modulation of cardiac vagal tone is impaired in Lyme disease,which suggests that Lyme disease may directly affect the vagus nerve or the brainstem.

How to properly evaluate cardiac vagal tone in oncology studies:a state-of-the-art review

Heart rate variability(HRV)analysis provides an assessment of cardiac vagal tone and consequently global cardiac health as well as systemic condition.In systemic diseases such as cancer and during treatments that affect the whole body,like chemotherapy,the vagus nerve activity is low and deregulated.Some studies focus on using HRV to predict mortality in oncology.However,in cancer patients,systemic alterations substantially increase artifacts during HRV measurement,especially atrial ectopic beats.Moreover,HRV may be altered by various factors(duration and time of measurement,breathing,drugs,and other confounding factors)that alter each metric in different ways.The Standard Deviation of all Normal to Normal intervals(SDNN)is the most commonly used metric to evaluate HRV in oncology,but it does not appear to be specific to the cardiac vagal tone.Thus,cardiac vagal activity diagnosis and vital prognosis of cancer patients can be biased.Our review presents the main HRV metrics that can be currently used in oncology studies and their links with vagus nerve and cancer.We present the influence of external factors and the required duration and time of measurement.Considering all these parameters,this review proposes seven key points for an assessment of HRV and cardiac vagal tone in patients with cancer.

针灸视域下的神经—免疫调节

针灸作为中国传统医学体系中独具特色的诊疗技法,通过体表特定区域的物理刺激,调动神经、内分泌和免疫等多系统应答,促进机体自稳态修复。针灸对生物体机能多层次的调控特点,蕴含着其原创性的生命科学价值,有待于深入探究和阐明。本文结合“神经—免疫”交互作用的研究背景,在梳理针灸引发“躯体—自主神经”反射调节规律的基础上,总结了针灸不同穴位通过“迷走—肾上腺”轴或“交感—脾脏”轴改善系统性炎症的作用环路,明确了针灸“神经—免疫”调节的效应规律和影响因素。并指出:针灸刺激体表“纵横”位域引起相对特异的自主神经活动,是其发挥区域性或全身性免疫调控的关键。现阶段,针灸的“神经—免疫”调控虽已取得瞩目进展,但该领域的基础研究和应用推广仍处于“萌芽”阶段,倡议通过有组织、有目的的多学科交叉合作,继续完善针灸“精准”干预实现“神经—免疫”调控的系统生物学内涵,加快推进相关科研成果转化和针灸装备研发,不断拓展针灸在改善人体内脏功能和免疫—炎性反应中的应用价值。

预防性使用阿托品对无痛膀胱镜检查术中诱发迷走神经反射的防治效果

目的:探讨预防性使用阿托品对无痛膀胱镜检查术中诱发迷走神经反射的防治效果。方法:选择2022年10月—2023年11月在青岛大学医学院松山医院行静脉复合全麻下无痛膀胱镜检查的144例患者作为研究对象,采用完全随机化分组的随机数表法将144例入选病例分为对照组、观察组,各72例。两组均采用地佐辛(0.05 mg/kg)复合1%丙泊酚(1.5~2.0 mg/kg)进行麻醉诱导,待患者睫毛反射消失时开始进行膀胱镜检查。术中丙泊酚以3~6 mg/(kg·h)维持,患者术中如发生体动,则追加丙泊酚0.5 mg/kg,直至检查结束。对照组在1%丙泊酚20 mL中加入0.9%氯化钠溶液1 mL,观察组在1%丙泊酚20 mL中加入阿托品1 mg。两组在麻醉过程中出现心率低于50次/min时,静脉注射阿托品0.5 mg,当血压降低超过20%时静脉注射麻黄碱6 mg。比较两组无痛膀胱镜检查操作时间、术后清醒时间、丙泊酚用量、术中迷走神经反射及并发症发生情况。结果:观察组无痛膀胱镜检查操作时间短于对照组,差异有统计学意义(P<0.01);两组术后清醒时间、丙泊酚用量比较,差异无统计学意义(P>0.05)。观察组术中发生迷走神经反射发生率低于对照组,差异有统计学意义(P<0.01)。两组均无严重并发症,对照组均经及时应用阿托品、麻黄碱等积极抢救治疗而痊愈。结论:无痛膀胱镜检查中预防性使用阿托品不仅有利于缩短操作时间、有利于呼吸管理,更有利于预防迷走神经反射,减少并发症,具有较高的安全性。

Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Misinterpretation of sleep-induced second-degree atrioventricular block

A number of publications have claimed that Mobitz type Ⅱ atrioventricular block(AVB)may occur during sleep.None of the reports defined type Ⅱ AVB and representative electrocardiograms were either misinterpreted or missing.Relatively benign Wenckebach type Ⅰ AVB is often misdiagnosed as Mobitz type Ⅱ which is an indication for a pacemaker.Review of the published reports indicates that Mobitz type II AVB does not occur during sleep when it is absent in the awake state.Conclusion:There is no proof that sleep is associated with Mobitz type Ⅱ AVB.

针刺中脘调节胃运动的神经通路研究进展

中脘穴是调节胃动力的常用穴,针刺疗效显著,临床应用广泛。本文通过整理近15年参与针刺中脘调节胃运动的神经核团及相关通路相关研究发现:(1)针刺中脘双向调节胃运动的效应与针刺时间长短密切相关,其内在机制可能与神经反射调节、神经—内分泌调节存在时效性差异有关。(2)杏仁核、海马是针刺中脘调节情绪和胃运动的共同响应核团。(3)针刺中脘可经辣椒素受体-Aδ与C纤维—脊髓、脊髓—交感神经、海马谷氨酸-N-甲基-D-天冬氨酸受体亚基NR1、CeA(γ-氨基丁酸)-室旁核、室旁核(胃动素)—迷走神经有核复合体—迷走神经等神经机制调节胃运动;也可经DVC-NMDAR亚基NR1—外周NO等神经—内分泌途径调节胃运动。研究结果表明针刺中脘对胃运动的调节是多方面、多维度、多靶点的综合调控。今后的研究应规范实验针刺操作,优化实验方案,结合脑科学技术综合、整体、动态探究针刺效应机制,进一步揭示针灸疗法中近治作用的内在机理。

3-吲哚丙酸通过迷走神经调控动物采食的肠-脑轴机制

【目的】食欲是影响采食量的最重要因素,来自中枢和外周的多种信号经下丘脑食欲中枢感应和整合后调控采食,肠-脑轴在动物食欲调控中发挥重要作用。旨在揭示3-吲哚丙酸调控动物采食的肠-脑轴机制,对揭示缓解动物厌食具有参考价值。【方法】以21只8周龄C57BL/6J雄性小鼠为试验对象,通过灌服0,1,10 mg/kg3-吲哚丙酸,检测其对小鼠采食量和体增重的影响;并采用膈下迷走神经切除术、c-Fos免疫荧光和药物遗传学等技术,探究3-吲哚丙酸通过迷走神经介导的肠-脑轴调控动物采食的神经环路。【结果】(1)与对照组相比,灌服10 mg/kg 3-吲哚丙酸可显著提高小鼠3 h的采食量(P<0.05)和激活孤束核神经元(P<0.01)神经元兴奋性,化学遗传学抑制孤束核神经元可阻断3-吲哚丙酸促采食的作用;(2)3-吲哚丙酸抑制迷走传入神经兴奋性(P<0.001),膈下迷走神经切断或化学遗传学激活NG神经节均可消除3-吲哚丙酸促采食的作用。【结论】3-吲哚丙酸通过抑制肠道迷走传入神经兴奋性,从而激活孤束核神经元,提高动物采食量。

Blockade of Na^+/H^+ exchanger type 3 causes intracellular acidification and hyperexcitability via inhibition of pH-sensitive K^+ channels in chemosensitive respiratory neurons of the dorsal vagal nucleus in rats

Extracellular pH （pHe） and intracellular pH （pHi） are important factors for the excitability of chemosensitive central respiratory neurons that play an important role in respiration and obstructive sleep apnea. It has been proposed that inhibition of central Na^＋/ H^＋ exchanger 3 （NHE-3）, a key pHi regulator in the brainstem, decreases the pH, leading to membrane depolarization for the maintenance of respiration. However, how intracellular pH affects the neuronal excitability of respiratory neurons remains largely unknown. In this study, we showed that NHE-3 mRNA is widely distributed in respiration-related neurons of the rat brainstem, including the dorsal vagal nucleus （DVN）. Whole-cell patch clamp recordings from DVN neurons in brain slices revealed that the standing outward current （Iso） through pH-sensitive K^＋ channels was inhibited in the presence of the specific NHE-3 inhibitor AVE0657 that decreased the pHi. Exposure of DVN neurons to an acidified PIle and AVE0657 （5 μmol/L） resulted in a stronger effect on firing rate and Iso than acidified pHe alone. Taken together, our results showed that intracellular acidification by blocking NHE-3 results in inhibition of a pH- sensitive K^＋ current, leading to synergistic excitation of chemosensitive DVN neurons for the regulation of respiration.

Blood Pressure Change in Intrafascicular Vagal Activities

Baroreflex plays a significant role in modulating blood pressure for the human body.It is known that activation of the vagal nerve related to baroreflex can lead to reductions of blood pressure.However,how the vagal activities quantitatively relate with blood pressure can hardly be achieved.Here fine carbon nanotube yarn(CNTy)electrodes were adopted for recording intrafascicular vagal activities,synchronized with measurement of arterial blood pressure in a rat.Together with a novel algorithm,the results preliminarily quantified that there were six clusters of neural spikes within recorded vagal activities,and the number of individual vagal spikes correspondingly varied with blood pressure.Especially for Cluster 2,the neural activations decreased with arterial blood pressure increasing.This study can shed lights on the quantified neural mechanism underlying the control of vagal activities on blood pressure,and guide the vagal-nerve neuromodulation for treating hypertension.

全程护理干预对预防冠脉介入诊疗术后拔鞘并发迷走神经反射的干预效果

目的探讨实施全程护理干预对预防冠状动脉介入诊疗术后拔鞘并发迷走神经反射的干预效果。方法按照随机数字表法将2022年10月至2023年10月于我院行冠状动脉介入诊疗的患者200例分为两组,各100例。采用常规护理干预的患者纳入对照组,采用全程护理干预的患者纳入观察组。两组患者均干预至出院。比较两组血管迷走神经反射发生率、负面情绪[焦虑自评量表(SAS)、抑郁自评量表(SDS)]、生活质量[诺丁汉健康量表(HNP)]和护理满意度。结果与对照组相比,观察组血管迷走神经反射发生率较低(P<0.05);与对照组相比,观察组干预后的SAS、SDS评分均较低(P<0.05);与对照组相比,观察组干预后躯体活动、疼痛、情感反应、社会生活、睡眠、精力评分较低(P<0.05);与对照组相比,观察组出院时护患沟通、操作水平、病房环境、患者感受评分较高(P<0.05)。结论对行冠状动脉介入诊疗的患者实施全程护理干预能够有效预防和减少血管迷走神经反射的发生率,并利于减轻患者负面情绪,从而促进患者的生活质量和护理满意度的提高。

POTENTIATED EFFECT OF VAGAL STIMULATION AND HORMONAL AGENTS ON PANCREATIC EXOCRINE SECRETION IN DOGS

Chronic experiments were made on eighteen dogs with Thomas pancreatic fistula andgastric fistula. Both in chronic and acute experiments the degenerated right cervical vagusnerve was stimulated by electrical shock and the endogenous secretin and CCK was releasedby means of duodenal acidification (D. A.). The exogenous secretin, atropine and lidocainewere infused to analyse the interrelationship of neurohormones in the pancreatic exocrinesecretion. The results were as follows. In chronic experiments the pancreatic secretory la-tency was shorter and volume larger than that in acute experiments induced by D. A. Thedifference is very significant (P<0.001). Both vagotomy and atropine significantly inhibitedpancreatic secretion induced by D. A. (P<0.01). Lidocaine infused into duodenum inhibitedpancreatic secretion induced by D. A. as well. When vagal stimulation was combined withD. A., either simultaneously or successively, the pancreatic secretion was increased morethan the additive sum obtained by separate action of vagal stimulation and D. A. or secretin.In view of the above--mentioned facts, the author suggests that vagal impulses combined withD. A. or secretin act on the pancreatic exocrine secretion, and that the interaction of nerveand hormones appear to be mutually potentiated.

循经点穴推拿联合经皮耳迷走神经刺激治疗产后功能性消化不良临床研究

目的:观察循经点穴推拿联合经皮耳迷走神经刺激(taVNS)治疗产后功能性消化不良的效果及对胃肠功能的影响。方法:选取188例产后功能性消化不良的患者作为研究对象,按随机数字表法分为常规组、推拿组、taVNS组、联合组各47例。常规组给予常规治疗,推拿组在常规治疗基础上给予循经点穴推拿,taVNS组在常规治疗基础上给予taVNS治疗,联合组在常规治疗基础上给予循经点穴推拿联合taVNS治疗。比较4组临床疗效及不良反应发生情况,比较4组治疗前后中医症状评分、胃肠激素水平及胃电图参数值的变化。结果:治疗后,4组早饱感、餐后饱胀不适、上腹痛、上腹烧灼感中医症状评分均较治疗前下降(P<0.05),推拿组、taVNS组、联合组上述4项评分均低于常规组(P<0.05),联合组上述4项评分均低于常规组、推拿组、taVNS组(P<0.05)。联合组临床疗效总有效率高于常规组、推拿组、taVNS组,差异有统计学意义(P<0.05)。治疗后,4组血清胃泌素和胃动素水平均较治疗前升高(P<0.05),推拿组、taVNS组、联合组均高于常规组(P<0.05),联合组均高于常规组、推拿组、taVNS组(P<0.05)。治疗后,4组餐前、餐后的胃电频率、胃电紊乱百分比均较治疗前降低(P<0.05),正常慢波百分比均较治疗前升高(P<0.05);治疗后,联合组餐前、餐后的胃电频率、胃电紊乱百分比均低于其他3组(P<0.05),正常慢波百分比高于其他3组(P<0.05)。结论:循经点穴推拿联合taVNS治疗产后功能性消化不良有助于缓解症状,增强胃电活动,调节胃肠激素水平,提升疗效。

基于五行辨证理论的耳穴贴压护理对脑血管介入致迷走神经反射的影响

目的:观察基于五行辨证理论的耳穴贴压护理对脑血管介入致迷走神经反射的影响。方法:选取2021年7月—2023年1月广西桂林市中医医院脑病科行脑血管介入治疗的患者80例作为研究对象,随机分为试验组和对照组,各40例。对照组给予常规健康教育及综合心理干预,试验组在对照组基础上给予五行辨证理论的耳穴贴压护理。比较两组迷走神经反射发生率、汉密尔顿焦虑量表(HAMA)和汉密尔顿抑郁量表(HAMD)评分。结果:试验组术后迷走神经反射发生率均低于对照组,差异有统计学意义(P=0.034);干预后,两组HAMA、HAMD评分均降低,试验组低于对照组,差异有统计学意义(P<0.05)。结论:运用基于五行辨证理论的耳穴贴压护理,可以有效减少脑血管介入致迷走神经反射的发生,改善患者负性情绪。

护理干预对冠状动脉介入治疗并发血管迷走神经反射的预防效果研究

分析对冠状动脉介入治疗患者实施护理干预对并发血管迷走神经反射的预防效果。随机抽取2020年10月—2021年10月收治的1200例接受冠状动脉介入治疗的患者为研究对象,将患者分为比照组和试验组,每组各600例。比照组接受常规护理,试验组在常规护理基础上接受针对化护理干预,统计分析两组患者血管迷走神经反射率、抑郁评分、焦虑评分、VAS评分和睡眠质量。研究发现,对冠状动脉介入治疗患者开展针对化护理干预,可降低血管迷走神经反射率,稳定患者情绪,缓解患者疼痛,提高患者睡眠质量。