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The potential of taVNS in attenuating blood-brain barrier damage, promoting angiogenesis and improving impaired cognitive function in a rat model of vascular cognitive impairment and dementia by activating the Wnt7/β-catenin signaling pathway taVNS通过激活Wnt7/β-catenin信号通路,在血管性认知障碍和痴呆大鼠模型中减轻血脑屏障损伤、促进血管生成和改善认知功能受损的潜力。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-10-13 DOI: 10.1016/j.autneu.2025.103353
Rongshan Sun , Hong Li , Meng Wang , Long Yan , Jinglei Jiang , Qidi Liu , Shijun Li , Ying Liang , Yulin Qian , Tao Yu

Background

Studies consistently demonstrate that vascular cognitive impairment and dementia (VCID) onset and progression are associated with diminished activity in the Wnt/β-catenin signaling pathway, crucial for maintaining blood-brain barrier (BBB) integrity and promoting angiogenesis in the central nervous system. Transcutaneous auricular vagal nerve stimulation (taVNS) has shown potential to enhance cognitive function by reducing BBB permeability and stimulating angiogenesis, yet its direct linkage to the Wnt7/β-catenin pathway activation remains uncertain and requires mechanistic validation.

Methods

A rat model of VCID was established by inducing temporary bilateral common carotid artery occlusion (tBCCAO) in rats. Following surgery, rats received daily taVNS treatments for 14 consecutive days (Days 13–26). Cognitive function was assessed on postoperative day 26. Additionally, the hippocampal region was analyzed to detect changes in the Wnt7/β-catenin signaling pathway-related proteins, neuronal injury and apoptosis, angiogenesis, BBB tight junction integrity, and astrocyte activation.

Results

TaVNS treatment resulted in significant cognitive improvements, alongside marked reductions in neuronal damage and apoptosis within the hippocampal CA1 region. It effectively decreased BBB permeability and enhanced angiogenesis. Mechanistically, taVNS suppressed astrocyte activation, promoted a shift from pro-inflammatory (A1) to anti-inflammatory (A2) phenotypes, and consequently upregulated the Wnt7/β-catenin signaling pathway, boosting expression of its downstream targets to foster neuroprotection and vascular repair.

Conclusions

This study confirms that taVNS effectively alleviates neurological damage in VCID by upregulating the Wnt7/β-catenin pathway, potentially through astrocyte phenotypic modulation. These findings underscore taVNS as a promising non-invasive intervention for cognitive deficits in vascular disorders, warranting further clinical investigation.
背景:研究一致表明,血管性认知障碍和痴呆(VCID)的发生和进展与Wnt/β-catenin信号通路活性降低有关,Wnt/β-catenin信号通路对于维持血脑屏障(BBB)完整性和促进中枢神经系统血管生成至关重要。经皮耳迷走神经刺激(taVNS)已显示出通过降低血脑屏障通透性和刺激血管生成来增强认知功能的潜力,但其与Wnt7/β-catenin通路激活的直接联系仍不确定,需要机制验证。方法:通过诱导双侧颈总动脉暂时性闭塞(tBCCAO)建立大鼠VCID模型。手术后,大鼠连续14天(第13-26天)每天接受taVNS治疗。术后第26天评估认知功能。此外,我们还对海马区进行了分析,以检测Wnt7/β-catenin信号通路相关蛋白、神经元损伤和凋亡、血管生成、血脑屏障紧密连接完整性和星形胶质细胞激活的变化。结果:TaVNS治疗可显著改善认知能力,同时显著减少海马CA1区神经元损伤和细胞凋亡。有效降低血脑屏障通透性,促进血管生成。在机制上,taVNS抑制星形胶质细胞活化,促进从促炎(A1)表型向抗炎(A2)表型的转变,从而上调Wnt7/β-catenin信号通路,提高其下游靶点的表达,促进神经保护和血管修复。结论:本研究证实,taVNS通过上调Wnt7/β-catenin通路,可能通过星形细胞表型调节,有效缓解VCID的神经损伤。这些发现强调了taVNS作为一种有希望的非侵入性干预血管疾病认知缺陷的方法,值得进一步的临床研究。
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引用次数: 0
Vericiguat attenuates the dynamic gain of open-loop baroreflex function in a low-frequency range Vericiguat在低频范围内衰减开环气压反射函数的动态增益。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-10-10 DOI: 10.1016/j.autneu.2025.103354
Aimi Yokoi , Toru Kawada , Nana Hiraki , Midori Kakuuchi , Takuya Nishikawa , Masafumi Fukumitsu , Kei Sato , Joe Alexander Jr , Ryou Tanaka , Keita Saku
Vericiguat, a soluble guanylate cyclase stimulator, enhances the production of cyclic guanosine monophosphate through nitric oxide (NO)-dependent and -independent mechanisms. We examined the effects of vericiguat on the open-loop dynamic characteristics of the carotid sinus baroreflex. In anesthetized Wistar–Kyoto rats (n = 8), sympathetic nerve activity (SNA), arterial pressure (AP), and aortic flow were measured while varying carotid sinus pressure (CSP) according to a Gaussian white noise signal with a mean of 120 mmHg and a standard deviation of 20 mmHg. The neural arc transfer function from CSP to SNA, peripheral arc transfer function from SNA to AP, and total arc transfer function from CSP to AP were compared between the baseline conditions and during intravenous administrations of vericiguat (10 μg·kg−1·min−1). Vericiguat treatment reduced the asymptotic dynamic gain in the peripheral arc but not in the neural arc. It also reduced the asymptotic dynamic gain and increased the corner frequency in the total arc. These findings indicate low-frequency-dominant attenuation of dynamic gain, suggesting that vericiguat enhances the negative feedback regulation of vasoconstriction mediated by endogenous NO.
Vericiguat是一种可溶性鸟苷环化酶刺激剂,通过一氧化氮(NO)依赖性和非依赖性机制促进环鸟苷单磷酸的产生。我们检查了vericiguat对颈动脉窦压力反射开环动态特性的影响。麻醉Wistar-Kyoto大鼠(n = 8),测量交感神经活动(SNA)、动脉压(AP)和主动脉流量,同时改变颈动脉窦压(CSP),根据高斯白噪声信号,平均值为120 mmHg,标准差为20 mmHg。比较基线条件和静脉给药(10 μg·kg-1·min-1)时CSP到SNA的神经弧传递函数、SNA到AP的外周弧传递函数和CSP到AP的总弧传递函数。Vericiguat治疗降低了外周弧线的渐近动态增益,但对神经弧线没有影响。减小了渐近动态增益,提高了总弧角频率。这些发现表明动态增益的低频衰减,表明vericiguat增强了内源性NO介导的血管收缩的负反馈调节。
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引用次数: 0
Supportive self-management in postural orthostatic tachycardia syndrome (POTS): A systematic review 体位性站立性心动过速综合征(POTS)的支持性自我管理:系统综述。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-10-06 DOI: 10.1016/j.autneu.2025.103342
Helen Eftekhari , Gemma Pearce , Akansha Singh , Sophie Staniszewska , Kate Seers

Aim

This systematic review aimed to identify components of supportive self-management for postural orthostatic tachycardia syndrome and critically appraise the evidence base.

Design

Systematic review.

Data sources

EMBASE, MEDLINE, CINHAL and charity databases, trial registries and grey literature were searched until December 14th, 2023.

Review methods

The PRISMA guidelines were followed for the search strategy. Data were mapped to the Practical Reviews in Self-management Support taxonomy components and the Middle Range Theory of Self-Care in Chronic Illness. Synthesis and analysis followed guidance on reporting without meta-analysis with summary tables, a logic model, harvest plot, and narrative synthesis.

Results

36 studies were included. Components of supportive self-management were found in 1) lifestyle advice, 2) provision of equipment, and 3) support with adherence. No studies were found on 1) education, 2) psychological well-being, 3) communication needs with health professionals and social support networks, 4) reliable sources of information, 5) training for practical self-management, or clinical action plans, and 5) social support. Studies efficacy’ was hampered by poor research designs, short studies of one day duration, and appropriateness of outcome measures.

Conclusions

Significant gaps were identified requiring further research 1) self-care monitoring activities 2) self-care management activities, 3) provision of education, information and resources 4) addressing psychological well-being and 5) addressing social support. A specific gap exists in the POTS evidence base in nurse led interventions.

Impact

This review evaluates supportive self-management components and identifies key issues with the current evidence base that require addressing to improve and inform the support needs and services of this often disabling, and predominantly female condition. This review is a novel integration of the taxonomy and theory.

Patient and public contribution

Findings were discussed with a postural tachycardia syndrome advisory group, providing important insights into key issues with the studies validity, reliability and generalisability from their perspectives
目的:本系统综述旨在确定体位性心动过速综合征的支持性自我管理的组成部分,并批判性地评估证据基础。设计:系统回顾。数据来源:EMBASE、MEDLINE、CINHAL和charity数据库、试验注册库和灰色文献检索至2023年12月14日。审查方法:搜索策略遵循PRISMA指南。数据被映射到自我管理支持分类成分的实践评论和慢性疾病自我照顾的中程理论。综合和分析遵循报告指南,不使用汇总表、逻辑模型、收获情节和叙事综合进行meta分析。结果:共纳入36项研究。支持性自我管理的组成部分包括:1)生活方式建议,2)提供设备,以及3)坚持支持。没有研究发现1)教育,2)心理健康,3)与卫生专业人员和社会支持网络的沟通需求,4)可靠的信息来源,5)实际自我管理培训或临床行动计划,以及5)社会支持。研究的有效性受到研究设计不佳、研究时间较短(一天)和结果测量的适当性的影响。结论:自我保健监测活动、自我保健管理活动、教育、信息和资源的提供、心理健康的处理和社会支持的处理均存在显著差距,需要进一步研究。在护士主导的干预措施中,POTS证据基础存在具体差距。影响:本综述评估了支持性自我管理的组成部分,并确定了当前证据基础上需要解决的关键问题,以改善和告知这种通常致残的、以女性为主的疾病的支持需求和服务。这篇综述是分类法与理论的新颖结合。患者和公众贡献:研究结果与体位性心动过速综合征咨询小组进行了讨论,从他们的角度对研究的有效性、可靠性和普遍性的关键问题提供了重要的见解。
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引用次数: 0
Sympathetic innervation of the temporomandibular joint modulates local hyperalgesia and IL-6 levels in zymosan-induced inflammatory pain 颞下颌关节交感神经支配调节酵素诱导炎性疼痛的局部痛觉过敏和IL-6水平。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-10-03 DOI: 10.1016/j.autneu.2025.103351
Livia E.C. Corrêa, Tales F.V. Rosin, Fernanda C. Medeiros, Isabela P. Leirão, Eduardo Colombari, Débora S.A. Colombari, Daniel B. Zoccal, Pedro L. Katayama
The temporomandibular joint (TMJ) is critical for essential orofacial functions including chewing and speaking. Chronic pain and dysfunction of the TMJ and its associated structures are classified as temporomandibular disorders (TMDs) and represent a significant public health burden. However, the precise neurobiological mechanisms driving these conditions are still unclear. The autonomic nervous system, in particular the sympathetic nervous system, plays a modulatory role in joint homeostasis, inflammation, and pain. This study investigated the sympathetic innervation of the rat TMJ and its functional role in inflammatory hyperalgesia. We first mapped the origin of sympathetic innervation to the TMJ using retrograde tracing combined with immunostaining. After confirming that the TMJ receives sympathetic input predominantly from the ipsilateral superior cervical ganglion (SCG), we performed unilateral superior cervical ganglionectomy (SCG-X) to assess the impact of sympathetic denervation on zymosan-induced TMJ inflammatory hyperalgesia and local cytokine production. SCG-X procedure significantly exacerbated zymosan-induced mechanical hyperalgesia in the TMJ and markedly increased intra-articular interleukin-6 (IL-6) levels, while tumor necrosis factor-alpha (TNF-alpha) remained unaffected. These results demonstrate that the sympathetic nervous system exerts anti-hyperalgesic and anti-inflammatory roles in the TMJ by modulating local cytokine responses during acute inflammation. This study reveals a previously unidentified neuroimmune mechanism within the TMJ, providing a foundation for developing novel, targeted therapeutic strategies for TMDs.
颞下颌关节(TMJ)对包括咀嚼和说话在内的基本口腔面部功能至关重要。颞下颌关节及其相关结构的慢性疼痛和功能障碍被归类为颞下颌关节疾病(TMDs),是一个重大的公共卫生负担。然而,导致这些情况的确切神经生物学机制仍不清楚。自主神经系统,特别是交感神经系统,在关节内稳态、炎症和疼痛中起调节作用。本研究探讨大鼠颞下颌关节交感神经支配及其在炎性痛觉过敏中的功能作用。我们首先使用逆行示踪结合免疫染色绘制了交感神经支配在TMJ的起源。在确认TMJ主要接受来自同侧颈上神经节(SCG)的交感神经输入后,我们进行了单侧颈上神经节切除术(SCG- x),以评估交感神经去支配对酶酶酶诱导的TMJ炎症性痛觉过敏和局部细胞因子产生的影响。SCG-X手术显著加重了酶生蛋白诱导的TMJ机械痛觉过敏,显著增加了关节内白细胞介素-6 (IL-6)水平,而肿瘤坏死因子- α (tnf - α)未受影响。这些结果表明,在急性炎症时,交感神经系统通过调节局部细胞因子反应在TMJ中发挥抗痛觉和抗炎作用。该研究揭示了TMJ中先前未被发现的神经免疫机制,为开发新的靶向治疗策略提供了基础。
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引用次数: 0
Asymmetric neuroplasticity in stellate ganglia: Unveiling side-specific adaptations to aerobic exercise 星状神经节的不对称神经可塑性:揭示对有氧运动的侧特异性适应。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-09-24 DOI: 10.1016/j.autneu.2025.103338
Fernando Vagner Lobo Ladd , Aliny Antunes Barbosa , Renato Albuquerque de Oliveira Cavalcanti , Larissa Freitas , Reinaldo Barreto Oriá , Ricardo Mario Arida , Mariana Pereira de Melo , Andrzej Loesch , A. Augusto Coppi
The stellate ganglia (SG) are a cluster of sympathetic nerve cells situated in the neck, positioned ventrally to the longus colli muscle and play a vital role in regulating cardiovascular function, especially by modulating cardiac sympathetic nerve activity. While the cardiovascular effects of exercise have been extensively studied, little is known about how physical activity influences the three-dimensional structure of SG neurons. Previous research in Wistar rats demonstrated that aerobic exercise training affects cardiovascular physiology, notably by decreasing heart rate without altering arterial pressures. Remarkably, hypertrophy of SG neurons was observed, suggesting a potential overload-induced adaptation. However, whether these structural changes exhibit side-specific patterns remain unclear. To address this gap, we investigated the effects of moderate-intensity aerobic exercise on SG structure with a focus on body-side asymmetry. Using advanced 3D image analysis and stereological methods, we quantified total neuron count, mean neuronal volume, and overall SG volume in four experimental groups: (1) untrained left SG, (2) trained left SG, (3) untrained right SG, and (4) trained right SG. After 10 weeks of treadmill exercise, trained animals displayed a fourfold increase in neuron count in the right SG compared to the left, an asymmetry absent in untrained animals. Additionally, exercise produced divergent effects on neuronal size: right-side neurons underwent atrophy (1.2-fold decrease), whereas left-side neurons exhibited hypertrophy (1.8-fold increase). In trained animals SG volume was reduced by 1.04- (left SG) or 1.4-fold (right SG) depending on the body side considered. These findings reveal a complex, side-specific neuroplastic response of the autonomic nervous system to physical exercise. The observed asymmetric changes in neuron count, size, and ganglia volume challenge traditional views on exercise-induced neuroplasticity, suggesting a more nuanced and functionally relevant adaptation. This study advances our understanding of autonomic nervous system plasticity in response to exercise and encourages further research into side-specific adaptations, with potential implications for targeted interventions in autonomic disorders, including those impacting cardiovascular function.
星状神经节(SG)是位于颈部的一组交感神经细胞,位于颈长肌腹侧,在调节心血管功能,特别是通过调节心脏交感神经活动方面发挥重要作用。虽然运动对心血管的影响已被广泛研究,但人们对体育活动如何影响SG神经元的三维结构知之甚少。先前对Wistar大鼠的研究表明,有氧运动训练可以影响心血管生理学,特别是在不改变动脉压的情况下降低心率。值得注意的是,观察到SG神经元肥大,表明可能是超负荷诱导的适应。然而,这些结构变化是否表现出侧特异性模式尚不清楚。为了解决这一差距,我们研究了中等强度有氧运动对SG结构的影响,重点是身体侧不对称。采用先进的三维图像分析和立体学方法,我们量化了四个实验组的神经元总数、平均神经元体积和总SG体积:(1)未训练的左SG,(2)训练的左SG,(3)未训练的右SG和(4)训练的右SG。经过10周的跑步机运动后,经过训练的动物右侧SG的神经元数量比左侧增加了4倍,而未经训练的动物则没有这种不对称性。此外,运动对神经元大小产生不同的影响:右侧神经元萎缩(减少1.2倍),而左侧神经元肥大(增加1.8倍)。在受过训练的动物中,根据身体侧面的不同,SG体积减少了1.04倍(左SG)或1.4倍(右SG)。这些发现揭示了自主神经系统对体育锻炼的复杂、侧特异性神经可塑性反应。观察到的神经元数量、大小和神经节体积的不对称变化挑战了运动诱导的神经可塑性的传统观点,提出了一种更细致和功能相关的适应。这项研究促进了我们对运动对自主神经系统可塑性的理解,并鼓励了对侧特异性适应的进一步研究,对自主神经疾病(包括影响心血管功能的疾病)的靶向干预具有潜在的意义。
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引用次数: 0
Autonomic responses in children and adolescents with orthostatic syncope and presyncope: children are not small adults 儿童和青少年直立性晕厥和晕厥前期的自主神经反应:儿童不是小大人。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-09-08 DOI: 10.1016/j.autneu.2025.103340
V.-E.M. Lucci , C.L. Protheroe , C.A. Albaro , M.G. Lloyd , K. Armstrong , S. Franciosi , S. Sanatani , V.E. Claydon
Children and adolescents commonly experience orthostatic intolerance associated with impaired participation and quality of life. We aimed to characterize autonomic responses to provoked presyncope in children with recurrent presyncope/syncope and healthy adolescents.
We determined orthostatic tolerance (OT, time to presyncope [mins]) in 36 pediatric patients (age 15 ± 3 yrs., 26 female) with recurrent presyncope/syncope, and 17 asymptomatic controls (age 13 ± 3 yrs., 8 female), using a tilt test with graded lower body negative pressure. Cardiovascular parameters, forearm vascular resistance (FVR), mean middle cerebral artery velocity (MCAvmean), and breath-by-breath end tidal gases were continuously monitored. Responses to the Valsalva maneuver (VM), cerebral autoregulation, and cerebral reactivity to carbon dioxide were also determined.
OT was similar in pediatric patients (21 ± 1.5 min) and controls (20 ± 2.0 min, p = 0.74), but smaller than adult reference values (33.8 ± 0.8 min, p < 0.01). Tilting decreased systolic arterial pressure in pediatric patients (p = 0.009), but not pediatric controls (p = 0.12). Tilting decreased MCAvmean (p = 0.002) in pediatric patients, with impairments in cerebral autoregulation (p = 0.02) that were negatively correlated with OT (r = −0.322; p = 0.024). Both pediatric patients (+48.9 ± 8.0 %) and controls (+36.7 ± 14.7 %) had small FVR responses compared to adult reference data (+100 ± 12 %, p < 0.01). Blood pressure responses to the VM were abnormal in pediatric patients, with a lower nadir in mean arterial pressure (81.7 ± 2.0 mmHg) compared to pediatric controls (94.0 ± 2.8 mmHg, p = 0.001).
Pediatric patients with recurrent presyncope/syncope had impaired orthostatic cardiovascular and autoregulatory responses compared to pediatric controls. Sympathetically-mediated responses were small in children, underscoring the need for pediatric-specific standards for orthostatic cardiovascular control, and treatments targeting enhancement of vascular resistance in children with syncope.
儿童和青少年通常经历与参与和生活质量受损相关的直立性不耐受。我们的目的是表征复发性晕厥/晕厥前症儿童和健康青少年对诱发性晕厥前症的自主神经反应。我们测定了36例儿童患者(年龄15±3岁)的直立耐受性(OT,到晕厥前的时间[分钟])。26例女性)伴有复发性晕厥前期/晕厥,对照组17例(年龄13±3岁)。(8名女性),采用倾斜试验,下体负压分级。连续监测心血管参数、前臂血管阻力(FVR)、平均大脑中动脉流速(MCAvmean)和逐呼吸末潮气。对Valsalva动作(VM)的反应、大脑自动调节和大脑对二氧化碳的反应也进行了测定。儿科患者的OT(21±1.5 min)与对照组(20±2.0 min, p = 0.74)相似,但小于成人参考值(33.8±0.8 min, p平均值(p = 0.002),脑自动调节功能障碍(p = 0.02)与OT呈负相关(r = -0.322; p = 0.024)。与成人参考数据相比,儿童患者(+48.9±8.0 %)和对照组(+36.7±14.7%)的FVR反应较小(+100±12%,p
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引用次数: 0
Lower urinary tract dysfunction reported in autonomic disorders 自主神经紊乱中下尿路功能障碍的报道。
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-09-03 DOI: 10.1016/j.autneu.2025.103341
Ekawat Vichayanrat , Shiwen Koay , Claire Hentzen , Sarah Wright , Amit Batla , Sara Simeoni , Valeria Iodice , Jalesh N. Panicker
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引用次数: 0
Neurogastroenterology: Current insights into gastrointestinal innervation in health and disease 神经胃肠病学:健康和疾病中胃肠神经支配的最新见解
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-08-29 DOI: 10.1016/j.autneu.2025.103339
Tomas Chmelir , Dagmar Jarkovska , Shashank Pandey , Magdalena Chottova Dvorakova
Neurogastroenterology, a rapidly evolving field, investigates the intricate interactions between the nervous system and the organs of the gastrointestinal tract. This review offers a comprehensive summary of innervation of the gastrointestinal tract, focusing on both extrinsic and intrinsic components. Extrinsic innervation involves the autonomic nervous system, with sympathetic and parasympathetic fibers controlling various digestive functions, while intrinsic innervation, represented by the enteric nervous system, operates largely independently, orchestrating complex processes such as motility, secretion, and immune responses. Recent advances highlight the crucial role of the enteric nervous system, often referred to as the second brain, in maintaining gastrointestinal health and its involvement in various pathologies. The text also provides a basic overview of the pathophysiology of achalasia, Chagas disease, gastroesophageal reflux disease, gastroparesis, diabetic gastroenteropathy, irritable bowel syndrome, chronic intestinal pseudo-obstruction, and Hirschsprung's disease, which are conditions in which innervation of the gastrointestinal tract is more or less affected. The insights provided could pave the way for new interventions, offering hope for patients suffering from related conditions.
神经胃肠病学是一个快速发展的领域,研究神经系统和胃肠道器官之间复杂的相互作用。这篇综述提供了胃肠道神经支配的综合总结,重点是外在和内在成分。外神经支配涉及自主神经系统,由交感和副交感神经纤维控制各种消化功能,而以肠神经系统为代表的内在神经支配在很大程度上独立运作,协调运动、分泌和免疫反应等复杂过程。最近的进展强调了肠神经系统的关键作用,通常被称为第二大脑,在维持胃肠道健康及其参与各种病理。文本还提供了贲门失弛缓症,恰加斯病,胃食管反流病,胃轻瘫,糖尿病胃肠炎,肠易激综合征,慢性肠假性梗阻,和先天性巨结肠病的病理生理学的基本概述,这是条件下,其中胃肠道的神经支配或多或少受到影响。所提供的见解可以为新的干预措施铺平道路,为患有相关疾病的患者带来希望。
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引用次数: 0
Sacral neuromodulation for low urinary tract dysfunction: overview and mechanisms of action 骶神经调节治疗低尿路功能障碍:综述和作用机制
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-08-19 DOI: 10.1016/j.autneu.2025.103337
Pierre-Luc Dequirez , Stefan De Wachter , Xavier Biardeau

Objectives

Sacral neuromodulation (SNM) is widely used since the 1990's for overactive bladder (OAB) and non-obstructive urinary retention (NOUR) with good clinical results. Though, its mechanisms of action are not fully elucidated.

Materials and methods

This narrative review intends to explore the various hypotheses of mechanisms of action in SNM, and to propose a theoretical model of action based on the current literature.

Results

SNM may modulate afferent signaling primarily through sub-sensory activation of pelvic floor muscles, which in turn may generate afferent input transmitted via the spinal cord to supraspinal structures, rather than through direct afferent neural stimulation. SNM may restore the balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) by decreasing activity in the anterior cingulate cortex and increasing activity in the median prefrontal cortex. SNM may also modulate the activity of the limbic system (cingulate cortex, insula), that is related to emotions and is frequently dysregulated in Fowler's syndrome – a specific NOUR entity, and patients with OAB. In NOUR, SNM may restore the periaqueductal gray activity through a diminution of excessive inhibitory afferent messages, particularly through modification of the activity of the median prefrontal cortex. Finally, sacral neuromodulation (SNM) may influence neural plasticity at the peripheral, spinal, and/or supraspinal levels; however, the underlying mechanisms and specific neurophysiological changes remain incompletely understood.

Conclusion

While our understanding of the mechanisms of action of SNM is still evolving, emerging data point toward a multifaceted process involving modulation of peripheral afferent input, spinal processing, and supraspinal structures - including those involved in sensorimotor integration, emotional regulation, and autonomic balance.
目的骶神经调节(SNM)自20世纪90年代以来广泛应用于膀胱过动症(OAB)和非梗阻性尿潴留(NOUR)的治疗,取得了良好的临床效果。然而,其作用机制尚未完全阐明。材料与方法本文旨在探讨SNM中作用机制的各种假设,并在现有文献的基础上提出一个作用的理论模型。结果snm可能主要通过骨盆底肌的亚感觉激活来调节传入信号,而骨盆底肌的亚感觉激活可能产生经脊髓传递到棘上结构的传入输入,而不是通过直接的传入神经刺激来调节传入信号。SNM可能通过减少前扣带皮层的活动和增加正中前额皮质的活动来恢复交感神经系统(SNS)和副交感神经系统(PSNS)之间的平衡。SNM也可能调节边缘系统(扣带皮层、脑岛)的活动,这与情绪有关,在Fowler综合征(一种特殊的NOUR实体)和OAB患者中经常失调。在NOUR中,SNM可能通过减少过度抑制性传入信息来恢复导水管周围的灰色活动,特别是通过改变正中前额皮质的活动。最后,骶神经调节(SNM)可能影响周围、脊柱和/或脊柱上水平的神经可塑性;然而,潜在的机制和特定的神经生理变化仍然不完全清楚。虽然我们对SNM作用机制的理解仍在不断发展,但新出现的数据指向一个涉及外周传入输入、脊髓加工和棘上结构(包括那些涉及感觉运动整合、情绪调节和自主神经平衡的结构)调节的多方面过程。
{"title":"Sacral neuromodulation for low urinary tract dysfunction: overview and mechanisms of action","authors":"Pierre-Luc Dequirez ,&nbsp;Stefan De Wachter ,&nbsp;Xavier Biardeau","doi":"10.1016/j.autneu.2025.103337","DOIUrl":"10.1016/j.autneu.2025.103337","url":null,"abstract":"<div><h3>Objectives</h3><div>Sacral neuromodulation (SNM) is widely used since the 1990's for overactive bladder (OAB) and non-obstructive urinary retention (NOUR) with good clinical results. Though, its mechanisms of action are not fully elucidated.</div></div><div><h3>Materials and methods</h3><div>This narrative review intends to explore the various hypotheses of mechanisms of action in SNM, and to propose a theoretical model of action based on the current literature.</div></div><div><h3>Results</h3><div>SNM may modulate afferent signaling primarily through sub-sensory activation of pelvic floor muscles, which in turn may generate afferent input transmitted via the spinal cord to supraspinal structures, rather than through direct afferent neural stimulation. SNM may restore the balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) by decreasing activity in the anterior cingulate cortex and increasing activity in the median prefrontal cortex. SNM may also modulate the activity of the limbic system (cingulate cortex, insula), that is related to emotions and is frequently dysregulated in Fowler's syndrome – a specific NOUR entity, and patients with OAB. In NOUR, SNM may restore the periaqueductal gray activity through a diminution of excessive inhibitory afferent messages, particularly through modification of the activity of the median prefrontal cortex. Finally, sacral neuromodulation (SNM) may influence neural plasticity at the peripheral, spinal, and/or supraspinal levels; however, the underlying mechanisms and specific neurophysiological changes remain incompletely understood.</div></div><div><h3>Conclusion</h3><div>While our understanding of the mechanisms of action of SNM is still evolving, emerging data point toward a multifaceted process involving modulation of peripheral afferent input, spinal processing, and supraspinal structures - including those involved in sensorimotor integration, emotional regulation, and autonomic balance.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103337"},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ex vivo calcium imaging of sympathetic neurons in intact mouse stellate ganglia 完整小鼠星状神经节交感神经元的离体钙成像
IF 3.3 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-08-11 DOI: 10.1016/j.autneu.2025.103336
Arianna Scalco , Nathan Balthazor , Beth A. Habecker
Sympathetic hyperactivity is a common feature of cardiovascular diseases including hypertension, and sympathetic neurons are hyperactive after a week of angiotensin II (AngII) hypertension. Nerve firing increases intracellular Ca2+ and we wanted to develop a Ca2+ imaging method to quantify activity across many neurons at once. Here we describe a method for ex vivo Ca2+ imaging in intact mouse stellate ganglia. We imaged ganglia from control and AngII (700 ng/min/Kg) hypertensive mice to determine if we could identify Ca2+ parameters that reflected hyperactivity. We expressed GCaMP6s in tyrosine hydroxylase (TH)-positive neurons (THGCaMP6s). Male and female THGCaMP6s mice 17–25 weeks old were used. Images were obtained under baseline conditions, after stimulation with nicotine (10 μM), and after stimulation with potassium chloride (KCl, 40 mM) as a positive control for GCaMP6s expression. Differential fluorescence responses were quantified using an open-source MATLAB processing tool. An additional MATLAB script was composed to analyze and characterize features of the fluorescent responses. The peak Ca2+ response after nicotine treatment trended higher in left but not right stellates from AngII-treated mice, and the distribution of peak responses differed significantly in left ganglia. Decay times were similar in all groups. We compared the peak Ca2+ response after nicotine treatment vs. KCl and found altered frequency distribution of nicotine: KCl responses in left but not right stellates from AngII mice, raising the possibility of selective modulation of cholinergic responses. Calcium imaging allowed simultaneous analysis of multiple cells within ganglia, but did not recapitulate the bilateral hyperactivity identified by electrophysiology.
交感神经过度活跃是包括高血压在内的心血管疾病的共同特征,在血管紧张素II (AngII)高血压一周后交感神经过度活跃。神经放电增加细胞内Ca2+,我们想开发一种Ca2+成像方法来量化许多神经元的活动。在这里,我们描述了一种完整的小鼠星状神经节的离体Ca2+成像方法。我们对对照和AngII (700 ng/min/Kg)高血压小鼠的神经节进行成像,以确定我们是否可以识别反映多动症的Ca2+参数。我们在酪氨酸羟化酶(TH)阳性神经元(THGCaMP6s)中表达GCaMP6s。选取17-25周龄的雄性和雌性THGCaMP6s小鼠。分别在基线条件下、尼古丁(10 μM)刺激后和氯化钾(KCl, 40 mM)刺激后获得GCaMP6s表达的图像。差分荧光响应使用开源MATLAB处理工具进行量化。另外编写了MATLAB脚本来分析和表征荧光响应的特征。尼古丁处理后,左星状核的Ca2+反应峰升高,而右星状核的Ca2+反应峰不升高,且左神经节的Ca2+反应峰分布差异显著。各组的衰变时间相似。我们比较了尼古丁治疗与KCl治疗后的Ca2+峰值反应,发现尼古丁的频率分布发生了变化:KCl反应在AngII小鼠的左星状细胞中,而不是在右星状细胞中,这增加了选择性调节胆碱能反应的可能性。钙显像可以同时分析神经节内的多个细胞,但不能概括电生理学鉴定的双侧过度活跃。
{"title":"Ex vivo calcium imaging of sympathetic neurons in intact mouse stellate ganglia","authors":"Arianna Scalco ,&nbsp;Nathan Balthazor ,&nbsp;Beth A. Habecker","doi":"10.1016/j.autneu.2025.103336","DOIUrl":"10.1016/j.autneu.2025.103336","url":null,"abstract":"<div><div>Sympathetic hyperactivity is a common feature of cardiovascular diseases including hypertension, and sympathetic neurons are hyperactive after a week of angiotensin II (AngII) hypertension. Nerve firing increases intracellular Ca<sup>2+</sup> and we wanted to develop a Ca<sup>2+</sup> imaging method to quantify activity across many neurons at once. Here we describe a method for ex vivo Ca<sup>2+</sup> imaging in intact mouse stellate ganglia. We imaged ganglia from control and AngII (700 ng/min/Kg) hypertensive mice to determine if we could identify Ca<sup>2+</sup> parameters that reflected hyperactivity. We expressed GCaMP6s in tyrosine hydroxylase (TH)-positive neurons (TH<sup>GCaMP6s</sup>). Male and female TH<sup>GCaMP6s</sup> mice 17–25 weeks old were used. Images were obtained under baseline conditions, after stimulation with nicotine (10 μM), and after stimulation with potassium chloride (KCl, 40 mM) as a positive control for GCaMP6s expression. Differential fluorescence responses were quantified using an open-source MATLAB processing tool. An additional MATLAB script was composed to analyze and characterize features of the fluorescent responses. The peak Ca<sup>2+</sup> response after nicotine treatment trended higher in left but not right stellates from AngII-treated mice, and the distribution of peak responses differed significantly in left ganglia. Decay times were similar in all groups. We compared the peak Ca<sup>2+</sup> response after nicotine treatment vs. KCl and found altered frequency distribution of nicotine: KCl responses in left but not right stellates from AngII mice, raising the possibility of selective modulation of cholinergic responses. Calcium imaging allowed simultaneous analysis of multiple cells within ganglia, but did not recapitulate the bilateral hyperactivity identified by electrophysiology.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103336"},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Autonomic Neuroscience-Basic & Clinical
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