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Sex differences in heart rate and heart rate variability responses to transcutaneous auricular vagal nerve stimulation in rats. 经皮耳迷走神经刺激对大鼠心率和心率变异性反应的性别差异。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-02-01 Epub Date: 2024-12-13 DOI: 10.1016/j.autneu.2024.103237
Margherita Barbetti, Cristina Ottaviani, Julian F Thayer, Andrea Sgoifo, Luca Carnevali

The identification of reliable biomarkers of transcutaneous auricular vagus nerve stimulation (taVNS) responsiveness is a key challenge both at the clinical and preclinical level. Vagally-mediated heart rate variability (vmHRV), a surrogate measure of cardiac vagal efferent activity, is an ideal candidate. Yet, the effects of taVNS on vmHRV remain inconclusive, likely due to the high degree of heterogeneity in stimulation protocols (e.g., taVNS parameters and side of the ear target), and little consideration of contributing factors such as sex differences. This study investigates sex differences in heart rate and vmHRV responses to different protocols of taVNS in adult rats. Male and female wild-type Groningen rats received sham or active stimulation (6 Hz or 20 Hz, 1 ms, 6 V) on the left or right auricular concha region. ECG signals were recorded before (10 min), during (20 min) and after (10 min) each session in a between-subject design. We found differential side-, frequency- and sex-specific chronotropic responses to taVNS, whereby heart rate decreased and vmHRV indexes increased at 6 Hz in males and at 20 Hz in females. Also, increases in vmHRV were only observed for right-side taVNS. The current findings suggest that biological sex should be considered for fine-tuning regulation of taVNS-induced cardiac responses and provide information regarding the side-specific effects of taVNS on vmHRV. These results will likely guide future rodent research to the choice of the most appropriate stimulation protocol in both sexes for generating information that can be translated into taVNS-related strategies in humans.

确定可靠的经皮耳迷走神经刺激(taVNS)反应性生物标志物是临床和临床前水平的关键挑战。迷走神经介导的心率变异性(vmHRV)是衡量心脏迷走神经传出活动的替代指标,是一个理想的候选指标。然而,taVNS对vmHRV的影响仍然不确定,这可能是由于刺激方案的高度异质性(例如,taVNS参数和侧耳目标),以及对性别差异等影响因素的考虑较少。本研究探讨了不同taVNS方案下成年大鼠心率和vmHRV反应的性别差异。雄性和雌性野生型格罗宁根大鼠分别在左、右耳甲区接受6 Hz或20 Hz, 1 ms, 6 V的假刺激或主动刺激。采用受试者间设计,记录每组前(10分钟)、中(20分钟)和后(10分钟)的心电信号。我们发现taVNS有不同的侧面、频率和性别特异性变时反应,男性在6 Hz时心率下降,vmHRV指数上升,女性在20 Hz时心率下降。此外,vmHRV的增加仅在右侧taVNS中观察到。目前的研究结果表明,taVNS诱导的心脏反应的微调调节应考虑生物性别,并提供有关taVNS对vmHRV的副作用的信息。这些结果可能会指导未来的啮齿动物研究选择最合适的两性刺激方案,以产生可转化为人类tavns相关策略的信息。
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引用次数: 0
A subset of neurons in the paraventricular nucleus of the hypothalamus directly project to liver-related premotor neurons in the ventrolateral medulla 下丘脑室旁核的一部分神经元直接投射到腹外侧髓质中与肝脏相关的前运动神经元。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-02-01 DOI: 10.1016/j.autneu.2024.103222
Lucie D. Desmoulins , Adrien J.R. Molinas , Courtney M. Dugas , Gabrielle L. Williams , Sophie Kamenetsky , Roslyn K. Davis , Andrei V. Derbenev , Andrea Zsombok
Sympathetic circuits including pre-sympathetic neurons in the ventrolateral medulla (VLM) and in the paraventricular nucleus (PVN) of the hypothalamus play an important role in the regulation of hepatic glucose metabolism. Despite the importance of central regulatory pathways, specific information regarding the circuits of liver-related neurons is limited. Here, we tested the hypothesis that PVN neurons are directly connected to spinally-projecting liver-related neurons in the VLM of mice. Pseudorabies virus (PRV) was used to identify liver-related neurons and time-dependent analyses revealed the location and distribution of neurons in the PVN and ventral brainstem. Four days following PRV injection, most liver-related neurons were found in the VLM and consist of both catecholaminergic (CA) and non-CA neurons. Furthermore, in addition to PRV inoculation, a monosynaptic viral tracer was used to identify VLM-projecting PVN neurons to specifically dissect PVN-VLM connections within the liver pathway. Five days following PRV inoculation, our anatomical findings revealed that a small population of liver-related PVN neurons projected to the VLM. In addition, photo-stimulation of axonal projections from SIM1-expressing PVN neurons resulted in evoked excitatory postsynaptic currents in a subset of spinally projecting liver-related neurons in the VLM. In summary, our data demonstrate the existence of monosynaptic, glutamatergic connections between PVN neurons and pre-sympathetic liver-related neurons in the VLM. These new findings regarding the central circuits involved in the sympathetic regulation of the liver provide further information necessary for developing new strategies to improve glucose homeostasis via modulation of the autonomic nerves.
包括腹外侧髓质(VLM)和下丘脑室旁核(PVN)的前交感神经元在内的交感神经回路在调节肝脏葡萄糖代谢中起重要作用。尽管中央调控通路的重要性,具体的信息关于肝相关神经元的电路是有限的。在这里,我们验证了PVN神经元与小鼠VLM中脊柱突出的肝脏相关神经元直接相连的假设。伪狂犬病毒(PRV)用于鉴定肝脏相关神经元,时间依赖性分析揭示了神经元在PVN和腹侧脑干中的位置和分布。注射PRV 4天后,在VLM中发现大多数肝脏相关神经元,包括儿茶酚胺能(CA)和非CA神经元。此外,除了接种PRV外,还使用单突触病毒示踪剂来鉴定vlm投射的PVN神经元,以特异性地解剖肝脏通路内PVN- vlm连接。在PRV接种5天后,我们的解剖结果显示,一小群肝脏相关的PVN神经元投射到VLM。此外,来自表达sim1的PVN神经元的轴突投射的光刺激导致VLM中一部分脊髓投射的肝脏相关神经元的突触后电流被激发。总之,我们的数据表明PVN神经元和VLM中前交感肝脏相关神经元之间存在单突触、谷氨酸能连接。这些关于参与肝脏交感调节的中枢回路的新发现为开发通过调节自主神经来改善葡萄糖稳态的新策略提供了进一步的必要信息。
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引用次数: 0
Paroxysmal sympathetic hyperactivity: A common consequence of traumatic brain injury. 阵发性交感神经亢进:创伤性脑损伤的常见后果。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1016/j.autneu.2024.103238
Fnu Nancy, Aliza Khowaja, Preet Khowaja

Paroxysmal Sympathetic Hyperactivity (PSH) is a challenging and often underrecognized syndrome, commonly arising after a traumatic brain injury (TBI). Characterized by episodic bursts of heightened sympathetic activity, PSH presents with a distinct constellation of symptoms including hypertension, tachycardia, hyperthermia, and diaphoresis. While the exact pathophysiology remains elusive, current evidence suggests that the syndrome results from an imbalance between excitatory and inhibitory neuronal pathways within the central nervous system, leading to dysregulated autonomic responses. The unpredictable nature of PSH episodes can significantly complicate the clinical course of TBI patients, increasing the risk of secondary brain injury and other systemic complications. Management of PSH involves a combination of pharmacological agents, such as beta-blockers, opioids, and sedatives, to modulate sympathetic outflow, alongside non-pharmacological strategies aimed at minimizing environmental triggers. Early recognition and targeted intervention are crucial to improving outcomes. This communication delves into the clinical presentation, underlying mechanisms, and evolving management strategies of PSH, providing insights into its impact on the recovery of TBI patients.

阵发性交感神经过动症(PSH)是一种具有挑战性且常被忽视的综合征,通常发生在创伤性脑损伤(TBI)后。PSH以偶发性交感神经活动增强为特征,表现为一系列明显的症状,包括高血压、心动过速、高热和出汗。虽然确切的病理生理机制仍然难以捉摸,但目前的证据表明,该综合征是由中枢神经系统内兴奋性和抑制性神经元通路之间的不平衡引起的,导致自主神经反应失调。PSH发作的不可预测性会显著复杂化TBI患者的临床病程,增加继发性脑损伤和其他系统性并发症的风险。PSH的管理包括联合使用药物,如-受体阻滞剂、阿片类药物和镇静剂,以调节交感神经流出,以及旨在减少环境触发因素的非药物策略。早期识别和有针对性的干预对改善结果至关重要。本文深入探讨了PSH的临床表现、潜在机制和不断发展的管理策略,为其对TBI患者康复的影响提供了见解。
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引用次数: 0
Abnormal cardiovascular control during exercise: Role of insulin resistance in the brain.
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-01-19 DOI: 10.1016/j.autneu.2025.103239
Juan A Estrada, Amane Hori, Ayumi Fukazawa, Rie Ishizawa, Norio Hotta, Han-Kyul Kim, Scott A Smith, Masaki Mizuno

During exercise circulatory adjustments to meet oxygen demands are mediated by multiple autonomic mechanisms, the skeletal muscle exercise pressor reflex (EPR), the baroreflex (BR), and by feedforward signals from central command neurons in higher brain centers. Insulin resistance in peripheral tissues includes sensitization of skeletal muscle afferents by hyperinsulinemia which is in part responsible for the abnormally heightened EPR function observed in diabetic animal models and patients. However, the role of insulin signaling within the central nervous system (CNS) is receiving increased attention as a potential therapeutic intervention in diseases with underlying insulin resistance. This review will highlight recent advances in our understanding of how insulin resistance induces changes in central signaling. The alterations in central insulin signaling produce aberrant cardiovascular responses to exercise. In particular, we will discuss the role of insulin signaling within the medullary cardiovascular control nuclei. The nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) are key nuclei where insulin has been demonstrated to modulate cardiovascular reflexes. The first locus of integration for the EPR, BR and central command is the NTS which is high in neurons expressing insulin receptors (IRs). The IRs on these neurons are well positioned to modulate cardiovascular responses to exercise. Additionally, the differences in IR density and presence of receptor isoforms enable specificity and diversity of insulin actions within the CNS. Therefore, non-invasive delivery of insulin into the CNS may be an effective means of normalizing cardiovascular responses to exercise in patients with insulin resistance.

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引用次数: 0
Piezo1, but not ATP, is required for mechanotransduction by bladder mucosal afferents in cystitis 膀胱炎患者膀胱粘膜传入的机械传导需要Piezo1,但不需要ATP。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.autneu.2024.103231
Wai Ping Yew, Timothy Hibberd, Nick J. Spencer, Vladimir Zagorodnyuk
Piezo ion channels play a role in bladder sensation, but the sensory afferent subtypes that utilise Piezo channels have not been fully explored. We made single-unit extracellular recordings from mucosal-projecting bladder afferents in guinea pigs with protamine/zymosan-induced cystitis. The Piezo1 agonist, Yoda1, significantly potentiated mechanosensitivity, while its antagonist, Dooku1, abolished this potentiation. The P2 purinoceptor antagonist, PPADS abolished α,β-methylene ATP-induced excitation of mucosal afferents without affecting their mechanical activation or potentiation of mechanosensitivity by Yoda1. The findings suggest Piezo1, but not ATP, is required for mechanotransduction in bladder mucosal afferents in cystitis.
压电离子通道在膀胱感觉中发挥作用,但利用压电离子通道的感觉传入亚型尚未得到充分探索。我们对患有鱼精蛋白/酶酶酶诱导的膀胱炎的豚鼠的粘膜突出膀胱传入事件进行了单细胞外记录。Piezo1激动剂Yoda1显著增强机械敏感性,而其拮抗剂Dooku1则消除这种增强作用。P2嘌呤受体拮抗剂PPADS可消除α,β-亚甲基atp诱导的粘膜传入兴奋,而不影响Yoda1的机械激活或机械敏感性增强。研究结果表明,膀胱炎患者膀胱粘膜传入的机械转导需要Piezo1,而不需要ATP。
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引用次数: 0
Co-occurrence of Loeys-Dietz syndrome with postural orthostatic tachycardia syndrome: A case series Loeys-Dietz综合征合并体位性心动过速综合征:一个病例系列
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.autneu.2024.103220
Michel Boustany , Ali Arvantaj , Kamal R. Chémali
Loeys-Dietz syndrome (LDS) is a connective tissue disorder arising from mutations in the TGF- β signaling pathway. The spectrum of clinical manifestations is broad, and includes vascular, skeletal, and craniofacial abnormalities, along with joint hypermobility. No evidence of postural orthostatic tachycardia syndrome (POTS) in these patients has been reported. We report here a case series of patients with LDS presenting to the autonomic clinic and found to have POTS. Understanding the exact pathophysiology of this association requires further studies. Acknowledging the co-occurrence of these conditions is important to improve outcomes, and managing POTS in LDS patients necessitates an interdisciplinary approach.
Loeys-Dietz综合征(LDS)是由TGF- β信号通路突变引起的结缔组织疾病。临床表现范围广泛,包括血管、骨骼和颅面异常,以及关节活动过度。没有证据表明这些患者有体位性站立性心动过速综合征(POTS)。我们在此报告一例LDS患者到自主神经诊所就诊并发现有POTS。了解这种关联的确切病理生理学需要进一步的研究。认识到这些情况的共同发生对于改善预后很重要,并且管理LDS患者的POTS需要跨学科的方法。
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引用次数: 0
Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour 早期母亲分离和艾司西酞普兰治疗对抑郁样行为大鼠的心血管影响
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.autneu.2024.103223
Luiz Fernando Veríssimo , Fernando Henrique Ferrari Alves , Viviane Batista Estrada , Leonardo Andre da Costa Marques , Karoliny Coelho Andrade , Amanda Monteiro Bonancea , Natália Tavares Okano , Fernando Morgan de Aguiar Corrêa , Gislaine Garcia Pelosi
Depression and cardiovascular diseases are two of the world's major health problems. Escitalopram (ESC) is widely used because of its safety in relation to other drugs in that class; however, it can affect the cardiovascular system. The present study evaluated the cardiovascular parameters of depressive-like male rats and the cardiovascular effects of ESC treatment on that condition. The EMS protocol consisted of separating the litter from the dam for 3 h over 13 days. Animals were anesthetized with tribromoethanol (250 mg/kg, intraperitoneally) and the catheters were inserted into the femoral and into the femoral vein. Depressive-like rats showed an increase in the pressor response to phenylephrine (Emax:depressive = 50.36 ± 2.997 mmHg; non-depressive = 39.51 ± 3.328 mmHg; p < 0.05) and a reduction in the EC50 (depressive = 0.6203 ± 0.03005 μg/kg; non-depressive = 0.7320 ± 0.03519 μg/kg; p < 0.05) with no change in the other cardiovascular parameters. After treatment with ESC, a reduction of intrinsic heart rate was observed in the depressive-like rats (control: 342 ± 6 bpm; ESC: 316 ± 5 bpm; p < 0.05). In addition, ESC treatment increased the bradycardic (control: −97.81 ± 8.3 bpm; ESC: −137.1 ± 12.31 bpm; p = 0.0236; t = 2.502) during the baroreflex response, caused by an increase in cardiac parasympathetic modulation in the heart, in depressive-like rats (p < 0.001). The findings suggest that depressive-like rats showed cardiovascular changes, and that ESC treatment was able to reverse these changes, suggesting that ESC has a good safety profile for depressive patients with cardiovascular disease due to increased parasympathetic modulation.
抑郁症和心血管疾病是世界上两个主要的健康问题。艾司西酞普兰(ESC)因其相对于同类其他药物的安全性而被广泛使用;然而,它会影响心血管系统。本研究评价了抑郁样雄性大鼠的心血管参数及ESC治疗对其心血管的影响。EMS方案包括在13天内将垃圾与水坝分离3小时。动物用三溴乙醇(250 mg/kg,腹腔注射)麻醉,将导管分别插入股静脉和股静脉。抑郁样大鼠对苯肾上腺素的降压反应增加(Emax:抑郁= 50.36±2.997 mmHg;非抑郁= 39.51±3.328 mmHg;p & lt;0.05), EC50降低(抑郁= 0.6203±0.03005 μg/kg;非抑郁性= 0.7320±0.03519 μg/kg;p & lt;0.05),其他心血管参数无变化。经ESC治疗后,观察到抑郁样大鼠的内在心率降低(对照组:342±6 bpm;ESC: 316±5 bpm;p & lt;0.05)。此外,ESC治疗增加了心动过缓(对照组:−97.81±8.3 bpm;ESC:−137.1±12.31 bpm;p = 0.0236;T = 2.502)在压力反射反应期间,由心脏副交感神经调节的增加引起的,在抑郁样大鼠中(p <;0.001)。研究结果表明,抑郁样大鼠表现出心血管变化,ESC治疗能够逆转这些变化,这表明ESC对伴有心血管疾病的抑郁症患者具有良好的安全性,因为副交感神经调节增加。
{"title":"Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour","authors":"Luiz Fernando Veríssimo ,&nbsp;Fernando Henrique Ferrari Alves ,&nbsp;Viviane Batista Estrada ,&nbsp;Leonardo Andre da Costa Marques ,&nbsp;Karoliny Coelho Andrade ,&nbsp;Amanda Monteiro Bonancea ,&nbsp;Natália Tavares Okano ,&nbsp;Fernando Morgan de Aguiar Corrêa ,&nbsp;Gislaine Garcia Pelosi","doi":"10.1016/j.autneu.2024.103223","DOIUrl":"10.1016/j.autneu.2024.103223","url":null,"abstract":"<div><div>Depression and cardiovascular diseases are two of the world's major health problems. Escitalopram (ESC) is widely used because of its safety in relation to other drugs in that class; however, it can affect the cardiovascular system. The present study evaluated the cardiovascular parameters of depressive-like male rats and the cardiovascular effects of ESC treatment on that condition. The EMS protocol consisted of separating the litter from the dam for 3 h over 13 days. Animals were anesthetized with tribromoethanol (250 mg/kg, intraperitoneally) and the catheters were inserted into the femoral and into the femoral vein. Depressive-like rats showed an increase in the pressor response to phenylephrine (E<sub>max:</sub>depressive = 50.36 ± 2.997 mmHg; non-depressive = 39.51 ± 3.328 mmHg; <em>p</em> &lt; 0.05) and a reduction in the EC<sub>50</sub> (depressive = 0.6203 ± 0.03005 μg/kg; non-depressive = 0.7320 ± 0.03519 μg/kg; p &lt; 0.05) with no change in the other cardiovascular parameters. After treatment with ESC, a reduction of intrinsic heart rate was observed in the depressive-like rats (control: 342 ± 6 bpm; ESC: 316 ± 5 bpm; <em>p</em> &lt; 0.05). In addition, ESC treatment increased the bradycardic (control: −97.81 ± 8.3 bpm; ESC: −137.1 ± 12.31 bpm; <em>p</em> = 0.0236; <em>t</em> = 2.502) during the baroreflex response, caused by an increase in cardiac parasympathetic modulation in the heart, in depressive-like rats (<em>p</em> &lt; 0.001). The findings suggest that depressive-like rats showed cardiovascular changes, and that ESC treatment was able to reverse these changes, suggesting that ESC has a good safety profile for depressive patients with cardiovascular disease due to increased parasympathetic modulation.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"Article 103223"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757708","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
Metabolic targets in the Postural Orthostatic Tachycardia Syndrome: A short thematic review 体位性站立性心动过速综合征的代谢目标:一个简短的专题综述。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-12-01 DOI: 10.1016/j.autneu.2024.103232
Alaina C. Glasgow, Joon Young Kim
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic condition hallmarked by orthostatic intolerance and tachycardia in the upright position. POTS impacts approximately 1–3 million people in the U.S. alone, in which the majority of patients are premenopausal women. The etiology of POTS is multi-factorial with three primary clinical subtypes, including neuropathic, hyperadrenergic, and hypovolemic POTS. Recent evidence suggests potential metabolic associations with POTS pathophysiology, particularly involving insulin resistance and abnormal vasoactive gut hormones. This review aims to characterize POTS phenotypes and explore potential metabolic links, focusing on insulin resistance and vasoactive gut hormones. Understanding the metabolic aspects of POTS pathophysiology could provide novel insights into its mechanisms and guide therapeutic approaches.
体位性站立性心动过速综合征(POTS)是一种慢性自主神经疾病,其特征是直立体位不耐受和心动过速。仅在美国,POTS就影响了大约1-3百万人,其中大多数患者是绝经前妇女。POTS的病因是多因素的,主要有三种临床亚型,包括神经性、高肾上腺素能性和低血容量性POTS。最近的证据表明,潜在的代谢与POTS病理生理有关,特别是涉及胰岛素抵抗和异常血管活性肠道激素。这篇综述的目的是表征POTS表型和探索潜在的代谢联系,重点是胰岛素抵抗和血管活性肠道激素。了解POTS病理生理的代谢方面可以为其机制和指导治疗方法提供新的见解。
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引用次数: 0
Distribution and morphology of CGRP-IR axons in flat-mounts of whole male and female mouse atria
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-29 DOI: 10.1016/j.autneu.2024.103221
Kohlton Bendowski, Yuanyuan Zhang, Ariege Bizanti, Duyen Nguyen, Adhithyaa Nair, Jichao Ma, Jin Chen, Zixi Jack Cheng
Due to a lack of anatomical studies utilizing female specimens, it is unclear how the nociceptive innervation of the mouse heart compares between sexes. To address this, flat-mount preparations of the left and right atria of male and female mice were immunohistochemically labeled for calcitonin gene-related peptide (CGRP, a common marker for nociceptive nerves), imaged, and digitally traced in high quality. The results show that 1) A network of CGRP-IR axons densely innervated the right and left atria. Large nerve bundle entry points and regional concentration of CGRP-IR axons were similar in both sexes. 2) The detailed distribution of CGRP-IR bundles and axons were digitized and mapped using Arivis (Zeiss) Vision4D software. The general distribution patterns in male and female mice were comparable to one another. 3) The density of CGRP-IR axons in the sinoatrial (SA) node region (Male: 0.0258 μm/μm2 ± 0.003; Female: 0.0347 μm/μm2 ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm2 ± 0.001; Female: 0.0228 μm/μm2 ± 0.005) were not found to be significantly different. 4) The distance between adjacent varicosities in the auricle (Male: 4.049 μm ± 0.3; Female: 4.241 μm ± 0.34), SA node region (Male: 2.812 μm ± 0.21; Female: 3.352 μm ± 0.29), and AV node region (Male: 2.999 μm ± 0.3; Female: 3.526 μm ± 0.26) were not significantly different between sexes. 5) Likewise, maximum varicosity diameters in the auricle (Male: 0.5356 μm ± 0.04; Female: 0.5274 μm ± 0.03), SA node region (Male: 0.4714 μm ± 0.02; Female: 0.5634 μm ± 0.04), and AV node region (Male: 0.5103 μm ± 0.02; Female: 0.5103 μm ± 0.03) between male and female specimens were similar. Our data shows the comparable nature of the CGRP-IR axons in mouse atria in both sexes. Moreover, this is the first time we employed flat-mount preparations of whole atria to analyze the distribution of CGRP-IR axons in male and female mice.
{"title":"Distribution and morphology of CGRP-IR axons in flat-mounts of whole male and female mouse atria","authors":"Kohlton Bendowski,&nbsp;Yuanyuan Zhang,&nbsp;Ariege Bizanti,&nbsp;Duyen Nguyen,&nbsp;Adhithyaa Nair,&nbsp;Jichao Ma,&nbsp;Jin Chen,&nbsp;Zixi Jack Cheng","doi":"10.1016/j.autneu.2024.103221","DOIUrl":"10.1016/j.autneu.2024.103221","url":null,"abstract":"<div><div>Due to a lack of anatomical studies utilizing female specimens, it is unclear how the nociceptive innervation of the mouse heart compares between sexes. To address this, flat-mount preparations of the left and right atria of male and female mice were immunohistochemically labeled for calcitonin gene-related peptide (CGRP, a common marker for nociceptive nerves), imaged, and digitally traced in high quality. The results show that 1) A network of CGRP-IR axons densely innervated the right and left atria. Large nerve bundle entry points and regional concentration of CGRP-IR axons were similar in both sexes. 2) The detailed distribution of CGRP-IR bundles and axons were digitized and mapped using Arivis (Zeiss) Vision4D software. The general distribution patterns in male and female mice were comparable to one another. 3) The density of CGRP-IR axons in the sinoatrial (SA) node region (Male: 0.0258 μm/μm<sup>2</sup> ± 0.003; Female: 0.0347 μm/μm<sup>2</sup> ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm<sup>2</sup> ± 0.001; Female: 0.0228 μm/μm<sup>2</sup> ± 0.005) were not found to be significantly different. 4) The distance between adjacent varicosities in the auricle (Male: 4.049 μm ± 0.3; Female: 4.241 μm ± 0.34), SA node region (Male: 2.812 μm ± 0.21; Female: 3.352 μm ± 0.29), and AV node region (Male: 2.999 μm ± 0.3; Female: 3.526 μm ± 0.26) were not significantly different between sexes. 5) Likewise, maximum varicosity diameters in the auricle (Male: 0.5356 μm ± 0.04; Female: 0.5274 μm ± 0.03), SA node region (Male: 0.4714 μm ± 0.02; Female: 0.5634 μm ± 0.04), and AV node region (Male: 0.5103 μm ± 0.02; Female: 0.5103 μm ± 0.03) between male and female specimens were similar. Our data shows the comparable nature of the CGRP-IR axons in mouse atria in both sexes. Moreover, this is the first time we employed flat-mount preparations of whole atria to analyze the distribution of CGRP-IR axons in male and female mice.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"258 ","pages":"Article 103221"},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069802","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
Baroreflex activation therapy through electrical carotid sinus stimulation 通过颈动脉窦电刺激激活巴反射疗法。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2024-11-13 DOI: 10.1016/j.autneu.2024.103219
Jens Jordan , Jens Tank , Karsten Heusser , Hannes Reuter
An imbalance between cardiovascular parasympathetic and sympathetic activity towards sympathetic predominance has been implicated in the pathogenesis of treatment-resistant arterial hypertension and heart failure. Arterial baroreceptors control efferent cardiovascular autonomic activity and have, therefore, been recognized as potential treatment targets. Baroreflex activation therapy through electrical carotid sinus stimulation is a device-based approach to modulate cardiovascular autonomic activity. Electrical carotid sinus stimulation lowered blood pressure in various hypertensive animal models and improved cardiac remodeling and survival in preclinical models of heart failure. In human mechanistic profiling studies, electrical carotid sinus stimulation lowered blood pressure through sympathetic inhibition with substantial inter-individual variability. The first-generation device reduced blood pressure in controlled and uncontrolled clinical trials. Controlled clinical trials proving efficacy in blood pressure reduction in patients with hypertension do not exist for the currently available second-generation carotid sinus stimulator. Investigations in heart failure patients showed improved symptoms, quality of life, and natriuretic peptide biomarkers. Electrical carotid sinus stimulation is an interesting technology to modulate cardiovascular autonomic control. However, controlled trials with hard clinical endpoints are required.
心血管副交感神经和交感神经活动失衡,交感神经占主导地位,这与治疗耐受性动脉高血压和心力衰竭的发病机制有关。动脉气压感受器控制着心血管自主神经的传出活动,因此被认为是潜在的治疗目标。通过颈动脉窦电刺激激活巴反射疗法是一种基于设备的调节心血管自律神经活动的方法。颈动脉窦电刺激可降低各种高血压动物模型的血压,改善心衰临床前模型的心脏重塑和存活率。在人体机理分析研究中,颈动脉窦电刺激可通过抑制交感神经降低血压,但个体间差异很大。在对照和非对照临床试验中,第一代设备降低了血压。目前市场上的第二代颈动脉窦刺激器还没有证明对高血压患者有降压疗效的对照临床试验。对心力衰竭患者进行的调查显示,患者的症状、生活质量和钠尿肽生物标志物均有所改善。颈动脉窦电刺激是一种调节心血管自律神经控制的有趣技术。不过,还需要进行具有硬性临床终点的对照试验。
{"title":"Baroreflex activation therapy through electrical carotid sinus stimulation","authors":"Jens Jordan ,&nbsp;Jens Tank ,&nbsp;Karsten Heusser ,&nbsp;Hannes Reuter","doi":"10.1016/j.autneu.2024.103219","DOIUrl":"10.1016/j.autneu.2024.103219","url":null,"abstract":"<div><div>An imbalance between cardiovascular parasympathetic and sympathetic activity towards sympathetic predominance has been implicated in the pathogenesis of treatment-resistant arterial hypertension and heart failure. Arterial baroreceptors control efferent cardiovascular autonomic activity and have, therefore, been recognized as potential treatment targets. Baroreflex activation therapy through electrical carotid sinus stimulation is a device-based approach to modulate cardiovascular autonomic activity. Electrical carotid sinus stimulation lowered blood pressure in various hypertensive animal models and improved cardiac remodeling and survival in preclinical models of heart failure. In human mechanistic profiling studies, electrical carotid sinus stimulation lowered blood pressure through sympathetic inhibition with substantial inter-individual variability. The first-generation device reduced blood pressure in controlled and uncontrolled clinical trials. Controlled clinical trials proving efficacy in blood pressure reduction in patients with hypertension do not exist for the currently available second-generation carotid sinus stimulator. Investigations in heart failure patients showed improved symptoms, quality of life, and natriuretic peptide biomarkers. Electrical carotid sinus stimulation is an interesting technology to modulate cardiovascular autonomic control. However, controlled trials with hard clinical endpoints are required.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"Article 103219"},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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