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Modulation of the expression of connexins 37, 40, and 43 in endothelial cells in a culture 培养液中内皮细胞中连接蛋白 37、40 和 43 的表达调控
Pub Date : 2024-03-15 DOI: 10.3389/fnetp.2024.1199198
Wenqing Zhuang, Nicholas Mitrou, Steve Kulak, W. Cupples, B. Braam
Connexin (Cx) 37, 40, and 43 are implicated in vascular function, specifically in the electrical coupling of endothelial cells and vascular smooth-muscle cells. In the present study, we investigated whether factors implicated in vascular dysfunction can modulate the gene expression of Cx37, Cx40, and Cx43 and whether this is associated with changes in endothelial layer barrier function in human microvascular endothelial cells (HMEC-1). First, HMEC-1 were subjected to stimuli for 4 and 8 h. We tested their responses to DETA-NONOate, H2O2, high glucose, and angiotensin II, none of which relevantly affected the transcription of the connexin genes. Next, we tested inflammatory factors IL-6, interferon gamma (IFNγ), and TNFα. IFNγ (10 ng/mL) consistently induced Cx40 expression at 4 and 8 h to 10–20-fold when corrected for the control. TNFα and IL-6 resulted in small but significant depressions of Cx37 expression at 4 h. Two JAK inhibitors, epigallocatechin-3-gallate (EGCG) (100–250 μM) and AG490 (100–250 μM), dose-dependently inhibited the induction of Cx40 expression by IFNγ. Subsequently, HMEC-1 were subjected to 10 ng/mL IFNγ for 60 h, and intercellular and transcellular impedance was monitored by electric cell-substrate impedance sensing (ECIS). In response to IFNγ, junctional-barrier impedance increased more than cellular-barrier impedance; this was prevented by AG490 (5 μM). In conclusion, IFNγ can strongly induce Cx40 expression and modify the barrier properties of the endothelial cell membrane through the JAK/STAT pathway. Moreover, the Cx37, Cx40, and Cx43 expression in endothelial cells is stable and, apart from IFNγ, not affected by a number of factors implicated in endothelial dysfunction and vascular diseases.
连接蛋白(Cx)37、40 和 43 与血管功能有关,特别是与内皮细胞和血管平滑肌细胞的电耦合有关。在本研究中,我们探讨了与血管功能障碍有关的因素是否能调节 Cx37、Cx40 和 Cx43 的基因表达,以及这是否与人微血管内皮细胞(HMEC-1)内皮层屏障功能的变化有关。我们测试了它们对 DETA-NONOate、H2O2、高血糖和血管紧张素 II 的反应,这些刺激都不会影响连接蛋白基因的转录。接下来,我们检测了炎症因子 IL-6、γ 干扰素(IFNγ)和 TNFα。IFNγ(10纳克/毫升)在4小时和8小时内持续诱导Cx40的表达,经对照校正后达到10-20倍。两种 JAK 抑制剂--表没食子儿茶素-3-没食子酸酯(EGCG)(100-250 μM)和 AG490(100-250 μM)--剂量依赖性地抑制了 IFNγ 诱导的 Cx40 表达。随后,HMEC-1 在 10 ng/mL IFNγ 作用 60 小时,并通过电细胞-基底阻抗传感(ECIS)监测细胞间和跨细胞阻抗。在 IFNγ 的作用下,连接屏障阻抗的增加大于细胞屏障阻抗的增加;AG490(5 μM)可阻止这种增加。总之,IFNγ 能强烈诱导 Cx40 的表达,并通过 JAK/STAT 途径改变内皮细胞膜的屏障特性。此外,Cx37、Cx40 和 Cx43 在内皮细胞中的表达是稳定的,除 IFNγ 外,不受一些与内皮功能障碍和血管疾病有关的因素的影响。
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引用次数: 0
Emerging wearable technologies for multisystem monitoring and treatment of Parkinson’s disease: a narrative review 用于帕金森病多系统监控和治疗的新兴可穿戴技术:综述
Pub Date : 2024-02-13 DOI: 10.3389/fnetp.2024.1354211
Yasmine M. Kehnemouyi, Todd P. Coleman, Peter A. Tass
Parkinson’s disease (PD) is a chronic movement disorder characterized by a variety of motor and nonmotor comorbidities, including cognitive impairment, gastrointestinal (GI) dysfunction, and autonomic/sleep disturbances. Symptoms typically fluctuate with different settings and environmental factors and thus need to be consistently monitored. Current methods, however, rely on infrequent rating scales performed in clinic. The advent of wearable technologies presents a new avenue to track objective measures of PD comorbidities longitudinally and more frequently. This narrative review discusses and proposes emerging wearable technologies that can monitor manifestations of motor, cognitive, GI, and autonomic/sleep comorbidities throughout the daily lives of PD individuals. This can provide more wholistic insight into real-time physiological versus pathological function with the potential to better assess treatments during clinical trials and allow physicians to optimize treatment regimens. Additionally, this narrative review briefly examines novel applications of wearables as therapy for PD patients.
帕金森病(Parkinson's disease,PD)是一种慢性运动障碍疾病,以各种运动和非运动并发症为特征,包括认知障碍、胃肠道(GI)功能障碍和自主神经/睡眠障碍。症状通常会随不同的环境和环境因素而波动,因此需要持续监测。然而,目前的方法依赖于在诊所进行的不频繁的评分量表。可穿戴技术的出现为纵向、更频繁地追踪帕金森病并发症的客观指标提供了一条新途径。本综述讨论并提出了一些新兴的可穿戴技术,这些技术可以在帕金森病患者的日常生活中监测运动、认知、消化道和自主神经/睡眠合并症的表现。这可以更全面地了解实时生理功能与病理功能,从而在临床试验期间更好地评估治疗方法,并让医生优化治疗方案。此外,本综述还简要探讨了可穿戴设备作为帕金森病患者治疗方法的新型应用。
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引用次数: 0
Emerging wearable technologies for multisystem monitoring and treatment of Parkinson’s disease: a narrative review 用于帕金森病多系统监控和治疗的新兴可穿戴技术:综述
Pub Date : 2024-02-13 DOI: 10.3389/fnetp.2024.1354211
Yasmine M. Kehnemouyi, Todd P. Coleman, Peter A. Tass
Parkinson’s disease (PD) is a chronic movement disorder characterized by a variety of motor and nonmotor comorbidities, including cognitive impairment, gastrointestinal (GI) dysfunction, and autonomic/sleep disturbances. Symptoms typically fluctuate with different settings and environmental factors and thus need to be consistently monitored. Current methods, however, rely on infrequent rating scales performed in clinic. The advent of wearable technologies presents a new avenue to track objective measures of PD comorbidities longitudinally and more frequently. This narrative review discusses and proposes emerging wearable technologies that can monitor manifestations of motor, cognitive, GI, and autonomic/sleep comorbidities throughout the daily lives of PD individuals. This can provide more wholistic insight into real-time physiological versus pathological function with the potential to better assess treatments during clinical trials and allow physicians to optimize treatment regimens. Additionally, this narrative review briefly examines novel applications of wearables as therapy for PD patients.
帕金森病(Parkinson's disease,PD)是一种慢性运动障碍疾病,以各种运动和非运动并发症为特征,包括认知障碍、胃肠道(GI)功能障碍和自主神经/睡眠障碍。症状通常会随不同的环境和环境因素而波动,因此需要持续监测。然而,目前的方法依赖于在诊所进行的不频繁的评分量表。可穿戴技术的出现为纵向、更频繁地追踪帕金森病并发症的客观指标提供了一条新途径。本综述讨论并提出了一些新兴的可穿戴技术,这些技术可以在帕金森病患者的日常生活中监测运动、认知、消化道和自主神经/睡眠合并症的表现。这可以更全面地了解实时生理功能与病理功能,从而在临床试验期间更好地评估治疗方法,并让医生优化治疗方案。此外,本综述还简要探讨了可穿戴设备作为帕金森病患者治疗方法的新型应用。
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引用次数: 0
Astrocytes as critical players of the fine balance between inhibition and excitation in the brain: spreading depolarization as a mechanism to curb epileptic activity 星形胶质细胞是大脑抑制与兴奋之间微妙平衡的关键参与者:扩散去极化是抑制癫痫活动的一种机制
Pub Date : 2024-02-09 DOI: 10.3389/fnetp.2024.1360297
Rune Enger, Kjell Heuser
Spreading depolarizations (SD) are slow waves of complete depolarization of brain tissue followed by neuronal silencing that may play a role in seizure termination. Even though SD was first discovered in the context of epilepsy research, the link between SD and epileptic activity remains understudied. Both seizures and SD share fundamental pathophysiological features, and recent evidence highlights the frequent occurrence of SD in experimental seizure models. Human data on co-occurring seizures and SD are limited but suggestive. This mini-review addresses possible roles of SD during epileptiform activity, shedding light on SD as a potential mechanism for terminating epileptiform activity. A common denominator for many forms of epilepsy is reactive astrogliosis, a process characterized by morphological and functional changes to astrocytes. Data suggest that SD mechanisms are potentially perturbed in reactive astrogliosis and we propose that this may affect seizure pathophysiology.
扩展性去极化(SD)是脑组织完全去极化的慢波,随后神经元沉默,可能在癫痫发作终止中发挥作用。尽管 SD 是在癫痫研究中首次发现的,但 SD 与癫痫活动之间的联系仍未得到充分研究。癫痫发作和 SD 具有共同的基本病理生理学特征,最近的证据表明 SD 在实验性癫痫发作模型中频繁出现。有关癫痫发作和 SD 同时存在的人类数据虽然有限,但却具有暗示性。这篇小型综述探讨了 SD 在癫痫样活动中可能发挥的作用,并阐明了 SD 作为终止癫痫样活动的潜在机制。反应性星形胶质细胞增多症是多种形式癫痫的共同特征,这一过程以星形胶质细胞的形态和功能变化为特征。数据表明,反应性星形胶质细胞增多症可能会扰乱 SD 机制,我们认为这可能会影响癫痫发作的病理生理学。
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引用次数: 0
Astrocytes as critical players of the fine balance between inhibition and excitation in the brain: spreading depolarization as a mechanism to curb epileptic activity 星形胶质细胞是大脑抑制与兴奋之间微妙平衡的关键参与者:扩散去极化是抑制癫痫活动的一种机制
Pub Date : 2024-02-09 DOI: 10.3389/fnetp.2024.1360297
Rune Enger, Kjell Heuser
Spreading depolarizations (SD) are slow waves of complete depolarization of brain tissue followed by neuronal silencing that may play a role in seizure termination. Even though SD was first discovered in the context of epilepsy research, the link between SD and epileptic activity remains understudied. Both seizures and SD share fundamental pathophysiological features, and recent evidence highlights the frequent occurrence of SD in experimental seizure models. Human data on co-occurring seizures and SD are limited but suggestive. This mini-review addresses possible roles of SD during epileptiform activity, shedding light on SD as a potential mechanism for terminating epileptiform activity. A common denominator for many forms of epilepsy is reactive astrogliosis, a process characterized by morphological and functional changes to astrocytes. Data suggest that SD mechanisms are potentially perturbed in reactive astrogliosis and we propose that this may affect seizure pathophysiology.
扩展性去极化(SD)是脑组织完全去极化的慢波,随后神经元沉默,可能在癫痫发作终止中发挥作用。尽管 SD 是在癫痫研究中首次发现的,但 SD 与癫痫活动之间的联系仍未得到充分研究。癫痫发作和 SD 具有共同的基本病理生理学特征,最近的证据表明 SD 在实验性癫痫发作模型中频繁出现。有关癫痫发作和 SD 同时存在的人类数据虽然有限,但却具有暗示性。这篇小型综述探讨了 SD 在癫痫样活动中可能发挥的作用,并阐明了 SD 作为终止癫痫样活动的潜在机制。反应性星形胶质细胞增多症是多种形式癫痫的共同特征,这一过程以星形胶质细胞的形态和功能变化为特征。数据表明,反应性星形胶质细胞增多症可能会扰乱 SD 机制,我们认为这可能会影响癫痫发作的病理生理学。
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引用次数: 0
Feedback control of collective dynamics in an oscillator population with time-dependent connectivity 具有时间相关性的振荡器群体集体动力学的反馈控制
Pub Date : 2024-02-02 DOI: 10.3389/fnetp.2024.1358146
Michael Rosenblum
We present a numerical study of pulsatile feedback-based control of synchrony level in a highly-interconnected oscillatory network. We focus on a nontrivial case when the system is close to the synchronization transition point and exhibits collective rhythm with strong amplitude modulation. We pay special attention to technical but essential steps like causal real-time extraction of the signal of interest from a noisy measurement and estimation of instantaneous phase and amplitude. The feedback loop’s parameters are tuned automatically to suppress synchrony. Though the study is motivated by neuroscience, the results are relevant to controlling oscillatory activity in ensembles of various natures and, thus, to the rapidly developing field of network physiology.
我们对高度互联振荡网络中基于脉冲反馈的同步水平控制进行了数值研究。我们将重点放在系统接近同步转换点并表现出具有强振幅调制的集体节奏的非难情况上。我们特别关注一些技术性但必不可少的步骤,如从噪声测量中实时提取相关信号的因果关系,以及估计瞬时相位和振幅。反馈回路的参数会自动调整,以抑制同步性。虽然这项研究的动机来自神经科学,但其结果与控制各种性质的集合体中的振荡活动相关,因此也与快速发展的网络生理学领域相关。
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引用次数: 0
Feedback control of collective dynamics in an oscillator population with time-dependent connectivity 具有时间相关性的振荡器群体集体动力学的反馈控制
Pub Date : 2024-02-02 DOI: 10.3389/fnetp.2024.1358146
Michael Rosenblum
We present a numerical study of pulsatile feedback-based control of synchrony level in a highly-interconnected oscillatory network. We focus on a nontrivial case when the system is close to the synchronization transition point and exhibits collective rhythm with strong amplitude modulation. We pay special attention to technical but essential steps like causal real-time extraction of the signal of interest from a noisy measurement and estimation of instantaneous phase and amplitude. The feedback loop’s parameters are tuned automatically to suppress synchrony. Though the study is motivated by neuroscience, the results are relevant to controlling oscillatory activity in ensembles of various natures and, thus, to the rapidly developing field of network physiology.
我们对高度互联振荡网络中基于脉冲反馈的同步水平控制进行了数值研究。我们将重点放在系统接近同步转换点并表现出具有强振幅调制的集体节奏的非难情况上。我们特别关注一些技术性但必不可少的步骤,如从噪声测量中实时提取相关信号的因果关系,以及估计瞬时相位和振幅。反馈回路的参数会自动调整,以抑制同步性。虽然这项研究的动机来自神经科学,但其结果与控制各种性质的集合体中的振荡活动相关,因此也与快速发展的网络生理学领域相关。
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引用次数: 0
Editorial: Measurements of cardiorespiratory coupling applied to sports and rehabilitation medicine: insights, implications and perspectives 社论:应用于运动和康复医学的心肺耦合测量:见解、影响和前景
Pub Date : 2024-01-24 DOI: 10.3389/fnetp.2024.1370452
Raphael Martins de Abreu, Victor Ribeiro Neves, Beatrice Cairo
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引用次数: 0
The time-evolving epileptic brain network: concepts, definitions, accomplishments, perspectives 随时间演变的癫痫脑网络:概念、定义、成就和观点
Pub Date : 2024-01-16 DOI: 10.3389/fnetp.2023.1338864
T. Bröhl, T. Rings, Jan Pukropski, R. von Wrede, Klaus Lehnertz
Epilepsy is now considered a network disease that affects the brain across multiple levels of spatial and temporal scales. The paradigm shift from an epileptic focus—a discrete cortical area from which seizures originate—to a widespread epileptic network—spanning lobes and hemispheres—considerably advanced our understanding of epilepsy and continues to influence both research and clinical treatment of this multi-faceted high-impact neurological disorder. The epileptic network, however, is not static but evolves in time which requires novel approaches for an in-depth characterization. In this review, we discuss conceptual basics of network theory and critically examine state-of-the-art recording techniques and analysis tools used to assess and characterize a time-evolving human epileptic brain network. We give an account on current shortcomings and highlight potential developments towards an improved clinical management of epilepsy.
癫痫现在被认为是一种影响大脑多层次空间和时间尺度的网络性疾病。从癫痫病灶--癫痫发作起源的离散皮质区域--到跨越脑叶和半球的广泛癫痫网络,这一范式的转变大大推进了我们对癫痫的理解,并将继续影响这一多方面、影响巨大的神经系统疾病的研究和临床治疗。然而,癫痫网络并不是一成不变的,而是随着时间的推移而不断演变的,这就需要采用新的方法对其进行深入分析。在这篇综述中,我们讨论了网络理论的基本概念,并对用于评估和描述随时间演变的人类癫痫脑网络的最新记录技术和分析工具进行了批判性研究。我们阐述了当前的不足之处,并强调了改善癫痫临床管理的潜在发展方向。
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引用次数: 0
No change in network connectivity measurements between separate rsfMRI acquisition times 在不同的 rsfMRI 采集时间之间,网络连通性测量结果没有变化
Pub Date : 2024-01-15 DOI: 10.3389/fnetp.2024.1342161
Elliot G. Neal, Samantha Schimmel, Zeegan George, Molly Monsour, A. Alayli, Gavin Lockard, Keaton Piper, Stephanie Maciver, Fernando L. Vale, Yarema B. Bezchlibnyk
The role of resting state functional MRI (rsfMRI) is increasing in the field of epilepsy surgery because it is possible to interpolate network connectivity patterns across the brain with a high degree of spatial resolution. Prior studies have shown that by rsfMRI with scalp electroencephalography (EEG), an epileptogenic network can be modeled and visualized with characteristic patterns of connectivity that are relevant to both seizure-related and neuropsychological outcomes after surgery. The aim of this study is to show that a 5-min acquisition time provides reproducible results related to the relevant connectivity metrics when compared to a separately acquired 5-min scan. Fourteen separate rsfMRI sessions from ten different patients were used for comparison, comprised of patients with temporal lobe epilepsy both pre- and post-operation. Results showed that there was no significant difference in any of the connectivity metrics when comparing both 5-min scans to each other. These data support the continued use of a 5-min scan for epileptogenic network modeling in future studies because the inter-scan variability is sufficiently low as not to alter the output metrics characterizing the network connectivity.
静息状态功能磁共振成像(rsfMRI)在癫痫外科领域的作用越来越大,因为它能以较高的空间分辨率插值整个大脑的网络连接模式。先前的研究表明,通过 rsfMRI 和头皮脑电图 (EEG),可以对致痫网络进行建模和可视化,其特征性的连接模式与术后癫痫发作相关结果和神经心理学结果都有关系。本研究旨在证明,与单独采集的 5 分钟扫描相比,5 分钟采集时间可提供与相关连通性指标相关的可重复结果。本研究使用了 10 位不同患者的 14 次独立 rsfMRI 扫描进行比较,这些患者均为颞叶癫痫患者,包括手术前和手术后的患者。结果显示,两组 5 分钟扫描结果的连接性指标没有明显差异。这些数据支持在未来的研究中继续使用 5 分钟扫描进行致痫网络建模,因为扫描间的变异性很低,不会改变表征网络连通性的输出指标。
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引用次数: 0
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Frontiers in Network Physiology
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