transcranial alternating current stimulation

经颅交流电刺激
  • 文章类型: Journal Article
    背景:最近发现Theta-gamma经颅交流电刺激(tACS)可增强年轻人的拇指加速度,健康的参与者,提示在促进运动技能获得方面的潜在作用。鉴于运动技能获取在中风康复中的相关性,theta-gammatACS可能具有治疗卒中幸存者的潜力。
    目的:我们旨在研究theta-gammatACS对青少年运动技能获得的影响,健康参与者和中风幸存者。
    方法:在预先注册的,双盲,随机化,假对照研究,78年轻,健康参与者接受了θ-γ峰耦合(TGP)tACS,theta-gamma波谷耦合(TGT)tACS或假刺激。20名患有慢性中风的个体接受了TGP或假手术。在参与者执行加速度相关的拇指运动任务时,在运动皮层区域应用TACS。使用标准化测试对卒中幸存者进行表征,一个接受额外解剖脑成像的亚组。
    结果:TGP和TGTtACS均未显著改变年轻人的一般运动技能获得,健康队列。相比之下,在中风队列中,与假手术相比,TGP减少了运动技能的获得。探索性分析显示,独立于一般运动技能的获得,接受TGP或TGT的健康参与者的拇指加速度峰值高于接受假手术的参与者.
    结论:尽管theta-gammatACS增加了年轻人的拇指加速度,健康的参与者,与以前的报告一致,在更复杂的运动任务中,它并没有提高整体运动技能的获得。此外,它甚至对中风幸存者的运动技能获得产生不利影响。
    BACKGROUND: Theta-gamma transcranial alternating current stimulation (tACS) was recently found to enhance thumb acceleration in young, healthy participants, suggesting a potential role in facilitating motor skill acquisition. Given the relevance of motor skill acquisition in stroke rehabilitation, theta-gamma tACS may hold potential for treating stroke survivors.
    OBJECTIVE: We aimed to examine the effects of theta-gamma tACS on motor skill acquisition in young, healthy participants and stroke survivors.
    METHODS: In a pre-registered, double-blind, randomized, sham-controlled study, 78 young, healthy participants received either theta-gamma peak-coupled (TGP) tACS, theta-gamma trough-coupled (TGT) tACS or sham stimulation. 20 individuals with a chronic stroke received either TGP or sham. TACS was applied over motor cortical areas while participants performed an acceleration-dependent thumb movement task. Stroke survivors were characterized using standardized testing, with a subgroup receiving additional anatomical brain imaging.
    RESULTS: Neither TGP nor TGT tACS significantly modified general motor skill acquisition in the young, healthy cohort. In contrast, in the stroke cohort, TGP diminished motor skill acquisition compared to sham. Exploratory analyses revealed that, independent of general motor skill acquisition, healthy participants receiving TGP or TGT exhibited greater peak thumb acceleration than those receiving sham.
    CONCLUSIONS: Although theta-gamma tACS increased thumb acceleration in young, healthy participants, consistent with previous reports, it did not enhance overall motor skill acquisition in a more complex motor task. Furthermore, it even had detrimental effects on motor skill acquisition in stroke survivors.
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  • 文章类型: Journal Article
    经颅交流电刺激(tACS)会改变低强度交流电的皮质兴奋性,从而调节异常的大脑振荡。尽管最近研究tACS治疗神经精神疾病的可行性和有效性的研究有所增加,其机制,以及最佳刺激参数,没有完全理解。
    本系统综述旨在汇编人类对tACS神经精神疾病的研究,以描述这些疾病的典型治疗参数并评估其结果。
    通过OVID(MEDLINE,PsycINFO,和Embase),ClinicalTrials.gov,和国际临床试验注册平台。包括在临床试验环境中利用tACS治疗神经精神障碍的研究。
    总共,筛选了783项已发表的研究和373项临床试验;纳入了53项已发表的研究和70项临床试验。已发表的研究表明,偏见的风险较低,由乔安娜·布里格斯研究所批判性评估工具评估。神经认知,精神病患者,抑郁症是tACS治疗最常见的疾病。已发表的研究(58.5%)和注册的临床试验(52%)最常用的伽马频带和tACS通常以2mA峰到峰的强度进行管理,每天一次,每次20次或更少。尽管根据疾病的结果测量和特定病理生理学,目标大脑位置和tACS蒙太奇在研究中有所不同,在已发表的研究(30.2%)和已注册的临床试验(25.6%)中,背外侧前额叶皮质(DLPFC)是最常见的目标.在发表关于tACS结果测量结果的研究中,tACS导致神经认知的症状增强和/或整体精神病理学改善(所有11项研究),精神病(14项研究中有11项),和抑郁症(8项研究中有7项)。此外,17项研究报告了tACS后目标位置的夹带频带周围的脑电图功率谱的变化。
    行为和认知症状受到tACS的积极影响。据报道,与DLPFC相比,γ-tACS后的认知症状发生了最一致的变化。然而,针对每种神经精神疾病的神经影像学研究很少,这凸显了采用生物标志物和机制中心方法进行复制研究的必要性.
    UNASSIGNED: Transcranial alternating current stimulation (tACS) alters cortical excitability with low-intensity alternating current and thereby modulates aberrant brain oscillations. Despite the recent increase in studies investigating the feasibility and efficacy of tACS in treating neuropsychiatric disorders, its mechanisms, as well as optimal stimulation parameters, are not fully understood.
    UNASSIGNED: This systematic review aimed to compile human research on tACS for neuropsychiatric disorders to delineate typical treatment parameters for these conditions and evaluate its outcomes.
    UNASSIGNED: A search for published studies and unpublished registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase), ClinicalTrials.gov, and the International Clinical Trials Registry Platform. Studies utilizing tACS to treat neuropsychiatric disorders in a clinical trial setting were included.
    UNASSIGNED: In total, 783 published studies and 373 clinical trials were screened; 53 published studies and 70 clinical trials were included. Published studies demonstrated a low risk of bias, as assessed by the Joanna Briggs Institute Critical Appraisal Tools. Neurocognitive, psychotic, and depressive disorders were the most common disorders treated with tACS. Both published studies (58.5%) and registered clinical trials (52%) most commonly utilized gamma frequency bands and tACS was typically administered at an intensity of 2 mA peak-to-peak, once daily for 20 or fewer sessions. Although the targeted brain locations and tACS montages varied across studies based on the outcome measures and specific pathophysiology of the disorders, the dorsolateral prefrontal cortex (DLPFC) was the most common target in both published studies (30.2%) and registered clinical trials (25.6%). Across studies that published results on tACS outcome measures, tACS resulted in enhanced symptoms and/or improvements in overall psychopathology for neurocognitive (all 11 studies), psychotic (11 out of 14 studies), and depressive (7 out of 8 studies) disorders. Additionally, 17 studies reported alterations in the power spectrum of the electroencephalogram around the entrained frequency band at the targeted locations following tACS.
    UNASSIGNED: Behavioral and cognitive symptoms have been positively impacted by tACS. The most consistent changes were reported in cognitive symptoms following gamma-tACS over the DLPFC. However, the paucity of neuroimaging studies for each neuropsychiatric condition highlights the necessity for replication studies employing biomarker- and mechanism-centric approaches.
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  • 文章类型: Journal Article
    经颅交流电流刺激(tACS)传递到初级运动皮质(M1)可以增加皮质兴奋性,夹带神经元放电模式,并在简单的运动任务中增加运动技能的获取。这项研究的主要目的是评估在连续三天的练习中应用于M1的tACS对年轻人挑战性的反手投掷任务的运动学习的影响。次要目的是检查tACS对M1兴奋性的影响。这项研究实施了双盲,随机化,SHAM控制,受试者间的实验设计。将总共24名健康的年轻人分为tACS和SHAM组,并进行了三个相同的实验,其中包括对右优势臂进行的徒手投掷试验,同时对左M1应用tACS。上手投掷任务的性能被量化为端点错误。通过经颅磁刺激(TMS)评估右第一背侧骨间(FDI)肌肉的运动诱发电位(MEP),以量化M1兴奋性的变化。当在三天的练习中平均时,与预测试相比,后期测试的终点误差显着降低(p=0.046),但这种下降在tACS组和SHAM组之间没有统计学意义(p=0.474).MEP振幅从前测到后测增加(p=0.003),但这些增加在组间也没有差异(p=0.409).总的来说,主要研究结果表明,与单纯练习(SHAM)相比,对M1多日的tACS在复杂任务中的运动学习效果并不显著.
    Transcranial alternating current stimulation (tACS) delivered to the primary motor cortex (M1) can increase cortical excitability, entrain neuronal firing patterns, and increase motor skill acquisition in simple motor tasks. The primary aim of this study was to assess the impact of tACS applied to M1 over three consecutive days of practice on the motor learning of a challenging overhand throwing task in young adults. The secondary aim was to examine the influence of tACS on M1 excitability. This study implemented a double-blind, randomized, SHAM-controlled, between-subjects experimental design. A total of 24 healthy young adults were divided into tACS and SHAM groups and performed three identical experimental sessions that comprised blocks of overhand throwing trials of the right dominant arm concurrent with application of tACS to the left M1. Performance in the overhand throwing task was quantified as the endpoint error. Motor evoked potentials (MEPs) were assessed in the right first dorsal interosseus (FDI) muscle with transcranial magnetic stimulation (TMS) to quantify changes in M1 excitability. Endpoint error was significantly decreased in the post-tests compared with the pre-tests when averaged over the three days of practice (p = 0.046), but this decrease was not statistically significant between the tACS and SHAM groups (p = 0.474). MEP amplitudes increased from the pre-tests to the post-tests (p = 0.003), but these increases were also not different between groups (p = 0.409). Overall, the main findings indicated that tACS applied to M1 over multiple days does not enhance motor learning in a complex task to a greater degree than practice alone (SHAM).
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  • 文章类型: Journal Article
    (1)背景:耳鸣涉及对没有可识别的相应外部声源的音调或复合噪声的有意识意识。对很多人来说,耳鸣是一种与情绪困扰症状相关的疾病,认知功能障碍,自主唤醒,行为改变,功能性残疾。使用教育或认知行为疗法可以有效地解决许多症状。然而,没有有效降低或改变耳鸣相关神经生理活动的治疗方法,从而降低或改变耳鸣感觉。在这次系统审查中,我们评估了明确针对病理性同步神经活动的耳鸣神经调节疗法的有效性.(2)方法:搜索多个数据库,寻找成人耳鸣神经调节干预的随机对照试验,包括24项试验。评估了偏见的风险,在适当的情况下,进行荟萃分析。(3)结果:很少有试验使用声学,迷走神经,或者经颅交流电刺激,或者双峰刺激技术,神经调节或临床有效性的证据有限。确定了经颅直流电刺激(tDCS)的多项试验,和一个综合证明了耳鸣症状严重程度的显著改善,有利于tDCS与对照,虽然异质性很高。(4)讨论:耳鸣的神经调节是一个新兴但有前途的领域。电刺激技术特别有趣,鉴于电流建模的最新进展,可应用于未来的研究。
    (1) Background: Tinnitus involves the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source. For many people, tinnitus is a disorder associated with symptoms of emotional distress, cognitive dysfunction, autonomic arousal, behavioural changes, and functional disability. Many symptoms can be addressed effectively using education or cognitive behavioural therapy. However, there is no treatment that effectively reduces or alters tinnitus-related neurophysiological activity and thus the tinnitus percept. In this systematic review, we evaluated the effectiveness of neuromodulation therapies for tinnitus that explicitly target pathological synchronous neural activity. (2) Methods: Multiple databases were searched for randomised controlled trials of neuromodulation interventions for tinnitus in adults, with 24 trials included. The risk of bias was assessed, and where appropriate, meta-analyses were performed. (3) Results: Few trials used acoustic, vagal nerve, or transcranial alternating current stimulation, or bimodal stimulation techniques, with limited evidence of neuromodulation or clinical effectiveness. Multiple trials of transcranial direct current stimulation (tDCS) were identified, and a synthesis demonstrated a significant improvement in tinnitus symptom severity in favour of tDCS versus control, although heterogeneity was high. (4) Discussion: Neuromodulation for tinnitus is an emerging but promising field. Electrical stimulation techniques are particularly interesting, given recent advances in current flow modelling that can be applied to future studies.
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  • 文章类型: Published Erratum
    [这更正了文章DOI:10.3389/fnins.2023.1255124。].
    [This corrects the article DOI: 10.3389/fnins.2023.1255124.].
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  • 文章类型: Journal Article
    经颅交流电刺激(tACS)可以向头皮施加不同强度的电流,调节皮质兴奋性和大脑活动。tACS是一种相对较新的神经调节干预措施,现已广泛用于临床实践。与tACS相关的许多论文已在各种期刊上发表。然而,目前还没有客观、直接地介绍tACS的发展趋势和研究热点的文章。因此,这项研究的目的是使用CiteSpace直观地分析最近与tACS相关的出版物,系统详细地总结了当前该领域的研究热点和趋势,并为未来tACS相关研究提供有价值的信息。
    使用了WebofScience核心馆藏科学引文索引扩展的数据库,并从构建到2023年8月4日进行了搜索。使用CiteSpace分析作者,机构,国家,关键词,共同引用的作者,期刊,和参考。
    总共获得677张纸。从2008年到2023年,出版物数量呈增长趋势,尽管有一些波动。在这一领域最有生产力的国家是德国。出版物数量最多的机构是奥尔登堡的卡尔·冯·奥西茨基大学(n=50)。根据布拉德福德的法律,7种期刊被认为是该领域的核心期刊。赫尔曼,CS是出版物最多的作者(n=40),而Antal,A是共同引用次数最多(n=391)和介数中心性(n=0.16)的作者。疾病,脑神经机制和电刺激是该领域的主要研究领域。tACS在不同疾病中的作用,多部位刺激,综合治疗和评价是未来研究的热点和趋势。
    tACS具有研究价值和研究潜力,越来越多的研究者开始关注它。本文献计量学研究的发现提供了tACS临床研究的现状和趋势,可能有助于研究人员识别热点并探索该领域的新研究方向。
    UNASSIGNED: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research.
    UNASSIGNED: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references.
    UNASSIGNED: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford\'s law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends.
    UNASSIGNED: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.
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  • 文章类型: Journal Article
    背景:眨眼反射的兴奋性,通过配对的电刺激反应评估,已使用传统的非侵入性神经刺激技术进行调制。最近,经颅交流电流刺激(tACS)作为一种工具出现,以调节涉及各种运动的大脑振荡,感性的,和认知功能。这项研究旨在研究20Hz和10HztACS会话对初级运动皮层的影响及其对眨眼反射兴奋性的影响。
    方法:15名健康志愿者进行了10分钟的tACS会话(强度1mA),将有源/参比电极放置在C4/Pz上,提供20Hz,10-Hz,和假刺激。眨眼反射恢复周期(BRrc)使用R2振幅比在(T0)之前的各种刺激间隔(ISIs)进行评估,在(T1)之后,和30分钟后tACS(T2)。
    结果:与基线(T0)相比,10-Hz和20-HztACS会话在T1(10-Hz:p=0.02;20-Hz:p<0.001)和T2(10-Hz:p=0.01;20-Hz:p<0.001)处均显著增加R2比率。值得注意的是,在T1(p=0.04)和T2(p<0.001)下,与假手术相比,20Hz的tACS诱导眨眼反射兴奋性的显着增加。
    结论:这项研究证明了tACS对三叉神经-面部反射回路的调节作用,对BRrc产生持久影响。β波段频率tACS表现出比α波段频率更明显的影响,强调运动皮层中β波段振荡对眨眼反射兴奋性调制的影响作用。
    BACKGROUND: The blink reflex excitability, assessed through paired electrical stimuli responses, has been modulated using traditional non-invasive neurostimulation techniques. Recently, transcranial Alternating Current Stimulation (tACS) emerged as a tool to modulate brain oscillations implicated in various motor, perceptual, and cognitive functions. This study aims to investigate the influence of 20-Hz and 10-Hz tACS sessions on the primary motor cortex and their impact on blink reflex excitability.
    METHODS: Fifteen healthy volunteers underwent 10-min tACS sessions (intensity 1 mA) with active/reference electrodes placed over C4/Pz, delivering 20-Hz, 10-Hz, and sham stimulation. The blink reflex recovery cycle (BRrc) was assessed using the R2 amplitude ratio at various interstimulus intervals (ISIs) before (T0), immediately after (T1), and 30 min post-tACS (T2).
    RESULTS: Both 10-Hz and 20-Hz tACS sessions significantly increased R2 ratio at T1 (10-Hz: p = 0.02; 20-Hz: p < 0.001) and T2 (10-Hz: p = 0.01; 20-Hz: p < 0.001) compared to baseline (T0). Notably, 20-Hz tACS induced a significantly greater increase in blink reflex excitability compared to sham at both T1 (p = 0.04) and T2 (p < 0.001).
    CONCLUSIONS: This study demonstrates the modulatory effect of tACS on trigemino-facial reflex circuits, with a lasting impact on BRrc. Beta-band frequency tACS exhibited a more pronounced effect than alpha-band frequency, highlighting the influential role of beta-band oscillations in the motor cortex on blink reflex excitability modulation.
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  • 文章类型: Journal Article
    Theta振荡支持记忆形成,但是它们对前额叶皮层(PFC)和海马体之间的交流的确切贡献尚不清楚。我们使用经颅交流电流刺激(tACS)测试了theta振荡作为两个区域之间的通信链接以形成记忆的功能相关性。健康,年轻的参与者学习了两个荷兰语-德语单词对列表,并立即检索,延迟30分钟.在编码组中(N=30),在列表1的编码期间应用tACS。清单2用于测试刺激后效应。在检索组(N=23)中,我们在延迟召回期间受到了刺激。在这两组中,我们在前额叶和节奏顶叶部位双侧应用了tACS,使用个性化的θ频率或15Hz(作为对照),根据主题内设计。theta-tACS刺激不会改变整体学习表现。探索性分析显示,在theta-tACS之后学习单词对时,即时回忆有所改善(列表2)。在检索过程中应用theta-tACS对记忆有不利影响。没有观察到各个频带的功率变化。我们的结果不支持双边tACS在任务过程中影响PFC和海马之间的交流可以改善记忆力的观点。然而,我们确实发现有证据表明,在即时和延迟回忆期间,直接刺激有负面干扰效应的趋势.对记忆有益影响的提示仅发生在刺激的副作用中。未来的研究需要进一步检查刺激期间和之后对记忆形成的影响。
    Theta oscillations support memory formation, but their exact contribution to the communication between prefrontal cortex (PFC) and the hippocampus is unknown. We tested the functional relevance of theta oscillations as a communication link between both areas for memory formation using transcranial alternating current stimulation (tACS). Healthy, young participants learned two lists of Dutch-German word pairs and retrieved them immediately and with a 30-min delay. In the encoding group (N = 30), tACS was applied during the encoding of list 1. List 2 was used to test stimulation aftereffects. In the retrieval group (N = 23), we stimulated during the delayed recall. In both groups, we applied tACS bilaterally at prefrontal and tempo-parietal sites, using either individualized theta frequency or 15 Hz (as control), according to a within-subject design. Stimulation with theta-tACS did not alter overall learning performance. An exploratory analysis revealed that immediate recall improved when word-pairs were learned after theta-tACS (list 2). Applying theta-tACS during retrieval had detrimental effects on memory. No changes in the power of the respective frequency bands were observed. Our results do not support the notion that impacting the communication between PFC and the hippocampus during a task by bilateral tACS improves memory. However, we do find evidence that direct stimulation had a trend for negatively interfering effects during immediate and delayed recall. Hints for beneficial effects on memory only occurred with aftereffects of the stimulation. Future studies need to further examine the effects during and after stimulation on memory formation.
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  • 文章类型: Journal Article
    脑电刺激,特别是非侵入性脑刺激(NIBS)技术,如经颅电刺激(tES),已经成为各种精神疾病的有希望的治疗方法,包括抑郁症,焦虑,和创伤后应激障碍。tES技术,例如经颅直流电刺激(TDCS),经颅交流电流刺激(TACS),和经颅随机噪声刺激(tRNS),是经济有效且安全的干预措施,旨在使用各种方式影响大脑中的神经元回路。尽管tES在治疗精神疾病方面显示出有效性,缺乏考虑其临床意义的综合论文。因此,本综述旨在评估tES的临床意义,并为精神疾病的治疗提供实用指导。此外,这篇综述概述了tES技术及其作用机制,并总结了最近的临床研究,这些研究已检查了tES用于精神疾病。
    Brain electrical stimulation, particularly non-invasive brain stimulation (NIBS) techniques such as transcranial electrical stimulation (tES), have emerged as a promising treatment for various psychiatric disorders, including depression, anxiety, and post-traumatic stress disorder. tES techniques, such as transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), are cost-effective and safe interventions that are designed to affect neuronal circuits in the brain using various modalities. Although tES has shown effectiveness in the treatment of psychiatric disorders, there is a lack of comprehensive papers that consider its clinical implications. Therefore, this review aims to evaluate the clinical implications of tES and provide practical guidance for the treatment of psychiatric illnesses. Moreover, this review provides an overview of tES techniques and their mechanisms of action and summarizes recent clinical studies that have examined the use of tES for psychiatric disorders.
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  • 文章类型: Journal Article
    治疗性电刺激,例如经颅皮层刺激和周围体感刺激,用于改善中风患者的运动功能。我们假设这些刺激通过调节新的共同信号通路在缺血性卒中亚急性期发挥神经保护作用。用高清晰度(HD)-经颅交流电流刺激(tACS;20Hz,89.1A/mm2),HD-经颅直流电刺激(tDCS;强度,55A/mm2;电荷密度,66,000C/m2),或电针(EA,2Hz,1mA)在中风的早期阶段。使用行为运动功能测试评估治疗效果。使用转录组学和其他生物医学分析确定了潜在的机制。所有治疗性电动工具都减轻了缺血性中风引起的运动功能障碍。我们使用转录组分析专注于电刺激参与细胞凋亡和细胞死亡的常见基因,并选择了11个最有效的靶标(Trem2,S100a9,Lgals3,Tlr4,Myd88,NF-kB,STAT1,IL-6,IL-1β,TNF-α,和Iba1)。随后的研究表明,电刺激调节炎症细胞因子,包括IL-1β和TNF-α,通过调节STAT1和NF-kB激活,特别是在变形虫小胶质细胞中;此外,电刺激通过激活神经营养因子增强神经元存活,包括BDNF和FGF9。应用于经颅皮质或外周神经水平以促进功能恢复的治疗性电刺激可以通过调节常见的神经元死亡途径和上调神经营养因子来改善神经保护。因此,联合经颅皮质和外周体感刺激可能发挥协同神经保护作用,进一步增强对缺血性卒中患者运动功能障碍的有益作用。
    Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm2), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm2; charge density, 66,000 C/m2), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1β, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1β and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.
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