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Clinical Effect on Cortical Reactivity of Theta Burst Versus High-Frequency Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease: A TMS-EEG Study 高频重复经颅磁刺激对帕金森病皮层反应性的临床影响:一项TMS-EEG研究
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-11 DOI: 10.1111/cns.70605
Jiajing Wu, Sheng Zhuang, Yinlian Han, Fan Gao, Chengjie Mao, Jing Chen, Chun-feng Liu

Background

Both high-frequency repeated transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) are believed to enhance cortical excitability. However, clinical comparison of their benefits for motor improvement in Parkinson's disease (PD) as well as their underlying neurophysiological changes remain unelucidated.

Objective

To compare the clinical effect of rTMS versus iTBS on motor improvement and explore their influence on cortical reactivity using resting state electroencephalogram (EEG) and TMS-EEG.

Methods

Idiopathic PD patients were randomized in a single-blind, controlled trial, and received 10 sessions of either 10-Hz rTMS or iTBS applied to the bilateral primary motor cortex (M1). Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale. Cortical reactivity was assessed by resting state EEG and TMS-evoked potentials.

Results

Included were 52 PD patients (mean [SD] age 66.2 [5.8] years). Compared to 10 Hz rTMS, iTBS was more efficient in alleviating tremor symptoms. In the iTBS group, the global mean field amplitude of P60 was significantly higher after stimulation over contralateral M1 of the affected side and was inversely correlated with motor improvement. In the 10 Hz rTMS group, the global mean field amplitude of P30 evoked by ipsilateral M1 increased significantly. The combination of oscillation and connectivity of δ frequency in the frontal cortex of PD provided a decent model in predicting iTBS responders at baseline.

Conclusion

Compared with high-frequency rTMS, iTBS applied to M1 was more effective in improving tremor symptoms in PD. The two non-invasive stimulation modalities appear to exert their effects through distinct neurophysiological pathways, as measured by EEG and TMS-EEG.

高频重复经颅磁刺激(rTMS)和间歇θ波爆发刺激(iTBS)都被认为能增强皮层的兴奋性。然而,它们对帕金森病(PD)运动改善的益处及其潜在的神经生理变化的临床比较仍不清楚。目的通过静息状态脑电图(EEG)和TMS-EEG分析,比较rTMS与iTBS对运动改善的临床效果,探讨其对脑皮层反应性的影响。方法将特发性PD患者随机纳入单盲对照试验,接受10次10 hz rTMS或iTBS(双侧初级运动皮质)治疗。使用统一帕金森病评定量表评估运动症状。通过静息状态脑电图和tms诱发电位评估皮层反应性。结果纳入52例PD患者(平均[SD]年龄66.2[5.8]岁)。与10hz rTMS相比,iTBS在缓解震颤症状方面更有效。在iTBS组中,刺激对侧M1后,P60的整体平均场振幅显著升高,并与运动改善呈负相关。在10 Hz rTMS组,同侧M1诱发的P30的全球平均场振幅显著增加。PD额叶皮层δ频率振荡和连通性的结合为预测iTBS基线反应提供了一个良好的模型。结论与高频rTMS相比,iTBS对PD震颤症状的改善更有效。通过EEG和TMS-EEG测量,两种非侵入性刺激方式似乎通过不同的神经生理途径发挥作用。
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引用次数: 0
Fracture Risk Associated With Dimethyl Fumarate Treatment in Multiple Sclerosis Patients: Population Heterogeneity and Temporal Patterns 多发性硬化症患者富马酸二甲酯治疗与骨折风险相关:人群异质性和时间模式
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-11 DOI: 10.1111/cns.70612
Dongdong He, Jingkai Di, Peirui Jiang, Lujia Liu, Feida Wang, Chuan Xiang

Objective

Dimethyl fumarate (DMF) is currently recommended as a first-line therapy for multiple sclerosis (MS). Investigating its adverse events (AEs) holds significant clinical importance. This study aimed to explore the association between DMF and fracture-related AEs.

Methods

Data from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q3 2024) were analyzed using disproportionality analysis. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayes Geometric Mean (EBGM) were employed to identify and characterize AEs. Age- and gender-specific subgroup analyses were conducted to evaluate AE patterns. Additionally, Weibull distribution analysis was performed to assess the temporal relationship of AE onset.

Results

Overall, spinal fusion fracture (ROR = 13.13, 95% CI: 1.73–99.86) and coccyx fracture (ROR = 3.05, 95% CI: 1.92–4.86) exhibited the strongest signals. Gender and age heterogeneity were observed in DMF-associated fracture risks. Female patients showed the highest signals for spinal fusion bone fracture (ROR = 13.13) and coccyx fracture (ROR = 2.80), while males predominantly exhibited patella (ROR = 4.94) and scapula fractures (ROR = 3.68). Age stratification revealed elevated risks of forearm fracture (ROR = 10.29, 95% CI: 4.24–24.96) and ankle fracture (ROR = 5.63, 95% CI: 4.32–7.35) in elderly patients, whereas younger populations displayed diverse multi-site fractures. Time-to-onset (TTO) analysis indicated that 63.62% of fractures occurred within the first 2 years of the treatment cycle, with a median onset time of 506 days. Weibull distribution modeling indicated that DMF's failure pattern aligned with an early failure-type curve.

Conclusion

DMF use is associated with an increased risk of fracture-related AEs, with demographic variations in susceptibility. This study provides critical insights into the safety profile of DMF in MS management, underscoring the need for vigilance in high-risk populations.

富马酸二甲酯(DMF)目前被推荐作为多发性硬化症(MS)的一线治疗药物。研究其不良事件(ae)具有重要的临床意义。本研究旨在探讨DMF与骨折相关ae之间的关系。方法对FDA不良事件报告系统(FAERS)数据库2004年第一季度至2024年第三季度的数据进行歧化分析。采用报告优势比(ROR)、比例报告比(PRR)、信息成分(IC)和经验贝叶斯几何平均(EBGM)对ae进行识别和表征。采用年龄和性别特异性亚组分析来评估AE模式。此外,采用威布尔分布分析评估AE发作的时间关系。结果脊柱融合骨折(ROR = 13.13, 95% CI: 1.73-99.86)和尾骨骨折(ROR = 3.05, 95% CI: 1.92-4.86)表现出最强的信号。dmf相关骨折风险存在性别和年龄异质性。女性患者脊柱融合骨折(ROR = 13.13)和尾骨骨折(ROR = 2.80)的信号最高,而男性患者以髌骨骨折(ROR = 4.94)和肩胛骨骨折(ROR = 3.68)为主。年龄分层显示,老年患者前臂骨折(ROR = 10.29, 95% CI: 4.24-24.96)和踝关节骨折(ROR = 5.63, 95% CI: 4.32-7.35)的风险较高,而年轻人则表现出不同的多部位骨折。发病时间(TTO)分析显示,63.62%的骨折发生在治疗周期的前2年内,中位发病时间为506天。Weibull分布模型表明,DMF的失效模式与早期失效型曲线一致。结论:DMF的使用与骨折相关ae的风险增加有关,且易感性存在人口统计学差异。这项研究为DMF在多发性硬化症治疗中的安全性提供了重要的见解,强调了对高危人群保持警惕的必要性。
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引用次数: 0
Deer Antler S-Adenosylmethionine Ameliorates Depression-Like Behaviors and Neuroinflammation in CUMS Mice 鹿茸s -腺苷蛋氨酸改善CUMS小鼠抑郁样行为和神经炎症
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-10 DOI: 10.1111/cns.70569
Yongjian Liu, Chenyang Han, Li Guo, Wenyan Li, Shasha wu, Jian Sheng, Liping Zhai, Heping Shen, Genghuan Wang

Aim

To investigate the effects and mechanisms of S-adenosylmethionine (SAM) from deer antler on improving depression-like behaviors in chronic unpredictable mild stress (CUMS) mice.

Methods

The CUMS method was used to establish a mouse depression model. The relationship between SAM and HIF-1α was analyzed by small molecule-protein docking and molecular dynamics simulation.

Results

Network pharmacology analysis showed that the effect of SAM is related to HIF-1α. When shRNA-HIF-1α was used to silence the expression of HIF-1α, the effect of SAM was inhibited. The improvement of depression-like behaviors in mice was not significant, and inflammatory factors were no longer further downregulated.

Conclusion

SAM can improve depression-like behaviors in CUMS mice and enhance their mobility. SAM inhibits neuroinflammation and glycolysis, and also suppresses the activation of microglia.

目的探讨鹿角s -腺苷蛋氨酸(SAM)对慢性不可预测轻度应激(CUMS)小鼠抑郁样行为的改善作用及其机制。方法采用CUMS法建立小鼠抑郁模型。通过小分子-蛋白对接和分子动力学模拟分析了SAM与HIF-1α之间的关系。结果网络药理学分析显示,SAM的作用与HIF-1α有关。用shRNA-HIF-1α沉默HIF-1α表达后,SAM的作用被抑制。小鼠抑郁样行为改善不显著,炎症因子不再进一步下调。结论SAM能改善CUMS小鼠抑郁样行为,增强其活动能力。SAM抑制神经炎症和糖酵解,也抑制小胶质细胞的激活。
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引用次数: 0
Repopulating Microglia Suppress Peripheral Immune Cell Infiltration to Promote Poststroke Recovery 再生小胶质细胞抑制外周免疫细胞浸润促进脑卒中后恢复。
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-10 DOI: 10.1111/cns.70565
Ligen Shi, Lingxiao Lu, Jun Hu, Jiarui Chen, Qia Zhang, Ziyang Jin, Zhen Wang, Zhe Zheng, Jianmin Zhang

Aims

Sustained neuroinflammation following ischemic stroke impedes post-injury tissue repairment and neurological functional recovery. Developing innovative therapeutic strategies that simultaneously suppress detrimental inflammatory cascades and facilitate neurorestorative processes is critical for improving long-term rehabilitation outcomes.

Methods

We employed a microglia depletion-repopulation paradigm by administering PLX5622 for 7 days post-ischemia; followed by a 7-day withdrawal period to allow microglia repopulation. Single-cell transcriptomics, behavioral testing, cytokine arrays, flow cytometry, and immunofluorescence were used to assess the effects of microglia repopulation and delineate the transition of reshaped immune microenvironment.

Results

PLX5622 administration reshaped the poststroke immune microenvironment, promoting neurofunctional recovery. Repopulated microglia adopted a homeostatic phenotype, increasing homeostatic states by ~14.36% and reducing pro-inflammatory states by ~20.17%. This reshaped environment suppressed T cell exhaustion, limited neutrophil terminal differentiation, and promoted a phagocytic macrophage phenotype. Furthermore, we identified that these transitions in infiltrating immune cells may be driven by reduced chemokine production, enhanced blood–brain barrier (BBB) integrity, and transcriptional reprogramming.

Conclusion

Transient microglial depletion and repopulation via PLX5622 during the acute phase post stroke facilitate the recovery of neurological function. This immunomodulatory strategy offers a promising and clinically translationally relevant approach to enhance functional recovery following ischemic brain injury.

目的:缺血性脑卒中后持续的神经炎症阻碍损伤后组织修复和神经功能恢复。开发创新的治疗策略,同时抑制有害的炎症级联反应和促进神经恢复过程是改善长期康复结果的关键。方法:我们采用小胶质细胞消耗-再生模式,缺血后给予PLX5622 7天;然后是7天的停药期,让小胶质细胞再生。单细胞转录组学、行为测试、细胞因子阵列、流式细胞术和免疫荧光技术被用于评估小胶质细胞再生的影响,并描绘重塑免疫微环境的转变。结果:PLX5622可重塑脑卒中后免疫微环境,促进脑卒中后神经功能恢复。再生的小胶质细胞采用稳态表型,稳态状态增加了约14.36%,促炎状态减少了约20.17%。这种重塑的环境抑制T细胞衰竭,限制中性粒细胞末端分化,并促进吞噬巨噬细胞表型。此外,我们发现浸润性免疫细胞中的这些转变可能是由趋化因子产生减少、血脑屏障(BBB)完整性增强和转录重编程驱动的。结论:脑卒中后急性期短暂性小胶质细胞耗竭和通过PLX5622再生有助于神经功能的恢复。这种免疫调节策略为增强缺血性脑损伤后的功能恢复提供了一种有前途的和临床翻译相关的方法。
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引用次数: 0
Individualized Frequency-Dependent Stimulation to the Anterior Nucleus of the Thalamus May Improve Antiepileptic Effects in Patients With Focal Epilepsy 个体化频率依赖性刺激丘脑前核可能改善局灶性癫痫患者的抗癫痫效果。
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-10 DOI: 10.1111/cns.70611
Ying Gao, Hao Yan, Xueyuan Wang, Guiliang Hao, Liang Qiao, Wei Shu, Duanyu Ni, Guoguang Zhao, Liankun Ren, Tao Yu

Aim

A total of 30% of individuals with epilepsy are resistant to drug treatment. Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) shows promise for treating drug-resistant epilepsy (DRE), but further research is needed to optimize DBS parameters, including stimulation frequency. This study aimed to reveal the optimal frequency for ANT-DBS by testing the real-time effects of various stimulation frequencies on the ANT among patients undergoing stereoelectroencephalography (SEEG) electrode implantation.

Methods

Eleven patients (8 males; mean age, 24.2 years; mean epilepsy duration, 13.5 years) were enrolled. Postoperative electrode reconstruction identified ANT contacts for bipolar stimulation between 10 Hz and 100 Hz at 10-Hz increments, with a 1-min interval between stimuli. The effects were analyzed on the basis of spike count, power spectral density, and causal flow.

Results

Our study revealed that ANT stimulation suppresses seizure focus activity and modulates brain network dynamics, with the effects varying by individual characteristics and frequency. Stimulation at 10–70 Hz reduced spikes (> 50%) and PSD (p < 0.05) in the epileptogenic region while also influencing network connectivity between the epileptogenic zone and adjacent cortical regions, including the frontal, temporal, and insular lobes, as well as the overall brain network.

Conclusions

Instead of using a fixed high frequency for ANT-DBS, the optimal frequency should be selected for each patient. Patients who do not respond well to high-frequency ANT-DBS can use a lower frequency, such as 10–70 Hz.

目的:总共有30%的癫痫患者对药物治疗有抗药性。丘脑前核深部脑刺激(DBS)有望治疗耐药癫痫(DRE),但需要进一步研究优化DBS参数,包括刺激频率。本研究旨在通过测试不同刺激频率对立体脑电图(SEEG)电极植入患者ANT的实时影响,揭示ANT- dbs的最佳频率。方法:纳入11例患者,其中男性8例,平均年龄24.2岁,平均癫痫持续时间13.5年。术后电极重建确定了以10 Hz和100 Hz为增量的双极刺激的ANT接触,刺激间隔为1分钟。根据脉冲数、功率谱密度和因果流分析了这些效应。结果:我们的研究表明,ANT刺激抑制癫痫发作焦点活动并调节脑网络动态,其效果因个体特征和频率而异。10-70 Hz的刺激可降低峰值(> 50%)和PSD (p)。结论:ANT-DBS不应使用固定的高频,而应为每位患者选择最佳频率。对高频ANT-DBS反应不佳的患者可以使用较低的频率,如10-70 Hz。
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引用次数: 0
Visuomotor Training to Enhance Proprioception of Contralateral Wrist Based on the Cross-Transfer Effect 基于交叉传递效应的视觉运动训练增强对侧腕本体感觉。
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-10 DOI: 10.1111/cns.70504
Yizhao Wang, Liping Huang, Zhuang Wang, Ting Liu

Background

Neurological diseases such as stroke or Parkinson's disease are often accompanied by weakening or loss of proprioception, which seriously affects the motor control ability of the patients. However, proprioception rehabilitation is challenging due to the pain caused by impaired joints and the hard efforts that patients have to make during training. This study investigated the cross-transfer effect of short-term visuomotor training to the untrained wrist from the trained wrist, from both views of behavioral results and brain activity analyses.

Methods

Thirty healthy volunteers aged 25.53 ± 4.95 years were recruited for this study. They were randomly assigned into two groups: the visuomotor (n = 15) group performed visuomotor training (VM group) and the conventional training (n = 15) group (CT group) performed flexion and extension training on the right wrist. Behavioral tests (movement accuracy error, MAE) were performed both before and after training, with electroencephalogram (EEG) recorded. The movement-related cortical potentials (MRCPs), event-related potentials (ERPs) and event-related spectral perturbation (ERSP) were calculated in the test session before and after training.

Results

Behavioral results showed that after visuomotor training of the right wrist on the VM group, the mean MAE of both the right wrist and untrained left wrist were reduced (p < 0.05) after training. EEG topography showed reduced brain activity as the behavioral test task became familiar. ERPs showed a decrease in amplitude during the behavioral test for both trained and untrained wrist movements. MRCPs latency significantly increased at C3 and C4 while amplitude decreased at C3 and Cz for the right wrist; latency significantly increased at C3 while amplitude decreased at Cz for the left wrist. Increased power at CP3 for the right wrist and CP4 for the left wrist in α-frequency ERSP after VM was observed; reduced power in β-frequency ERSP after VM was observed for both wrists. For the CT group, the mean MAE of the trained right wrist increased (p < 0.05) after training, while the untrained left wrist showed no statistical significance. No significant energy changes corresponding to the left/right wrist were observed in EEG topography after training. There was a noticeable decrease in ERPs amplitude at the central and parietal regions for both the left and right wrists. The MRCPs latency significantly increased at C3 for the right wrist; however, the latency and amplitude did not significantly change for the left wrist. Dec

背景:脑卒中、帕金森病等神经系统疾病常伴有本体感觉减弱或丧失,严重影响患者的运动控制能力。然而,由于关节受损引起的疼痛和患者在训练过程中必须付出的艰苦努力,本体感觉康复具有挑战性。本研究从行为结果和脑活动分析两方面探讨了短期视觉运动训练从训练腕向未训练腕的交叉传递效应。方法:招募年龄25.53±4.95岁的健康志愿者30名。随机分为两组:视觉运动组(n = 15)进行视觉运动训练(VM组),常规训练组(n = 15)进行右腕屈伸训练(CT组)。训练前后分别进行行为测试(运动精度误差,MAE),并记录脑电图。在训练前后计算运动相关皮质电位(MRCPs)、事件相关电位(ERPs)和事件相关谱摄动(ERSP)。结果:行为学结果显示,VM组进行右腕视觉运动训练后,右腕和未训练的左腕平均MAE均降低(p)。结论:右腕视觉运动训练使训练和未训练的腕关节本体感觉均得到改善,表现出交叉传递效应。这些发现表明,视觉运动训练可以用于康复方案,以改善神经系统疾病患者的本体感觉,提供一种更少痛苦和更有效的方法来恢复运动控制。
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引用次数: 0
Exploring Heterogeneity in Vestibular Migraine Using Individualized Differential Structural Covariance Network Analysis 应用个体化微分结构协方差网络分析探讨前庭偏头痛的异质性
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-08 DOI: 10.1111/cns.70599
Wen Chen, Hongru Zhao, Lingling Dai, Xing Xiong, Qifang Feng, Jun Ke, Chunhong Hu

Background

The high heterogeneity in vestibular migraine (VM) complicates understanding its precise pathophysiological mechanisms and identifying potential biomarkers. This study investigated the heterogeneity in VM using a newly proposed method called Individualized Differential Structural Covariance Network (IDSCN) analysis.

Methods

Structural T1-weighted MRI scans were performed on 55 patients with VM and 65 healthy controls, and an IDSCN was constructed for each patient. We studied the extent of heterogeneity in the IDSCNs, summarized the distribution of differential edges, and clustered the patients into subtypes with the shared differential edges. Imaging–clinical association analyses were conducted on both the subtype classification and the differential edges exhibiting significant inter-subtype differences.

Results

Patients with VM demonstrated notable heterogeneity in the number of significantly altered IDSCN edges, while sharing several common differential connections that were mainly distributed among the parietal, subcortical, and cerebellar regions. Two robust and distinct neuroanatomical subtypes of VM were identified, which were associated with headache frequency. The differential edge between the left paracentral lobule and right pallidum was associated with both headache frequency and occurrence.

Conclusions

These findings indicate the importance of considering individual differences in VM research and may offer insights for precise diagnosis and individualized treatment of the disease.

背景前庭偏头痛(VM)的高度异质性使得理解其精确的病理生理机制和识别潜在的生物标志物变得复杂。本研究采用一种新提出的个体化差分结构协方差网络(IDSCN)分析方法来研究虚拟机的异质性。方法对55例VM患者和65例健康对照者进行t1加权MRI扫描,并对每例患者构建IDSCN。我们研究了idscn的异质性程度,总结了差异边的分布,并将患者聚类为具有共享差异边的亚型。对亚型分类和差异边缘进行影像学-临床关联分析,显示亚型间存在显著差异。结果VM患者在IDSCN边缘显著改变的数量上表现出显著的异质性,而在顶叶区、皮层下区和小脑区有几个共同的差异连接。确定了两种健壮且独特的VM神经解剖学亚型,它们与头痛频率相关。左中央旁小叶和右苍白球之间的不同边缘与头痛的频率和发生有关。结论这些发现表明在VM研究中考虑个体差异的重要性,并可能为疾病的精确诊断和个性化治疗提供见解。
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引用次数: 0
Neuroprotective Effects of Transcranial Pulsed Current Stimulation: Modulation of Microglial Polarization in Traumatic Brain Injury 经颅脉冲电流刺激的神经保护作用:外伤性脑损伤中小胶质细胞极化的调节
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-07 DOI: 10.1111/cns.70606
Peng Yao, Bingkai Ren, Qianhui Zhou, Yang Bai, Zhen Feng

Objective

Traumatic brain injury (TBI), a prevalent neurological disorder worldwide, is marked by varying degrees of neurological dysfunction. A key contributor to secondary damage and impediments in the repair process is the unregulated activation of microglia, which triggers neuroinflammation. Emerging evidence highlights the therapeutic potential of transcranial pulsed current stimulation (tPCS) in mitigating neurological deficits. However, despite these promising neuroprotective effects, its role and exact mechanisms in TBI remain unclear.

Methods

Herein, a mouse model of TBI was established, and daily 30-min tPCS treatments were administered for five consecutive days. Subsequently, we conducted comprehensive assessments of neurological function, microglial activation status, and neuroplasticity in the treated subjects. Additionally, a co-culture system of BV2 and HT22 cells was developed, using LPS to activate microglia, to explore potential neuroprotective mechanisms.

Results

Our findings revealed that tPCS plays a crucial role in mitigating neuroinflammation and promoting neurological recovery following TBI. The underlying mechanism likely involves tPCS enhancing orexin-A (OX-A) expression, which subsequently suppresses the NF-κB pathway and promotes the expression of neurorepair-related markers. In vitro experiments further clarified these findings, demonstrating that OX-A effectively inhibited LPS-induced M1 microglial polarization and promoted a shift towards the M2 phenotype. Furthermore, OX-A significantly reduced intracellular ROS production and microglia-induced neuronal apoptosis.

Conclusion

These findings indicate that tPCS regulates microglial phenotype via the OX-A/NF-κB pathway, thereby suppressing neuroinflammation and enhancing neuroplasticity. These results provide a new perspective for the rehabilitation of individuals with TBI.

目的外伤性脑损伤(TBI)是一种世界范围内普遍存在的神经系统疾病,其特征是不同程度的神经功能障碍。在修复过程中造成继发性损伤和障碍的一个关键因素是小胶质细胞的不受调节的激活,这会引发神经炎症。新出现的证据强调了经颅脉冲电流刺激(tPCS)在减轻神经功能缺陷方面的治疗潜力。然而,尽管有这些有希望的神经保护作用,其在创伤性脑损伤中的作用和确切机制尚不清楚。方法建立脑外伤小鼠模型,每天给予30 min tPCS治疗,连续5 d。随后,我们对治疗对象的神经功能、小胶质细胞激活状态和神经可塑性进行了综合评估。此外,我们建立了BV2和HT22细胞的共培养系统,使用LPS激活小胶质细胞,以探索潜在的神经保护机制。结果tPCS在减轻脑外伤后神经炎症和促进神经功能恢复方面具有重要作用。其潜在机制可能涉及tPCS增强orexin-A (OX-A)表达,从而抑制NF-κB通路并促进神经修复相关标志物的表达。体外实验进一步阐明了这些发现,表明OX-A有效抑制lps诱导的M1小胶质细胞极化,促进M2表型的转变。此外,OX-A显著减少细胞内ROS的产生和小胶质细胞诱导的神经元凋亡。结论tPCS通过OX-A/NF-κB通路调节小胶质细胞表型,从而抑制神经炎症,增强神经可塑性。这些结果为创伤性脑损伤患者的康复治疗提供了新的视角。
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引用次数: 0
Altered Sensorimotor Cortical Activities During Forearm Movement in Humans With Spinal Cord Injury 脊髓损伤患者前臂运动过程中感觉运动皮层活动的改变
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-07 DOI: 10.1111/cns.70601
Bo Li, Honghao Liu, Guanghui Li, Yiran Lang, Rongyu Tang, Fengbao Yang

Aims

Decoding the motor intention by electroencephalography to control external devices is an effective method of helping spinal cord injury (SCI) patients to regain motor function. Still, SCI patients have much lower accuracy in the decoding of motor intentions compared to healthy individuals, which severely hampers the clinical application. However, the underlying neural mechanisms are still unknown. The aim of this paper is to investigate changes in cortical activities after SCI, which are direct determinants of motor decoding performance.

Methods

We performed source localization analyses to investigate the changes in motor-related cortical regions after SCI. Moreover, we measured the power spectral density values and event-related spectral perturbation values to assess the characteristics of the changes in cortical potentials.

Results

We found that motor-related independent component clusters decreased while attempting upper limb movement after SCI. Additionally, the activities in the sensorimotor cortex obviously attenuated after SCI. theta, alpha, and beta band power modulation obviously altered in SCI individuals. Furthermore, the latency of the largest power increase or decrease between SCI and healthy individuals demonstrated obvious differences.

Conclusion

Our findings revealed changes in motor-related cortical areas after SCI, which were crucial for improving the accuracy of motor intention decoding and advancing the clinical application.

目的通过脑电图解码运动意图来控制外设是帮助脊髓损伤(SCI)患者恢复运动功能的有效方法。然而,脊髓损伤患者对运动意图的解码准确率远低于健康人,严重阻碍了其临床应用。然而,潜在的神经机制尚不清楚。本文的目的是研究脊髓损伤后大脑皮层活动的变化,这是运动解码表现的直接决定因素。方法采用脑源定位分析方法研究脊髓损伤后运动相关皮质区的变化。此外,我们还测量了功率谱密度值和事件相关谱摄动值,以评估皮质电位变化的特征。结果我们发现在脊髓损伤后尝试上肢运动时,运动相关的独立成分簇减少。脊髓损伤后感觉运动皮层活动明显减弱。θ、α和β波段功率调制在脊髓损伤个体中明显改变。此外,脊髓损伤与健康个体最大功率增加或减少的潜伏期也存在明显差异。结论脊髓损伤后运动相关皮质区的变化,对提高运动意向解码的准确性和促进临床应用具有重要意义。
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引用次数: 0
The Role of P62/Nrf2/Keap1 Signaling Pathway in Lead-Induced Neurological Dysfunction P62/Nrf2/Keap1信号通路在铅诱导的神经功能障碍中的作用
IF 5 1区 医学 Q1 NEUROSCIENCES Pub Date : 2025-09-05 DOI: 10.1111/cns.70566
Dongjie Peng, Peiqi Wei, Zhenning Li, Ruokun Wei, Huishuai Li, Shaojun Li

Background

Lead (Pb) exposure is recognized for its contribution to the development of neurodegenerative diseases. However, the precise mechanisms underlying Pb-induced neurological dysfunction remain elusive. This study aimed to investigate the role of oxidative stress and the autophagy-related P62/kelch like ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in neuronal impairment caused by Pb.

Methods

By employing both in vivo and in vitro approaches, we explored the involvement of the P62/Nrf2/Keap1 pathway in Pb-induced neurotoxicity.

Results

Our findings demonstrated that Pb exposure triggers excessive production of reactive oxygen species (ROS), upregulates Keap1 protein expressions, promotes Nrf2 degradation, and inhibits expression of antioxidant proteins such as heme Oxygenase-1 (HO-1) and glutathione peroxidase (GPx), resulting in oxidative damage in neurons. Furthermore, we observed that the autophagy protein P62 disrupts the normal autophagy process by interacting with the Nrf2/Keap1 axis, leading to an accumulation of Tau, a protein associated with Alzheimer's disease (AD), ultimately resulting in neurodegeneration. However, treatment with the antioxidant N-acetylcysteine, Nrf2 activator Artemisitene, and autophagy activator Rapamycin attenuated these detrimental changes.

Conclusion

The P62/Nrf2/Keap1 pathway mediates Pb-induced neuronal dysfunction and highlights its potential as a therapeutic target for mitigating the neurodegenerative effects associated with Pb exposure.

背景铅(Pb)暴露被认为对神经退行性疾病的发展有贡献。然而,铅诱导的神经功能障碍的确切机制仍然难以捉摸。本研究旨在探讨氧化应激及自噬相关的P62/kelch样ECH-associated protein 1 (Keap1)/Nuclear factor erythroid 2-related factor 2 (Nrf2)通路在铅所致神经元损伤中的作用。方法采用体内和体外两种方法,探讨P62/Nrf2/Keap1通路在铅诱导的神经毒性中的作用。结果Pb暴露可引起活性氧(ROS)过量产生,上调Keap1蛋白表达,促进Nrf2降解,抑制血红素氧化酶-1 (HO-1)和谷胱甘肽过氧化物酶(GPx)等抗氧化蛋白的表达,导致神经元氧化损伤。此外,我们观察到自噬蛋白P62通过与Nrf2/Keap1轴相互作用破坏正常的自噬过程,导致Tau(一种与阿尔茨海默病(AD)相关的蛋白)的积累,最终导致神经退行性变。然而,用抗氧化剂n -乙酰半胱氨酸、Nrf2激活剂青蒿素和自噬激活剂雷帕霉素治疗可以减轻这些有害的变化。结论P62/Nrf2/Keap1通路介导铅诱导的神经元功能障碍,并强调其作为减轻铅暴露相关神经退行性效应的治疗靶点的潜力。
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引用次数: 0
期刊
CNS Neuroscience & Therapeutics
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