Brain Research Bulletin最新文献_第8页

miR-219 ameliorates myelin impairment and cognitive function deficits in the early stage of MCAO/R rats miR-219可改善早期MCAO/R大鼠的髓磷脂损伤和认知功能缺陷。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-16 DOI: 10.1016/j.brainresbull.2025.111692

Wenxiu Li , Jianhua Jiang , Yizhen Weng , Lulu Zhang , Quanquan Zhang , Xinyi He , Xiang Li, Sr , Xiang Tang

MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs). However, its role in myelin damage and cognitive dysfunction during acute cerebral ischemia is not well understood. In this study, we used the MCAO/R rat model to investigate the mechanistic involvement of miR-219. Our results show that miR-219 alleviates cognitive dysfunction induced by MCAO/R. The agonist group showed a reduced time to locate the platform in the water maze, while the antagonist group showed an increased time compared to the solvent control. Additionally, miR-219 reduced myelin damage, as demonstrated by Luxol Fast Blue (LFB) staining, which indicated substantial hippocampal demyelination repair in the agonist group, whereas the antagonist group exhibited aggravated demyelination. Electron microscopy revealed enhanced myelin sheath regeneration and increased thickness in the agonist group, while the antagonist group displayed fewer and thinner myelin sheaths. Furthermore, miR-219 regulated OPC maturation, with more CNPase-positive cells in the agonist group and fewer in the antagonist group than the solvent control. In NG2 staining, the agonist group had fewer positive cells, while the antagonist group had more. miR-219 also decreased Lingo-1 expression, leading to reduced levels of AKT, RhoA, and mTOR in the downstream signaling pathway. These findings suggest that activating the miR-219–Lingo-1 signaling pathway during ischemia-reperfusion could offer a potential therapeutic approach for improving myelin damage and alleviating cognitive dysfunction in cerebral ischemia.

MicroRNAs （miRNAs）是髓鞘形成和认知功能的关键调节因子，其中miR-219对少突胶质前体细胞（OPCs）的分化和成熟尤为重要。然而，其在急性脑缺血时髓磷脂损伤和认知功能障碍中的作用尚不清楚。在这项研究中，我们使用MCAO/R大鼠模型来研究miR-219的机制参与。我们的研究结果表明miR-219可以缓解MCAO/R诱导的认知功能障碍。与溶剂对照组相比，激动剂组在水迷宫中定位平台的时间缩短，而拮抗剂组在水迷宫中定位平台的时间增加。此外，Luxol Fast Blue （LFB）染色显示，miR-219减少了髓鞘损伤，这表明激动剂组海马脱髓鞘修复明显，而拮抗剂组脱髓鞘恶化。电镜显示激动剂组髓鞘再生增强，厚度增加，而拮抗剂组髓鞘数量减少，厚度变薄。此外，miR-219调节OPC成熟，与溶剂对照相比，激动剂组cnpase阳性细胞较多，拮抗剂组cnpase阳性细胞较少。NG2染色中，激动剂组阳性细胞较少，而拮抗剂组阳性细胞较多。miR-219也降低了Lingo-1的表达，导致下游信号通路中AKT、RhoA和mTOR的水平降低。这些发现表明，在缺血-再灌注过程中激活miR-219-Lingo-1信号通路可能为改善脑缺血髓磷脂损伤和减轻认知功能障碍提供潜在的治疗途径。

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引用次数: 0

Disrupted brain network topology and structural-functional decoupling in chronic post-stroke aphasia 慢性脑卒中后失语症的脑网络拓扑结构和结构-功能解耦。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-16 DOI: 10.1016/j.brainresbull.2025.111691

Guihua Xu , Yongsheng Wu , Rui Zhu , Junyu Qu , Wenwen Xu , Jiaxiang Xin , Dawei Wang

Objective

Language impairments in post-stroke aphasia (PSA) relate to reorganizations of brain structural and functional networks. While anomalies in multiple single network parameters are increasingly reported, structural-functional (S-F) coupling has not yet been explored in PSA.

Methods

A total of 52 patients with PSA and 55 age-, sex-, and education-matched normal controls (NCs) were recruited. Firstly, structural connectivity (SC) and functional connectivity (FC) networks were constructed using diffusion kurtosis imaging (DKI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. Subsequently, graph theoretical analysis was used to evaluate the global and nodal topological properties, followed by multiscale S-F coupling calculations.

Finally, partial correlation analysis was applied to investigate the relationships among the network topological properties, S-F coupling, and the western aphasia battery (WAB) scores in patients with PSA.

Results

Compared to NCs, PSA patients showed disrupted SC global topology: reduced global efficiency (Eglob), local efficiency (Eloc), clustering coefficient (Cp), and increased characteristic path length (Lp). No significant FC global differences emerged. Nodal SC properties were widely decreased, while FC exhibited hemispheric asymmetry with decreases in the left hemisphere and increases in the right. PSA patients had reduced whole-brain S-F coupling and decoupling in limbic (LN), default mode (DMN), somatomotor (SMN), and frontoparietal (FPN) networks. Notably, FPN S-F coupling was positively correlated with the aphasia quotient (AQ) of the WAB.

Conclusion

This study reveals asymmetric disruption of network topology properties and multiscale S-F decoupling in patients with PSA, highlighting the potential of S-F coupling in the FPN as a neuroimaging marker for predicting language recovery.

目的：脑卒中后失语症的语言障碍与脑结构和功能网络的重组有关。虽然多个单一网络参数的异常越来越多地被报道，但结构-功能（S-F）耦合尚未在PSA中进行探索。方法：共招募了52例PSA患者和55例年龄、性别和教育程度相匹配的正常对照（nc）。首先，利用扩散峰度成像（DKI）和静息状态功能磁共振成像（rs-fMRI）分别构建结构连接网络（SC）和功能连接网络（FC）。随后，利用图论分析评估了整体和节点拓扑特性，并进行了多尺度S-F耦合计算。最后，应用偏相关分析探讨PSA患者网络拓扑特性、S-F耦合与西部失语电池（WAB）评分之间的关系。结果：与nc相比，PSA患者的SC全局拓扑结构被破坏：全局效率（Eglob）、局部效率（Eloc）、聚类系数（Cp）降低，特征路径长度（Lp）增加。未出现显著的FC全球差异。SC节点的性质普遍降低，而FC表现出半球不对称，左半球减少，右半球增加。PSA患者在边缘（LN）、默认模式（DMN）、躯体运动（SMN）和额顶叶（FPN）网络中的全脑S-F耦合和解耦减少。值得注意的是，FPN - S-F耦合与WAB的失语商（AQ）呈正相关。结论：本研究揭示了PSA患者网络拓扑特性的不对称破坏和多尺度S-F解耦，突出了FPN中S-F耦合作为预测语言恢复的神经影像学标志物的潜力。

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引用次数: 0

Neural damage and inflammation in myotonic dystrophy type 1: Longitudinal analysis of serum NFL, GFAP, and IL-6 1型强直性肌营养不良的神经损伤和炎症：血清NFL、GFAP和IL-6的纵向分析。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-15 DOI: 10.1016/j.brainresbull.2025.111688

Joana Garmendia , Garazi Labayru , Ainhoa Alberro , Laura Martins-Almeida , David Otaegui , Pablo Iruzubieta , Adolfo Lopez de Munain , Andone Sistiaga

Introduction

Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disease affecting the central nervous system (CNS). Blood-based biomarkers such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) offer potential as non-invasive indicators of CNS dysfunction and/or inflammation. However, their longitudinal dynamics and clinical relevance in DM1 remain unclear. Additionally, sex-related differences in these biomarkers are poorly understood. This study aimed to investigate NFL, GFAP, and IL-6 serum levels in patients with DM1, examine sex-differences, track changes over four years, and explore associations with genetic, muscular, cognitive, and neuroimaging outcomes.

Method

Retrospective data from 70 DM1 patients and 54 healthy controls (HC) were analyzed. Longitudinal data were available for 68 participants (39 DM1, 29 HC). Biomarkers were measured using the ELLA immunoassay. DM1 patients had data on genetic, muscular, cognitive and structural brain outcomes. Analyses were adjusted for age.

Results

NFL and IL-6 levels were significantly higher in DM1 patients compared to HC, while GFAP levels did not differ. Male DM1 patients exhibited higher NFL and IL-6 levels compared to females. No significant longitudinal changes were observed over a four-year period. NFL and IL-6 levels correlated with larger genetic expansions and poorer cognitive performance.

Discussion

NFL and IL-6 may reflect neural damage and systemic inflammation in DM1 and could serve as biomarkers of cognitive dysfunction. However, their limited longitudinal sensitivity suggests longer follow-up is needed to evaluate their utility for disease monitoring.

1型肌强直性营养不良症（DM1）是一种累及中枢神经系统（CNS）的进行性多系统疾病。基于血液的生物标志物，如神经丝轻链（NFL）、胶质纤维酸性蛋白（GFAP）和白细胞介素-6 (IL-6)，提供了作为中枢神经系统功能障碍和/或炎症的非侵入性指标的潜力。然而，它们在DM1中的纵向动态和临床相关性尚不清楚。此外，这些生物标志物的性别相关差异尚不清楚。本研究旨在调查DM1患者的NFL、GFAP和IL-6血清水平，检查性别差异，追踪四年的变化，并探讨其与遗传、肌肉、认知和神经影像学结果的关系。方法：回顾性分析70例DM1患者和54例健康对照（HC）的资料。68名参与者（39名DM1, 29名HC）的纵向数据可用。采用ELLA免疫分析法测定生物标志物。DM1患者有基因、肌肉、认知和大脑结构方面的数据。分析根据年龄进行了调整。结果：DM1患者的NFL和IL-6水平明显高于HC，而GFAP水平无差异。男性DM1患者的NFL和IL-6水平高于女性。在四年的时间里没有观察到明显的纵向变化。NFL和IL-6水平与较大的遗传扩展和较差的认知表现相关。讨论：NFL和IL-6可能反映DM1的神经损伤和全身性炎症，可以作为认知功能障碍的生物标志物。然而，它们有限的纵向敏感性表明，需要更长的随访时间来评估它们在疾病监测中的效用。

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引用次数: 0

Cycloastragenol protected hippocampal CA1 neurons by regulating redox homeostasis and alleviated cognitive impairment following cerebral ischemia-reperfusion 环黄芪醇通过调节脑缺血再灌注后海马CA1神经元的氧化还原稳态，减轻脑缺血再灌注后认知功能障碍。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-15 DOI: 10.1016/j.brainresbull.2025.111689

Su Gao , Shihui Zhu , Tianyi Qu , Jiahui Zou , Lida Yin , Xuesong Wang , Xiaokun Yin , Lin Tong , Wei Li

Objective

This study investigated the neuroprotective effects and mechanisms of cycloastragenol (CAG) on oxidative stress and neurological function in cerebral ischemia-reperfusion injury (CIRI) and oxygen-glucose deprivation/reoxygenation (OGD/R) models.

Methods

In vivo, rats were given oral CAG daily for 28 days before CIRI induction. Cerebral infarction and hippocampal injury were assessed using TTC, Nissl, and HE staining. Neurological scores, morris water maze, grip strength tests, and brain water content were used to evaluate functional outcomes. Oxidative stress was determined by biochemical assays, DHE staining, and transmission electron microscopy, while Western blotting was performed to measure neuroprotective proteins. In vitro, primary neurons were treated with CAG and subjected to OGD/R. Cell viability was tested by CCK-8 assay, apoptosis and mitochondrial membrane potential were analyzed by flow cytometry, ROS levels were quantified, and MDA, SOD, and GSH were measured biochemically. Western blot further evaluated BDNF and NeuN expression to confirm in vivo findings.

Results

In vivo, CAG reduced infarct volume and edema, improved neurological deficits, preserved the structural integrity of neurons in the hippocampal CA1 region. CAG also promoted motor function recovery, markedly reduced MDA levels, increased SOD and GSH activity, and upregulated BDNF and NeuN expression. In vitro, CAG enhanced cell viability in the OGD/R model, reduced apoptosis, restored mitochondrial membrane potential, and significantly suppressed oxidative stress induced by ischemia-reperfusion.

Conclusion

CAG effectively alleviated injury caused by cerebral and cellular ischemia-reperfusion by maintaining redox homeostasis, inhibiting oxidative stress, and promoting the expression of neuroprotective proteins, demonstrating promising neuroprotective potential.

目的：研究环黄芪醇（CAG）对脑缺血再灌注损伤（CIRI）和氧葡萄糖剥夺/再氧化（OGD/R）模型氧化应激和神经功能的保护作用及其机制。方法：活体大鼠在CIRI诱导前每天口服CAG，持续28 d。采用TTC、Nissl、HE染色评估脑梗死及海马损伤情况。神经学评分、Morris水迷宫、握力测试和脑含水量用于评估功能结果。氧化应激通过生化试验、DHE染色、透射电镜检测，免疫印迹法检测神经保护蛋白。在体外，用CAG处理原代神经元并进行OGD/R。CCK-8法检测细胞活力，流式细胞术检测细胞凋亡和线粒体膜电位，定量测定ROS水平，生化测定MDA、SOD和GSH水平。Western blot进一步检测BDNF和NeuN的表达以证实体内结果。结果：在体内，CAG可减少梗死体积和水肿，改善神经功能缺损，保持海马CA1区神经元结构完整性。CAG还能促进运动功能恢复，显著降低MDA水平，增加SOD和GSH活性，上调BDNF和NeuN表达。CAG在体外增强OGD/R模型细胞活力，减少细胞凋亡，恢复线粒体膜电位，显著抑制缺血再灌注引起的氧化应激。结论：CAG通过维持氧化还原稳态、抑制氧化应激、促进神经保护蛋白的表达，有效减轻脑缺血再灌注损伤，具有良好的神经保护潜力。

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引用次数: 0

Reversal of auditory cortical hyperexcitability and restoration of synaptic plasticity balance by GluN1-mediated photobiomodulation in noise-induced tinnitus 噪声性耳鸣中glun1介导的光生物调节对听觉皮质高兴奋性的逆转和突触可塑性平衡的恢复。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-15 DOI: 10.1016/j.brainresbull.2025.111685

Zhixin Zhang , Xinmiao Xue , Dongdong He , Peng Liu , Chi Zhang , Yvke Jiang , Shuhan Lv , Li Wang , Hanwen Zhou , Weidong Shen , Shiming Yang , Fangyuan Wang

Glutamate receptors regulate neuronal excitability and drive synaptic plasticity in the auditory cortex (AC), with aberrant activation or dysfunction contributing to tinnitus pathogenesis. Photobiomodulation (PBM) exerts sustained modulatory effects on neural activity and behavioral responses across species, including humans. However, its therapeutic potential and mechanisms in noise-induced tinnitus remain unexplored. Here, we developed a noninvasive low-irradiance PBM device to target the AC of animal models, investigating near-infrared light mechanisms for reversing cortical hyperexcitability and restoring synaptic plasticity. In noise-exposed tinnitus models without significant neuronal loss, we observed abnormally elevated GluN1 activation and increased synaptic structural complexity compared to non-tinnitus or sham-exposed controls. Tinnitus models were subjected to PBM interventions with varying parameters (irradiance power: 20/40/80 mW/cm²; exposure duration: 300/600 s). Therapeutic efficacy was validated through auditory brainstem response (ABR), gap-prepulse inhibition of acoustic startle (GPIAS), and prepulse inhibition (PPI) behavioral assays. Fluorescence microscopy of brain sections quantified c-Fos/GluN1 co-localization to image activated NMDARs, while Nissl staining assessed PBM safety across parameters. Phosphoproteomic profiling explored mechanistic pathways, with neuronal morphological changes visualized via Golgi staining and transmission electron microscopy. To confirm GluN1’s pivotal role in auditory cognition, we engineered transgenic mice with GluN1 overexpression or knockdown. GluN1-overexpressing mice exhibited tinnitus-like behaviors at specific frequencies, whereas GluN1-deficient tinnitus models showed aberrant behaviors due to impaired auditory cognition. Our findings delineate noise-induced tinnitus mechanisms and PBM-mediated regulation of neuronal excitability and structural plasticity, establishing an irradiance-duration optimization framework for clinical translation.

谷氨酸受体调节听觉皮层（AC）的神经元兴奋性并驱动突触可塑性，其异常激活或功能障碍与耳鸣发病有关。光生物调节（PBM）对包括人类在内的物种的神经活动和行为反应具有持续的调节作用。然而，其治疗噪声性耳鸣的潜力和机制仍未被探索。在这里，我们开发了一种无创低辐照PBM装置，以动物模型的AC为目标，研究近红外光逆转皮层高兴奋性和恢复突触可塑性的机制。在没有明显神经元损失的噪声暴露耳鸣模型中，我们观察到与非耳鸣或假暴露对照组相比，GluN1激活异常升高，突触结构复杂性增加。耳鸣模型接受不同参数的PBM干预（辐照功率：20/40/80mW/cm²；照射时间：300/600s）。通过听觉脑干反应（ABR）、声惊间隙-脉冲前抑制（GPIAS）和脉冲前抑制（PPI）行为测试验证治疗效果。脑切片的荧光显微镜定量了c-Fos/GluN1共定位到图像激活的NMDARs，而尼氏染色评估了PBM各参数的安全性。通过高尔基染色和透射电镜观察神经元形态学变化，磷蛋白组学分析探索了机制途径。为了证实GluN1在听觉认知中的关键作用，我们设计了GluN1过表达或敲低的转基因小鼠。glun1过表达小鼠在特定频率下表现出耳鸣样行为，而glun1缺陷耳鸣模型由于听觉认知受损而表现出异常行为。我们的研究结果描述了噪声诱发耳鸣的机制和pbm介导的神经元兴奋性和结构可塑性的调节，为临床翻译建立了一个辐照-持续时间优化框架。

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引用次数: 0

Peripheral CD200R signaling: A critical regulator of post-stroke inflammation in aged mice 外周CD200R信号：老龄小鼠脑卒中后炎症的关键调节因子。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-13 DOI: 10.1016/j.brainresbull.2025.111686

Conelius Ngwa, Afzal Misrani, Yan Xu, Jingjing Wang, Rodney Ritzel, Fudong Liu

The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16–19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then subjected to a 45-min transient middle cerebral artery occlusion (MCAO). At three days post-stroke, flow cytometry, ELISA, and immunohistochemistry (IHC) were used to assess immune responses. Infarct volumes and neurobehavioral deficits were also evaluated. We found that T cell infiltration into the brain was significantly greater in KO-to-GFP (central CD200R signaling) compared to GFP-to-KO (peripheral CD200R signaling) mice. KO-to-GFP mice also exhibited significantly higher levels of pro-inflammatory cytokines IL-1β and TNF-α in the ischemic brain than GFP-to-KO chimeras. Correspondingly, KO-to-GFP mice showed significantly larger brain infarct volumes and worse neurobehavior deficits compared to GFP-to-KO chimeras. Together, these findings indicate that the peripheral (not the central) CD200R signaling plays a critical role in controlling post-stroke immune responses and delineating ischemic injury.

缺血性脑卒中的免疫反应受到内源性抑制途径的影响，该途径界定了脑卒中后的炎症。其中，CD200与其受体（CD200R）之间的相互作用因其在调节各种中枢神经系统（CNS）疾病的神经炎症中的作用而越来越被认识。在本研究中，我们使用老年骨髓嵌合（BMC）小鼠（16-19月龄）研究了中央（脑）和外周CD200R信号在急性缺血性卒中中的作用。这些嵌合体是通过将CD200R敲除（KO）、绿色荧光蛋白（GFP）或野生型（WT）供体小鼠的骨髓移植到受照射的受体小鼠中，然后进行45分钟的短暂性大脑中动脉闭塞（MCAO）而产生的。脑卒中后3天，采用流式细胞术、ELISA和免疫组织化学（IHC）评估免疫反应。梗塞体积和神经行为缺陷也被评估。我们发现，与GFP-to-KO（外周CD200R信号）小鼠相比，KO-to-GFP（中枢CD200R信号）小鼠的T细胞浸润到大脑的程度明显更高。与gfp - ko嵌合体相比，KO-to-GFP小鼠在缺血脑中的促炎细胞因子IL-1β和TNF-α水平也显著提高。相应地，与gfp - ko嵌合体相比，ko - gfp嵌合体小鼠表现出更大的脑梗死体积和更严重的神经行为缺陷。总之，这些发现表明外周（而非中枢）CD200R信号在控制脑卒中后免疫反应和描绘缺血性损伤中起关键作用。

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引用次数: 0

Effects of repetitive transcranial magnetic stimulation on apoptosis and MAPK/PI3K-AKT signaling pathways in rats with spinal cord injury 反复经颅磁刺激对脊髓损伤大鼠细胞凋亡及MAPK/PI3K-AKT信号通路的影响

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-13 DOI: 10.1016/j.brainresbull.2025.111687

Qingqin Xu , Junhong Su , Qian Lei , Jinxiu Liu , Jing Wang , Mengyu Yang , Juan Song , Hemu Chen , Jianwei Lu

Background

Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive neuromodulation technique, but its mechanisms in spinal cord injury (SCI) remain unclear. This study investigated the effects and potential mechanisms of rTMS on motor recovery in SCI rats.

Methods

A rat SCI model was established using the modified Allen's method. rTMS treatment was initiated on postoperative Day 2 and administered daily for 56 days. Bioinformatics analysis was first conducted to identify SCI-related genes and signaling pathways. Western blotting, immunofluorescence staining, TUNEL assay, NeuN staining, motor evoked potential (MEP) measurement, hematoxylin-eosin staining, and Basso-Beattie-Bresnahan (BBB) score were performed to evaluate molecular and functional outcomes.

Results

Bioinformatics analysis identifies MAPK-, PI3K/AKT-, and Bcl-2-related genes as potentially involved in SCI pathology. Western blotting reveals that rTMS is associated with lower levels of p-JNK, p-p38 MAPK, Bax, and caspase-3, and with higher levels of p-ERK, p-PI3K, p-AKT, and Bcl-2 (P < 0.001). Immunoﬂuorescence staining shows that rTMS is accompanied by reduced p-JNK and p-p38 MAPK positive cells and increased p-ERK, p-PI3K and p-AKT positive cells (P < 0.001). TUNEL and NeuN staining further suggest reduced neuronal apoptosis in the injured spinal cord. Behavioral and electrophysiological assessments show that rTMS is associated with shorter MEP latencies, higher MEP amplitudes, reduced spinal tissue damage, attenuated muscle atrophy, and improved BBB score (P < 0.001).

Conclusion

rTMS is associated with improvements in motor function and anti-apoptotic molecular changes in SCI rats, possibly via modulation of MAPK and PI3K/AKT signaling pathways, including upregulation of Bcl-2 and downregulation of Bax and caspase-3.

背景：重复经颅磁刺激（rTMS）是一种很有前途的无创神经调节技术，但其在脊髓损伤（SCI）中的机制尚不清楚。本研究探讨了rTMS对脊髓损伤大鼠运动恢复的影响及其可能机制。方法：采用改良Allen法建立大鼠脊髓损伤模型。术后第2天开始rTMS治疗，每天给药56天。首先进行了生物信息学分析，以确定sci相关基因和信号通路。Western blotting、免疫荧光染色、TUNEL染色、NeuN染色、运动诱发电位（MEP）测定、苏木素-伊红染色和Basso-Beattie-Bresnahan （BBB）评分来评估分子和功能结果。结果：生物信息学分析发现MAPK-、PI3K/AKT-和bcl -2相关基因可能参与了脊髓损伤的病理过程。Western blotting结果显示，rTMS与p-JNK、p-p38 MAPK、Bax和caspase-3水平降低有关，与p-ERK、p-PI3K、p-AKT和Bcl-2水平升高有关(结论：rTMS与脊髓损伤大鼠运动功能改善和抗凋亡分子变化有关，可能通过调节MAPK和PI3K/AKT信号通路，包括上调Bcl-2和下调Bax和caspase-3。

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引用次数: 0

Comparison of epilepsy mouse models induced by kainic acid through different administration routes 不同给药途径kainic酸致痫小鼠模型的比较。

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-12 DOI: 10.1016/j.brainresbull.2025.111684

Li-Wei Xing , Chen Yang , Wenxuan Tang , Yongjie Deng , Wen-Xu Wang , Jia-Hui Guo , Xin-Yi Wang , Run-Chen Fang , Jian Guan , Jing Cang , Shi-Bin Li

Sleep disruption associated with epilepsy is frequently observed in clinical practice. Various epilepsy animal models including the widely-used chemoconvulsant kainic acid (KA) have been developed to unveil the mechanisms underlying this life-threatening central disorder and improve sleep management. However, a systematic comparison of epilepsy models induced through different KA administration routes (intrahippocampal, IH, vs. intraperitoneal, IP) remains lacking. In this study, we monitored the dynamic changes of sleep/wake architecture, the development of epilepsy, and performed histological mapping of brain regions potentially implicated in epileptogenesis. We observed a more severe disruption of sleep architecture associated with seizures perpetuating for a longer time in the IHKA group. IHKA induced a more robust epilepsy pattern with significant increases of wakefulness and reductions of sleep during the acute phase. A chronic epilepsy model was developed in the IHKA group, but not in the IPKA group. Both IHKA and IPKA groups developed NREM sleep fragmentation during the chronic phase. Isolated spikes induced by IHKA appeared more frequently than those induced by IPKA at all time points, and gradually declined before stabilization around day 14 post-administration. Both IPKA and IHKA induced elevated c-Fos expression within 3 h after the drug administration as compared to their controls. Pearson correlation analyses of c-Fos expression across brain regions revealed that the IHKA group exhibited more correlations among multiple brain regions, reflecting a broader network of activated regions compared with the IPKA group after local KA exposure. Therefore, IHKA creates a more robust epilepsy mouse model characterized by a more fragmented sleep pattern, more seizures, and more isolated spikes.

在临床实践中经常观察到与癫痫相关的睡眠中断。包括广泛使用的化学惊厥药kainic acid （KA）在内的各种癫痫动物模型已经被开发出来，以揭示这种危及生命的中枢疾病的机制，并改善睡眠管理。然而，通过不同KA给药途径（海马内，IH和腹腔内，IP）诱导的癫痫模型的系统比较仍然缺乏。在这项研究中，我们监测了睡眠/觉醒结构的动态变化，癫痫的发展，并对可能与癫痫发生有关的大脑区域进行了组织学定位。我们观察到，在IHKA组中，与癫痫发作持续时间较长相关的睡眠结构破坏更为严重。IHKA诱导了一种更强健的癫痫模式，在急性期显著增加清醒和减少睡眠。IHKA组建立慢性癫痫模型，IPKA组未建立慢性癫痫模型。IHKA组和IPKA组在慢性期均出现NREM睡眠断裂。IHKA诱导的离体尖峰在各时间点出现的频率均高于IPKA，并在给药后第14天左右逐渐下降，趋于稳定。与对照组相比，IPKA和IHKA在给药后3小时内均诱导c-Fos表达升高。跨脑区c-Fos表达的Pearson相关分析显示，与IPKA组相比，局部KA暴露后，IHKA组在多个脑区之间表现出更多的相关性，反映了更广泛的激活区域网络。因此，IHKA创建了一个更健壮的癫痫小鼠模型，其特征是更碎片化的睡眠模式，更多的癫痫发作和更多的孤立尖峰。

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引用次数: 0

Linking VR performance to cognitive ability: The significance of ACC-PCL connectivity in aging populations VR表现与认知能力的联系：老年人群ACC-PCL连接的意义

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-10 DOI: 10.1016/j.brainresbull.2025.111681

Zhen Gu , Jing Cao , Zhiqiang Wu , Ling Yue

Background

Neuropsychological tests provide standardized cognitive assessment but have limited ecological validity. Virtual reality (VR) creates immersive environments, better reflecting real-world cognitive performance. Although impaired VR performance correlates with early cognitive decline, its neural mechanisms remain unclear in non-demented elders. This study investigates fMRI biomarkers linked to VR performance to identify neural predictors of cognitive decline.

Methods

24 non-demented older adults, including cognitively normal (CN) and mild cognitive impairment (MCI), completed baseline resting-state fMRI and immersive VR tasks combining physical and cognitive demands (dog walking, mountain climbing, drone protection). VR performance score (VRS) was quantified via entropy weight method. We analyzed relationships between VRS, neuropsychological scores, and resting-state functional connectivity (FC).

Results

VRS significantly correlated with MoCA visuospatial/executive scores (p = 0.015). Whole-brain FC analysis revealed a strong association between VRS and FC between the left anterior cingulate cortex (ACC) and left paracentral lobule (PCL) in the overall sample (adjusted p = 1.94 × 10⁻⁶), present in CN but absent in MCI. Stepwise regression confirmed this FC as the significant VRS predictor in CN (R² = 0.599, p < 0.001).

Conclusion

Immersive VR performance reflects visuospatial/executive function and is predicted by left ACC-PCL connectivity, serving as a neuroimaging biomarker for real-world cognition that complements traditional assessments. Practically, this biomarker requires validation in larger longitudinal cohorts.

背景：神经心理学测试提供标准化的认知评估，但生态效度有限。虚拟现实（VR）创造了沉浸式环境，更好地反映了现实世界的认知表现。尽管VR表现受损与早期认知能力下降有关，但其在非痴呆老年人中的神经机制尚不清楚。本研究调查了与VR表现相关的fMRI生物标志物，以确定认知能力下降的神经预测因子。方法24名认知正常（CN）和轻度认知障碍（MCI）的非痴呆老年人完成基线静息状态fMRI和结合身体和认知需求的沉浸式VR任务（遛狗、爬山、无人机保护）。采用熵权法对虚拟现实性能评分进行量化。我们分析了VRS、神经心理学评分和静息状态功能连通性（FC）之间的关系。结果vrs与MoCA视觉空间/执行得分显著相关（p = 0.015）。全脑FC分析显示，在整个样本中，左前扣带皮层（ACC）和左中央旁小叶（PCL）之间的VRS和FC之间存在很强的关联（调整p = 1.94 × 10⁻26），这种关联在CN中存在，但在MCI中不存在。逐步回归证实该FC是CN的显著VRS预测因子（R²= 0.599,p <； 0.001）。结论沉浸式VR表现反映了视觉空间/执行功能，并通过左ACC-PCL连接预测，可作为现实世界认知的神经成像生物标志物，补充传统评估。实际上，这种生物标志物需要在更大的纵向队列中进行验证。

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引用次数: 0

A multimodal fusion framework reveals the heterogeneity of basal ganglia atrophy and its molecular mechanisms in temporal lobe epilepsy 一个多模态融合框架揭示了颞叶癫痫基底神经节萎缩的异质性及其分子机制

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin

Pub Date : 2025-12-09 DOI: 10.1016/j.brainresbull.2025.111682

Guiming Weng , Xiaochuan Fu , Cuimi Luo , Qin Zhou , Huoyou Hu , Bailing Qin , Binghua Lv , Zirong Chen , Jinou Zheng

The heterogeneity of basal ganglia (BG) atrophy in temporal lobe epilepsy (TLE) has not been fully elucidated. This study employed a multimodal fusion framework to examine the potential heterogeneity of BG atrophy among TLE patients. 89 patients diagnosed with TLE were recruited. Structural magnetic resonance imaging (sMRI), resting - state functional magnetic resonance imaging (fMRI), consensus clustering (CC), and neuroimaging - transcriptomic approaches were integrated to explore the structural and functional alterations in the BG and their molecular mechanisms. Canonical correlation analysis (CCA) was employed to investigate the associations between MRI features and clinical characteristics. An individualized prediction model was constructed to facilitate clinical decision-making. CC identified a significant subgroups of BG atrophy in TLE: widespread BG atrophy (TLE-Cluster1, TLE-C1). In TLE-C1, the functional connectivity between the BG and cortical regions associated with sensation, emotion, and memory was notably enhanced. These patients additionally exhibited more severe cognitive impairment as well as higher degrees of anxiety and depression. Transcriptomic analysis established a connection between the heterogeneity of BG atrophy and specific gene expression patterns that were enriched in biological processes such as synaptic function, neurostructural development, and learning and memory. Further analyses uncovered a positive correlation between the gray matter volume of BG and cognitive performance. A classifier based on a Neural Network (NNET) predicted cognitive function with an area under curve (AUC) of 0.983. This study characterizes BG atrophy heterogeneity in TLE, its molecular mechanisms, and clinical relevance, offering insights for personalized diagnosis and management.

颞叶癫痫（TLE）基底神经节（BG）萎缩的异质性尚未完全阐明。本研究采用多模式融合框架来研究TLE患者BG萎缩的潜在异质性。招募了89名诊断为TLE的患者。结合结构磁共振成像（sMRI）、静息状态功能磁共振成像（fMRI）、共识聚类（CC）和神经成像-转录组学方法来探索BG的结构和功能改变及其分子机制。采用典型相关分析（CCA）探讨MRI特征与临床特征之间的关系。构建个性化预测模型，为临床决策提供依据。CC在TLE中发现了一个重要的BG萎缩亚组：广泛的BG萎缩（TLE- cluster1, TLE- c1）。在TLE-C1中，BG与感觉、情绪和记忆相关的皮质区域之间的功能连通性显著增强。这些患者还表现出更严重的认知障碍以及更高程度的焦虑和抑郁。转录组学分析证实了BG萎缩的异质性与特定基因表达模式之间的联系，这些基因表达模式在突触功能、神经结构发育、学习和记忆等生物过程中丰富。进一步的分析揭示了BG灰质体积与认知能力之间的正相关关系。基于神经网络（NNET）的分类器预测认知功能的曲线下面积（AUC）为0.983。本研究揭示了TLE患者BG萎缩的异质性、分子机制和临床相关性，为个性化诊断和治疗提供了新的思路。

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引用次数: 0