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Cognitive Performance and Quality of Life in Relapsing-Remitting Multiple Sclerosis: A BICAMS- and PROs-Based Study in a Mexican Public Hospital. 复发缓解型多发性硬化症患者的认知表现和生活质量:一项墨西哥公立医院BICAMS和pros研究
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-19 DOI: 10.3390/neurosci6030066
María Fernanda Castillo-Zuñiga, Rodolfo Manuel Roman-Guzman, Idefonso Rodríguez-Leyva

Background: Cognitive impairment (CI) is a common and disabling symptom in patients with relapsing-remitting multiple sclerosis (RRMS), potentially emerging at any stage, including preclinical phases. Despite its impact on quality of life, CI often goes unrecognized, as clinical follow-up typically focuses on motor and sensory symptoms. Validated tools, such as the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and patient-reported outcomes (PROs), should be integrated into routine evaluations beyond the Expanded Disability Status Scale (EDSS).

Objective: The objective of this study was to evaluate cognitive impairment and quality of life in patients with RRMS using the BICAMS and PROs.

Methods: This cross-sectional, descriptive study included patients with RRMS under follow-up at a tertiary hospital in San Luis Potosí, Mexico. Participants underwent cognitive screening with the BICAMS battery and completed the MSQoL-54 (quality of life), FSMC (fatigue), and MSIS-29 (functional impact) scales. Statistical analyses included ANOVA, the Kruskal-Wallis test, and Pearson correlations.

Results: Nineteen patients were evaluated (73.7% female, mean age 36.5 ± 8.9 years). BICAMS results showed variable cognitive performance, with no significant differences across treatment groups for processing speed (p = 0.222), verbal memory (p = 0.082), or visuospatial memory (p = 0.311). A significant correlation was found between verbal and visuospatial memory (r = 0.668, p = 0.002). Total quality of life differed significantly across treatments (F = 8.007, p = 0.029), with a strong correlation between overall quality of life and general health perception (r = 0.793, p < 0.001). Fatigue and MSIS scores showed no association with treatment.

Conclusions: Cognitive impairment is common in RRMS and can be detected using brief assessment tools, such as the BICAMS. Incorporating cognitive screening and PROs into clinical practice is essential to guide comprehensive management.

背景:认知障碍(CI)是复发-缓解型多发性硬化症(RRMS)患者常见的致残症状,可能出现在任何阶段,包括临床前阶段。尽管CI对生活质量有影响,但由于临床随访通常侧重于运动和感觉症状,因此CI往往未被发现。经过验证的工具,如国际多发性硬化症简短认知评估(BICAMS)和患者报告的结果(PROs),应该纳入常规评估,而不是扩展残疾状态量表(EDSS)。目的:本研究的目的是使用BICAMS和PROs评估RRMS患者的认知功能障碍和生活质量。方法:这项横断面描述性研究纳入了在墨西哥圣路易斯Potosí三级医院随访的RRMS患者。参与者使用BICAMS电池进行认知筛选,并完成MSQoL-54(生活质量)、FSMC(疲劳)和MSIS-29(功能影响)量表。统计分析包括方差分析、Kruskal-Wallis检验和Pearson相关性。结果:共纳入19例患者,其中女性73.7%,平均年龄(36.5±8.9岁)。BICAMS结果显示不同的认知表现,处理速度(p = 0.222)、言语记忆(p = 0.082)和视觉空间记忆(p = 0.311)在治疗组之间没有显著差异。语言记忆与视觉空间记忆之间存在显著相关(r = 0.668, p = 0.002)。不同治疗组的总体生活质量差异显著(F = 8.007, p = 0.029),总体生活质量与总体健康感知之间有很强的相关性(r = 0.793, p < 0.001)。疲劳和MSIS评分与治疗无关。结论:认知障碍在RRMS中很常见,可以通过BICAMS等简单的评估工具检测到。将认知筛查和pro纳入临床实践对指导综合管理至关重要。
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引用次数: 0
Meta-Analysis of Gene Expression in Bulk-Processed Post-Mortem Spinal Cord from ALS Patients and Normal Controls. 肌萎缩侧索硬化症(ALS)患者和正常人死后大量加工脊髓中基因表达的meta分析。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-16 DOI: 10.3390/neurosci6030065
William R Swindell

Amyotrophic lateral sclerosis (ALS) is characterized by upper and lower motor neuron failure and poor prognosis. This study performed a meta-analysis of gene expression datasets that compared bulk-processed post-mortem spinal cord from ALS and control (CTL) patients. The analysis included 569 samples (454 ALS, 115 CTL) from 348 individuals (262 ALS, 86 CTL). Patterns of differential expression bias, related to mRNA abundance, gene length and GC content, were discernable from individual studies but attenuated by meta-analysis. A total of 213 differentially expressed genes (DEGs) were identified (144 ALS-increased, 69 ALS-decreased). ALS-increased DEGs were most highly expressed by microglia and associated with MHC class II, immune response and leukocyte activation. ALS-decreased DEGs were abundantly expressed by mature oligodendrocytes (e.g., the MOL5 phenotype) and associated with myelin production, plasma membrane and sterol metabolism. Comparison to spatial transcriptomics data showed that DEGs were prominently expressed in white matter, with increased DEG expression strongest in the ventral/lateral white matter. These results highlight white matter as the spinal cord region most strongly associated with the shifts in mRNA abundance observed in bulk-processed tissues. These shifts can be explained by attrition of mature oligodendrocytes and an ALS-emergent microglia phenotype that is partly shared among neurodegenerative conditions.

肌萎缩性侧索硬化症(ALS)以上下运动神经元功能衰竭和预后不良为特征。这项研究对基因表达数据集进行了荟萃分析,比较了ALS和对照(CTL)患者的大量处理的死后脊髓。分析包括来自348个人(262个ALS, 86个CTL)的569个样本(454个ALS, 115个CTL)。与mRNA丰度、基因长度和GC含量相关的差异表达偏倚模式在个别研究中是可识别的,但通过荟萃分析减弱了这种偏倚。共鉴定出213个差异表达基因(DEGs),其中144个als增高,69个als降低。als增加的deg在小胶质细胞中最高表达,并与MHC II类、免疫反应和白细胞活化相关。als降低的DEGs在成熟少突胶质细胞(例如MOL5表型)中大量表达,并与髓磷脂生成、质膜和固醇代谢有关。与空间转录组学数据的比较显示,DEG在白质中显著表达,其中DEG在腹侧/外侧白质中表达最强。这些结果突出了白质作为脊髓区域与大量加工组织中观察到的mRNA丰度变化最密切相关。这些变化可以通过成熟少突胶质细胞的磨损和als出现的小胶质细胞表型来解释,这种表型在神经退行性疾病中部分共享。
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引用次数: 0
Beyond Cognition: Cognitive Re-Education's Impact on Quality of Life and Psychological Well-Being in People with Multiple Sclerosis-A Narrative Review. 认知之外:认知再教育对多发性硬化症患者生活质量和心理健康的影响——述评
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-15 DOI: 10.3390/neurosci6030064
Nicola Manocchio, Chiara Moriano, Anna D'Amato, Michela Bossa, Calogero Foti, Ugo Nocentini

Cognitive impairment is a prevalent and disabling feature of multiple sclerosis (MS), significantly impacting patients' quality of life (QoL) and psychological well-being. Despite its clinical relevance, there are currently no approved pharmacological treatments for cognitive deficits in MS, highlighting the need for effective non-pharmacological interventions. This narrative review explores evidence from studies evaluating the efficacy of cognitive re-education (CR) approaches (including traditional, group-based, computer-assisted, virtual reality, and innovative methods such as music therapy) on cognitive and QoL outcomes in people with MS. The findings demonstrate that while CR consistently influences cognitive domains such as memory, attention, and executive function, its effects on QoL are more variable and often depend on intervention type, duration, and individual patient characteristics. Notably, integrative approaches like virtual reality and music therapy show promising results in enhancing both cognitive performance and psychosocial well-being. Several studies report that cognitive gains are accompanied by improvements in mental health and functional QoL, particularly when interventions are tailored to individual needs and delivered within multidisciplinary frameworks. However, some interventions yield only limited or transient QoL benefits, underlining the importance of personalized, goal-oriented strategies that address both cognitive and psychosocial dimensions. Further research is needed to optimize intervention strategies and clarify the mechanisms linking cognitive and QoL outcomes.

认知障碍是多发性硬化症(MS)的常见致残特征,严重影响患者的生活质量(QoL)和心理健康。尽管具有临床意义,但目前还没有批准的药物治疗多发性硬化症的认知缺陷,这突出了有效的非药物干预的必要性。本文对认知再教育(CR)方法(包括传统的、基于群体的、计算机辅助的、虚拟现实的和创新的方法,如音乐疗法)对ms患者认知和生活质量结果的有效性的研究证据进行了综述。研究结果表明,虽然CR持续影响认知领域,如记忆、注意力和执行功能,但其对生活质量的影响更加多变,通常取决于干预类型。持续时间和个体患者特征。值得注意的是,像虚拟现实和音乐疗法这样的综合方法在提高认知能力和社会心理健康方面都显示出有希望的结果。一些研究报告称,认知能力的提高伴随着心理健康和功能性生活质量的改善,特别是当干预措施根据个人需求量身定制并在多学科框架内实施时。然而,一些干预措施只能产生有限的或短暂的生活质量效益,这强调了个性化、目标导向的策略的重要性,这些策略可以同时解决认知和社会心理方面的问题。需要进一步的研究来优化干预策略,明确认知和生活质量结果之间的联系机制。
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引用次数: 0
Combined Cognitive and Exercise Training Enhances Muscular Strength and Endurance: A Pilot Study. 认知和运动相结合的训练增强肌肉力量和耐力:一项初步研究。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-14 DOI: 10.3390/neurosci6030063
Alexandru Rautu, Jesús Díaz-García, Christopher Ring

Background: Combined cognitive and exercise training improves exercise endurance, including submaximal muscular endurance. Its effects on maximal muscular strength have yet to be determined. Accordingly, we tested the effects of combined training on muscular strength (one repetition maximum, 1RM) and endurance (as many repetitions as possible, AMRAP).

Methods: Resistance-trained adults (five males, three females) completed ten sessions (four testing, six training) over 4 weeks. In each testing session, they were assessed for bench press 1RM before they completed AMRAP at 50% of initial 1RM. In each training session, they performed five bench press sets (five repetitions at 80% current 1RM), with each set followed by a hard 5 min cognitive task (Time-Load Dual-Back or Color Multi-Source Interference). Ratings of perceived exertion (RPE) were averaged to provide a session RPE. At the end of each session, participants completed a Psychomotor Fatigue Threshold Test and rated mental fatigue.

Results: ANOVAs (four testing sessions) showed that combined training increased 1RM (p < 0.001; averaging 8.0 kg or 11% from sessions 1-4) and AMRAP (p < 0.01; 5.1 repetitions or 22%). Moreover, training increased RPE (p < 0.05; 0.3 or 5%) and decreased mental fatigue ratings (p < 0.001; -1.2 or -49%) but did not affect Psychomotor Fatigue Threshold Test reaction times (p > 0.05; 2 ms or 0%).

Conclusions: A 4-week training program that combined high-intensity cognitive and resistance exercise tasks improved maximal and submaximal resistance exercise performance. This pilot study provides preliminary evidence that high-intensity combined training can enhance muscular strength and endurance.

背景:认知与运动结合训练可提高运动耐力,包括亚极限肌肉耐力。它对最大肌肉力量的影响还有待确定。因此,我们测试了联合训练对肌肉力量(最多1次重复,1RM)和耐力(尽可能多的重复,AMRAP)的影响。方法:接受阻力训练的成年人(5名男性,3名女性)在4周内完成了10次训练(4次测试,6次训练)。在每个测试阶段,他们在完成AMRAP之前以初始1RM的50%进行卧推1RM评估。在每次训练中,他们做了五组卧推(五组重复,80%电流1RM),每组之后是一个5分钟的认知任务(时间负载双背或彩色多源干扰)。对感知运动强度评分(RPE)取平均值,得出一个疗程的RPE。在每个疗程结束时,参与者完成了一项精神运动疲劳阈值测试,并评估了精神疲劳程度。结果:方差分析(4次测试)显示联合训练增加了1RM (p < 0.001;1-4期平均8.0 kg或11%)和AMRAP (p < 0.01;5.1次重复或22%)。此外,训练提高了RPE (p < 0.05;0.3或5%),精神疲劳评分降低(p < 0.001;-1.2或-49%),但不影响精神运动疲劳阈值测试反应时间(p > 0.05;2毫秒或0%)。结论:为期4周的高强度认知和阻力训练任务相结合的训练计划提高了最大和次最大阻力运动的表现。这项初步研究提供了高强度联合训练可以增强肌肉力量和耐力的初步证据。
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引用次数: 0
Do Pain and Autonomic Regulation Share a Common Central Compensatory Pathway? A Meta-Analysis of HRV Metrics in Pain Trials. 疼痛和自主调节有共同的中枢代偿通路吗?疼痛试验中HRV指标的meta分析。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-05 DOI: 10.3390/neurosci6030062
Marianna Daibes, Bassel Almarie, Maria Fernanda Andrade, Giovanna de Paula Vidigal, Nadine Aranis, Anna Gianlorenco, Carlos Bandeira de Mello Monteiro, Prateek Grover, David Sparrow, Felipe Fregni

Background: Chronic pain is closely associated with dysregulation of the autonomic nervous system, often reflected by reduced heart rate variability (HRV). While observational studies have demonstrated this association, the extent to which pain interventions modulate HRV and the impact of individual factors on HRV changes remain unclear.

Objective: To evaluate the impact of pain interventions on HRV parameters through meta-analysis of randomized controlled trials (RCTs), and to examine whether intervention type and individual factors such as body mass index (BMI) moderate HRV responses.

Methods: We conducted a systematic review of 23 RCTs and a meta-analysis of 21 RCTs (1262 subjects) involving patients with acute and chronic pain. HRV outcomes were extracted pre- and post-intervention. Both between-group (active vs. sham/control) and one-group (pre-post within active group) analyses were performed for time-domain indices-standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of successive normal-to-normal intervals > 50 ms (pNN50)-and frequency-domain indices-high-frequency (HF) and low-frequency (LF) components. Meta-regressions tested moderators including BMI, age, and pain phenotype. The protocol was registered in PROSPERO (CRD42023448264).

Results: Twenty-three RCTs involving 1262 participants with a wide range of pain conditions were included. Meta-analysis of time-domain HRV parameters showed a trend toward improvement: SDNN (g = 0.435, p = 0.059) approached significance, while RMSSD (g = 0.361, p = 0.099) and pNN50 (g = 0.222, p = 0.548) showed smaller, non-significant effects. Frequency-domain analysis revealed a significant moderate reduction in the LF/HF ratio (g = -0.378, p = 0.003), suggesting a shift toward parasympathetic dominance. HF and LF showed small, non-significant changes. One-group meta-analysis confirmed significant improvements in vagally mediated HRV, with large effects for RMSSD (g = 1.084, p < 0.001) and HF (g = 0.622, p < 0.001), and a moderate effect for SDNN (g = 0.455, p = 0.004). Meta-regression identified BMI as a significant moderator: higher BMI was associated with attenuated improvements in HF and RMSSD and a slight shift toward sympathetic predominance. Conclusions: Pain interventions can significantly modulate autonomic function, as reflected in HRV improvements, particularly in vagally mediated indices. These effects are influenced by patient characteristics such as BMI. HRV may serve as a valuable biomarker for both treatment efficacy and autonomic recovery in pain management. In this context, HRV highlights its role as a biomarker for pain dysregulation and compensatory failure, reflecting shared top-down modulation between nociception and autonomic regulation.

背景:慢性疼痛与自主神经系统的失调密切相关,通常反映为心率变异性(HRV)的降低。虽然观察性研究已经证明了这种关联,但疼痛干预调节HRV的程度以及个体因素对HRV变化的影响仍不清楚。目的:通过随机对照试验(RCTs)的meta分析,评价疼痛干预对HRV参数的影响,并探讨干预类型和个体因素如体重指数(BMI)是否对HRV反应有调节作用。方法:我们对涉及急性和慢性疼痛患者的23项随机对照试验进行了系统评价,并对21项随机对照试验(1262名受试者)进行了荟萃分析。在干预前和干预后提取HRV结果。对时域指标-正常到正常间隔的标准差(SDNN)、连续差异的均方根(RMSSD)、连续正常到正常间隔bbb50 ms的百分比(pNN50)和频域指标-高频(HF)和低频(LF)成分进行了组间分析和一组(活动组的前后)分析。meta回归测试了包括BMI、年龄和疼痛表型在内的调节因子。该协议在PROSPERO (CRD42023448264)中注册。结果:纳入了23项随机对照试验,涉及1262名具有各种疼痛状况的参与者。时间域HRV参数meta分析显示有改善趋势:SDNN (g = 0.435, p = 0.059)接近显著,RMSSD (g = 0.361, p = 0.099)和pNN50 (g = 0.222, p = 0.548)影响较小,无显著性。频域分析显示,LF/HF比值有显著的中度降低(g = -0.378, p = 0.003),表明向副交感神经主导转变。HF和LF变化不大,不显著。一组荟萃分析证实迷走神经介导的HRV有显著改善,RMSSD (g = 1.084, p < 0.001)和HF (g = 0.622, p < 0.001)有较大效果,SDNN有中等效果(g = 0.455, p = 0.004)。meta回归发现BMI是一个显著的调节因素:较高的BMI与HF和RMSSD的改善减弱以及向交感神经优势的轻微转变相关。结论:疼痛干预可以显著调节自主神经功能,这反映在HRV的改善上,特别是迷走神经介导的指数。这些效果受患者特征(如BMI)的影响。HRV可以作为疼痛管理中治疗效果和自主神经恢复的有价值的生物标志物。在这种情况下,HRV突出了其作为疼痛失调和代偿性失败的生物标志物的作用,反映了伤害感觉和自主调节之间共同的自上而下的调节。
{"title":"Do Pain and Autonomic Regulation Share a Common Central Compensatory Pathway? A Meta-Analysis of HRV Metrics in Pain Trials.","authors":"Marianna Daibes, Bassel Almarie, Maria Fernanda Andrade, Giovanna de Paula Vidigal, Nadine Aranis, Anna Gianlorenco, Carlos Bandeira de Mello Monteiro, Prateek Grover, David Sparrow, Felipe Fregni","doi":"10.3390/neurosci6030062","DOIUrl":"10.3390/neurosci6030062","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain is closely associated with dysregulation of the autonomic nervous system, often reflected by reduced heart rate variability (HRV). While observational studies have demonstrated this association, the extent to which pain interventions modulate HRV and the impact of individual factors on HRV changes remain unclear.</p><p><strong>Objective: </strong>To evaluate the impact of pain interventions on HRV parameters through meta-analysis of randomized controlled trials (RCTs), and to examine whether intervention type and individual factors such as body mass index (BMI) moderate HRV responses.</p><p><strong>Methods: </strong>We conducted a systematic review of 23 RCTs and a meta-analysis of 21 RCTs (1262 subjects) involving patients with acute and chronic pain. HRV outcomes were extracted pre- and post-intervention. Both between-group (active vs. sham/control) and one-group (pre-post within active group) analyses were performed for time-domain indices-standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (RMSSD), and percentage of successive normal-to-normal intervals > 50 ms (pNN50)-and frequency-domain indices-high-frequency (HF) and low-frequency (LF) components. Meta-regressions tested moderators including BMI, age, and pain phenotype. The protocol was registered in PROSPERO (CRD42023448264).</p><p><strong>Results: </strong>Twenty-three RCTs involving 1262 participants with a wide range of pain conditions were included. Meta-analysis of time-domain HRV parameters showed a trend toward improvement: SDNN (g = 0.435, <i>p</i> = 0.059) approached significance, while RMSSD (g = 0.361, <i>p</i> = 0.099) and pNN50 (g = 0.222, <i>p</i> = 0.548) showed smaller, non-significant effects. Frequency-domain analysis revealed a significant moderate reduction in the LF/HF ratio (g = -0.378, <i>p</i> = 0.003), suggesting a shift toward parasympathetic dominance. HF and LF showed small, non-significant changes. One-group meta-analysis confirmed significant improvements in vagally mediated HRV, with large effects for RMSSD (g = 1.084, <i>p</i> < 0.001) and HF (g = 0.622, <i>p</i> < 0.001), and a moderate effect for SDNN (g = 0.455, <i>p</i> = 0.004). Meta-regression identified BMI as a significant moderator: higher BMI was associated with attenuated improvements in HF and RMSSD and a slight shift toward sympathetic predominance. <b>Conclusions:</b> Pain interventions can significantly modulate autonomic function, as reflected in HRV improvements, particularly in vagally mediated indices. These effects are influenced by patient characteristics such as BMI. HRV may serve as a valuable biomarker for both treatment efficacy and autonomic recovery in pain management. In this context, HRV highlights its role as a biomarker for pain dysregulation and compensatory failure, reflecting shared top-down modulation between nociception and autonomic regulation.</p>","PeriodicalId":74294,"journal":{"name":"NeuroSci","volume":"6 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sleep Deprivation in Rats Causes Dissociation of the Synaptic NMDA Receptor/D1 Dopamine Receptor Heterocomplex. 睡眠剥夺导致大鼠突触NMDA受体/D1多巴胺受体异复合体的分离。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-07-05 DOI: 10.3390/neurosci6030061
Natalia Kiknadze, Nana Narmania, Maia Sepashvili, Tamar Barbakadze, Elene Zhuravliova, Tamar Shetekauri, Nino Tkemaladze, Nikoloz Oniani, David Mikeladze

Glutamate and dopamine receptors play a crucial role in regulating synaptic plasticity throughout the sleep-wake cycle. These receptors form various heterocomplexes in synaptic areas; however, the role of this protein interactome in sleep-wake cycles remains unclear. Co-immunoprecipitation experiments were conducted to observe the complexation of the NMDA glutamate receptor (NMDAR) subunits GluN2A and GluN2B, metabotropic glutamate receptors mGluR1/5, and dopamine receptors (D1R and D2R) with the scaffold protein Homer in the synaptic membranes of the hippocampus after six hours of sleep deprivation (SD) in rats. Our findings indicate that the level of Homer in the GluN2A/mGluR1/D1R interactome decreased during SD, while the content of Homer remained unchanged in the GluN2B/mGluR1/D2R heterocomplex. Moreover, Homer immunoprecipitated a reduced amount of inositol trisphosphate receptor (IP3R) in the microsomal and synaptic fractions, confirming the dissociation of the ternary supercomplex Homer/mGluR1/IP3R during SD. Additionally, our findings indicate that SD increases the synaptic content of the AMPA receptor (AMPAR) subunit GluA1. Unlike AMPAR, NMDAR subunits in synaptic membranes do not undergo significant changes. Furthermore, the G-to-F actin ratio decreases during SD. Changes in the assembly of actin filaments occur due to the dephosphorylation of cofilin. These results suggest that SD causes the dissociation of the GluN2A/mGluR1/D1R/Homer/IP3R heterocomplex in synaptic and endoplasmic membranes.

在整个睡眠-觉醒周期中,谷氨酸和多巴胺受体在调节突触可塑性方面起着至关重要的作用。这些受体在突触区形成各种异质复合物;然而,这种蛋白质相互作用组在睡眠-觉醒周期中的作用尚不清楚。采用共免疫沉淀实验,观察6小时睡眠剥夺(SD)后大鼠海马突触膜内NMDA谷氨酸受体(NMDAR)亚基GluN2A和GluN2B、代谢性谷氨酸受体mGluR1/5、多巴胺受体(D1R和D2R)与支架蛋白Homer的络合作用。我们的研究结果表明,在SD期间,GluN2A/mGluR1/D1R互作组中Homer的含量下降,而GluN2B/mGluR1/D2R杂交体中Homer的含量保持不变。此外,Homer免疫沉淀了微粒体和突触部分肌醇三磷酸受体(IP3R)的减少量,证实了在SD期间三元超复合物Homer/mGluR1/IP3R的解离。此外,我们的研究结果表明,SD增加了AMPA受体(AMPAR)亚基GluA1的突触含量。与AMPAR不同,突触膜中的NMDAR亚基不会发生显著变化。此外,SD期间G-to-F肌动蛋白比值降低。肌动蛋白丝的组装发生变化是由于cofilin的去磷酸化。这些结果表明,SD导致GluN2A/mGluR1/D1R/Homer/IP3R异复合体在突触和内质膜上的解离。
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引用次数: 0
Derivation of Novel Imaging Biomarkers of Neonatal Brain Injury Using Bedside Diffuse Optical Tomography: Protocol for a Prospective Feasibility Study. 利用床边弥漫性光学断层扫描提取新生儿脑损伤的新型成像生物标志物:一项前瞻性可行性研究方案。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-06-30 DOI: 10.3390/neurosci6030060
Sabrina Mastroianni, Anagha Vinod, Naiqi G Xiao, Heather Johnson, Lehana Thabane, Qiyin Fang, Ipsita Goswami

Prognostication of neurodevelopmental outcomes for neonates with hypoxic-ischemic encephalopathy (HIE) is primarily reliant on structural assessment using conventional brain magnetic resonance imaging in the clinical setting. Diffuse optical tomography (DOT) can provide complementary information on brain function at the bedside, further enhancing prognostic accuracy. The predictive accuracy and generalizability of DOT-based neuroimaging markers are unknown. This study aims to test the feasibility of prospectively recruiting and retaining neonates for 12 months in a larger study that investigates the prognostic utility of DOT-based biomarkers of HIE. The study will recruit 25 neonates with HIE over one year and follow them beyond NICU discharge at 6 and 12 months of age. Study subjects will undergo resting-state DOT measurement within 7 days of life for a 30-45-min period without sedation. A customized neonatal cap with 10 sources and eight detectors per side will be used to quantify cortical functional connectivity and to generate brain networks using MATLAB-based software (version 24.2). The Ages and Stages Questionnaires-3rd edition will be used for standardized developmental assessments at follow-up. This feasibility study will help refine the design and sample-size calculation for an adequately powered larger study that determines the clinical utility of DOT-based neuroimaging in perinatal brain injury.

新生儿缺氧缺血性脑病(HIE)的神经发育预后主要依赖于临床常规脑磁共振成像的结构评估。弥漫性光学断层扫描(DOT)可以在床边提供关于脑功能的补充信息,进一步提高预后的准确性。基于dot的神经影像学标记的预测准确性和普遍性尚不清楚。本研究的目的是在一项更大的研究中测试前瞻性招募和保留新生儿12个月的可行性,该研究调查了基于dot的HIE生物标志物的预后效用。该研究将招募25名患有HIE的新生儿超过一年,并在他们6个月和12个月大时随访至新生儿重症监护病房出院。研究对象将在生命的7天内进行静息状态DOT测量,持续30-45分钟,无镇静。一个定制的新生儿帽,每侧有10个源和8个检测器,将用于量化皮质功能连接,并使用基于matlab的软件(版本24.2)生成大脑网络。年龄和阶段问卷-第三版将用于随访时的标准化发展评估。这项可行性研究将有助于完善设计和样本量的计算,以进行更大规模的研究,以确定基于dot的神经成像在围产期脑损伤中的临床应用。
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引用次数: 0
β2-Microglobulin Regulates Extracellular Matrix Dynamics During Peripheral Nerve Injury. β2-微球蛋白调节周围神经损伤时细胞外基质动力学。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-06-29 DOI: 10.3390/neurosci6030059
Eiki Shirasawa, Kentaro Uchida, Kenji Onuma, Gen Inoue, Koji Eshima, Masashi Satoh, Masayuki Miyagi, Yoji Toyomura, Akira Norisugi, Masashi Takaso

Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8+ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3+CD4+ and CD3+CD8+ T-cell populations increased by day 7 post-injury. While CD3+CD4+ T-cell expansion occurred in both groups, a significant increase in CD3+CD8+ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury-prior to substantial T-cell accumulation-revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM-receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8+ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M's function beyond classical immune roles.

周围神经损伤引发了一系列复杂的级联反应,包括免疫反应、细胞外基质(ECM)重塑和神经元修复。虽然β2-微球蛋白(B2M)因其在MHC i类介导的抗原呈递和CD8+ t细胞分化中的作用而闻名,但其对非免疫过程的潜在贡献仍未得到充分探讨。在这项研究中,我们利用野生型和B2M缺陷型(B2M- ko)小鼠的慢性收缩损伤(CCI)模型研究了B2M在周围神经再生中的作用。采用流式细胞术、RNA测序(RNA-seq)和定量PCR (qPCR)评估损伤后t细胞亚群动态和基因表达。流式细胞术分析显示,损伤后第7天CD3+CD4+和CD3+CD8+ t细胞群增加。两组小鼠均出现CD3+CD4+ T细胞扩增,但仅在野生型小鼠中观察到CD3+CD8+ T细胞显著增加。损伤后3天的RNA-seq分析显示,在大量t细胞积累之前,B2M-KO小鼠的ECM相关基因显著下调,包括胶原、基质相关蛋白和其他关键的ECM成分。KEGG分析发现ecm受体相互作用、PI3K-Akt和TGF-β信号通路受到抑制。qPCR证实B2M-KO小鼠中Thbs1表达降低。这些发现表明,在早期神经修复过程中,B2M在调节ECM动力学和再生信号方面发挥着关键的、不依赖CD8+ t细胞的作用,扩展了B2M功能的概念框架,超出了经典的免疫作用。
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引用次数: 0
Electrodiagnostic Evaluation of Meralgia Paresthetica. 触感异常痛的电诊断评价。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-06-22 DOI: 10.3390/neurosci6030058
Jernej Avsenik, Simon Podnar

Background: We aimed to determine the utility of different electrodiagnostic (EDx) methods in diagnosing meralgia paresthetica (MP).

Methods: Twenty-nine MP patients and 26 controls were included. Sensory nerve action potential (SNAP) and somatosensory evoked potential (SEP) of the lateral femoral cutaneous nerve (LFCN) and tibial SEPs were measured bilaterally.

Results: At least one LFCN SNAP was unobtainable in 18 patients (62%) and two controls (8%). In all remaining 11 patients, SNAPs were abnormal at least unilaterally. By contrast, LFCN SEPs were recorded bilaterally in all subjects and were abnormal in 16 patients (sensitivity 48%). Patients' tibial SEP latency was significantly larger than that of controls (p < 0.001).

Conclusions: LFCN NCSs are superior to SEP in the evaluation of MP. However, SEP studies may be useful in old (>60 years) and obese subjects with unobtainable LFCN SNAP. Longer tibial SEP points to subclinical neuropathy in MP patients predisposed to LFCN entrapment.

背景:我们的目的是确定不同的电诊断(EDx)方法在诊断痛觉异常(MP)中的效用。方法:选取MP患者29例,对照组26例。测量双侧股外侧皮神经(LFCN)的感觉神经动作电位(SNAP)、体感诱发电位(SEP)和胫骨SEP。结果:18例患者(62%)和2例对照组(8%)中至少1例LFCN SNAP无法获得。在其余11例患者中,snap至少单侧异常。相比之下,所有受试者均记录双侧LFCN sep, 16例患者异常(敏感性48%)。患者胫骨SEP潜伏期明显大于对照组(p < 0.001)。结论:LFCN NCSs对MP的评价优于SEP。然而,SEP研究可能对老年(60 - 60岁)和无法获得LFCN SNAP的肥胖受试者有用。较长的胫骨SEP指向易发生LFCN卡压的MP患者的亚临床神经病变。
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引用次数: 0
14th Panhellenic Conference on Alzheimer's Disease and the 6th Mediterranean Conference on Neurodegenerative Diseases, 13 February-16 February, Thessaloniki, Greece. 第14届泛希腊阿尔茨海默病会议和第6届地中海神经退行性疾病会议,2月13日至16日,希腊塞萨洛尼基。
IF 2 Q3 CLINICAL NEUROLOGY Pub Date : 2025-06-20 DOI: 10.3390/neurosci6030057
Magda Tsolaki

At the 14th Panhellenic Conference on Alzheimer's Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: onset, diagnosis, progression, and eventual outcome. Fighting alongside him are researchers, doctors, psychologists, biologists, chemists, pharmacists, nurses, trainers, physiotherapists, speech therapists, occupational therapists, electrical engineers, architects, and other scientists, even actors and musicians, who aim to prevent and cure the disease, limit its progression, and improve the quality of life of those affected by it. Among them, their caregivers stand out as the most dedicated companions. In a collection of abstracts that reflects the work of all of the above, we capture the results of our biennial scientific meeting, which, thanks to them, is constantly evolving in a promising way.

在第14届泛希腊阿尔茨海默病会议和第6届地中海神经退行性疾病会议上,我们经历了一次激动人心的旅程,跟随患者经历了神经退行性疾病的各个阶段:发病、诊断、进展和最终结果。与他并肩作战的有研究人员、医生、心理学家、生物学家、化学家、药剂师、护士、培训师、物理治疗师、语言治疗师、职业治疗师、电气工程师、建筑师和其他科学家,甚至还有演员和音乐家,他们的目标是预防和治疗这种疾病,限制其发展,并改善受其影响的人的生活质量。其中,他们的照顾者是最专注的伴侣。在一个反映上述所有工作的摘要集合中,我们捕捉了我们两年一次的科学会议的结果,由于他们,它不断地以一种有希望的方式发展。
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引用次数: 0
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