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Stressed minds, altered strategies: Acute stress impairs proactive control in table tennis athletes. 紧张的头脑,改变的策略:急性压力损害乒乓球运动员的主动控制。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-04 DOI: 10.1016/j.brainresbull.2026.111766
Lin Xu, Ziyi Peng, Jie Lian, Xinxin Gong, Yongcong Shao, Mengfei Han, Fubin Jiao

Background: Intense stress greatly affects athletes' mental state and performance, and cognitive control, which is vital for handling unexpected situations and maintaining peak performance. Although previous research has shown that acute stress can impact different aspects of cognitive control, the exact mechanisms and effects are still debated. This study aimed to investigate how acute stress impacts proactive and reactive control in table tennis players, providing new insights into the intricate role of stress in athletes' cognitive control.

Methods: Acute stress was induced in 25 male table tennis athletes using the Maastricht Acute Stress Task (MAST). Behavioral and electroencephalogram (EEG) data were recorded before and after acute stress exposure. The EEG data included both resting-state and task-related recordings. Functional connectivity analysis was conducted on the resting-state EEG data. Event-related potential (ERP) analysis was conducted on the task-related EEG data recorded during the AX-Continuous Performance Task (AX-CPT).

Results: The behavioral results showed similar reaction times in table tennis athletes before and after acute stress, with AY trials showing significantly higher accuracy. The ERP results revealed a decrease in contingent negative variation (CNV) amplitude and increased N2 component but no significant difference was observed between the P3b and P3a components before and after acute stress. Functional connectivity analysis showed that acute stress activated the visual network and enhanced functional connectivity with multiple brain regions.

Conclusion: Acute stress induces large-scale activation of visual and salience networks while affecting the two modes of cognitive control, with reactive control predominating over proactive control. The weakening of proactive control by acute stress affected response preparation rather than pre-attention and stimuli processing, while the enhancement of reactive control resulted increased detection and monitoring of conflicting information. These findings shed light on how acute stress induces a neurocognitive shift in athletes, contributing to the advancement of the Dual Mechanisms of Cognitive Control (DMC) framework. This shift highlights the critical balance between proactive and reactive control under stress, offering valuable insights for developing interventions that optimize athletes' performance under high-pressure conditions.

背景:强烈的压力会极大地影响运动员的精神状态和表现,以及认知控制,这对于处理突发情况和保持最佳表现至关重要。尽管先前的研究表明,急性压力会影响认知控制的不同方面,但确切的机制和影响仍存在争议。本研究旨在探讨急性应激对乒乓球运动员主动控制和反应控制的影响,为了解应激在运动员认知控制中的复杂作用提供新的见解。方法:采用马斯特里赫特急性应激实验对25名男子乒乓球运动员进行急性应激诱导。记录急性应激前后的行为和脑电图(EEG)数据。脑电图数据包括静息状态和任务相关记录。对静息状态脑电数据进行功能连通性分析。对连续表现任务(AX-CPT)中记录的任务相关脑电数据进行事件相关电位(ERP)分析。结果:乒乓球运动员在急性应激前和应激后的反应时间相似,AY试验的准确性明显更高。ERP结果显示,急性应激前后P3b和P3a的随机负变异(CNV)幅度减小,N2成分增加,但P3b和P3a成分之间无显著差异。功能连通性分析表明,急性应激激活了视觉网络,增强了大脑多个区域的功能连通性。结论:急性应激诱导视觉网络和显著性网络大规模激活,同时影响两种认知控制模式,反应性控制优于主动控制。急性应激对主动控制的减弱影响反应准备而非前注意和刺激加工,而反应性控制的增强导致对冲突信息的发现和监测增加。这些发现揭示了急性应激如何诱导运动员的神经认知转变,促进了认知控制双重机制(DMC)框架的发展。这种转变强调了压力下主动控制和被动控制之间的关键平衡,为开发优化运动员在高压条件下表现的干预措施提供了有价值的见解。
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引用次数: 0
The Use of Whole-Brain Network Topology and Weighted Gene Coexpression Analysis to Identify Potential Imaging and Molecular Markers for Glioma Grading. 利用全脑网络拓扑和加权基因共表达分析识别神经胶质瘤分级的潜在成像和分子标记。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-04 DOI: 10.1016/j.brainresbull.2026.111765
Yue Yuan, Xun-Heng Wang

Background: Glioblastoma (GBM), which is characterized by high invasiveness and spatial heterogeneity, poses significant challenges in terms of prognosis and treatment. In this study, whole-brain network topology was combined with gene coexpression analysis to identify potential imaging and molecular markers for glioma grading, shifting the research focus from localized tumor lesions to the interaction mechanisms between the nervous system and gliomas.

Methods: In this study, data from open-access datasets, including glioma imaging data from the Brain Tumor Segmentation Challenge (BraTS'2019), data on glioma-related genes from BrainBase, and whole-brain transcriptomic data from the Allen Human Brain Atlas, were used. Wavelet-based features were extracted separately from T1- and T2-weighted magnetic resonance (MR) images and integrated to construct individualized structural brain networks with the aim of characterizing glioma heterogeneity. LASSO regression was applied to perform feature selection and extract the representative structural network metrics. We evaluated the effectiveness of the derived network features in glioma grading from this novel perspective via four classification models: support vector machine (SVM), random forest, logistic regression, and XGBoost. Furthermore, weighted gene coexpression network analysis (WGCNA) was employed to link disruptions in structural connectivity between high- and low-grade gliomas with the expression patterns of glioma-related genes, thereby identifying potential molecular markers associated with tumor progression.

Results: The results demonstrated that the whole-brain network-based grading approach achieved test-set AUC values above 0.85 across all four models, with the SVM and logistic regression models showing the best performance (AUC = 0.87). Additionally, the high invasiveness of high-grade gliomas may lead to the decoupling and reorganization of structural network modules. Protein kinase C beta (PRKCB) has been identified as a potential molecular biomarker associated with glioma grade.

Conclusions: Wavelet-based individualized brain structural networks have been proposed for glioma grading models, resulting in novel imaging and molecular markers for cancer neuroscience.

背景:胶质母细胞瘤(Glioblastoma, GBM)具有高侵袭性和空间异质性的特点,在预后和治疗方面提出了重大挑战。本研究将全脑网络拓扑结构与基因共表达分析相结合,确定神经胶质瘤分级的潜在影像学和分子标志物,将研究重点从局部肿瘤病变转移到神经系统与神经胶质瘤的相互作用机制。方法:在本研究中,使用了来自开放获取数据集的数据,包括来自脑肿瘤分割挑战(BraTS'2019)的胶质瘤成像数据、来自BrainBase的胶质瘤相关基因数据和来自Allen人脑图谱的全脑转录组数据。基于小波的特征分别从T1和t2加权磁共振(MR)图像中提取,并整合以构建个性化的脑结构网络,目的是表征胶质瘤的异质性。采用LASSO回归进行特征选择,提取具有代表性的结构网络指标。我们通过支持向量机(SVM)、随机森林、逻辑回归和XGBoost四种分类模型,从这个新颖的角度评估了衍生网络特征在胶质瘤分级中的有效性。此外,加权基因共表达网络分析(WGCNA)被用于将高、低级别胶质瘤之间的结构连接中断与胶质瘤相关基因的表达模式联系起来,从而确定与肿瘤进展相关的潜在分子标记。结果:结果表明,基于全脑网络的评分方法在所有四种模型中均实现了0.85以上的测试集AUC值,其中SVM和逻辑回归模型表现最佳(AUC = 0.87)。此外,高级别胶质瘤的高侵袭性可能导致结构网络模块的解耦和重组。蛋白激酶C β (PRKCB)已被确定为与胶质瘤分级相关的潜在分子生物标志物。结论:基于小波的个性化脑结构网络已被提出用于胶质瘤分级模型,为癌症神经科学提供了新的成像和分子标记。
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引用次数: 0
Deep learning-based one-stop 11C-CFT and 18F-FDG dual-tracer brain PET imaging protocol for Parkinson's disease. 基于深度学习的一站式11C-CFT和18F-FDG双示踪脑PET成像方案治疗帕金森病
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-04 DOI: 10.1016/j.brainresbull.2026.111764
Xiaolin Sun, Yuan Chang, Xiaoyue Tan, Qing Zhang, Hao Sun, Shanzhen He, Fanghu Wang, Lijun Lu, Lei Jiang

This study explored using deep learning (DL) to separate short-interval staggered 11C-CFT/18F-FDG brain PET images for Parkinson's disease, aiming to reduce scan waiting time. A total of 67 patients performing 11C-CFT and 18F-FDG brain PET scans on separate days were retrospectively enrolled. A Swin UNETR model was trained to generate pseudo 18F-FDG PET images from simulated dual-tracer sum images. The simulation assumed 18F-FDG was administered at 80, 100, 120, or 200 min (∆t) after 11C-CFT injection. Compared to actual 18F-FDG images, the pseudo images showed high visual similarity across all ∆t intervals. Low average NMSE values (∼0.0004) and high average SSIM values (0.9991-0.9993) were consistently achieved across all Δt groups. Bland & Altman analysis of the whole brain region demonstrated low average SUVR bias across all Δt groups remained within ±0.001. Region-wise correlation analysis revealed strong correlations between actual and pseudo 18F-FDG images across all Δt, with slopes ranging from 0.994 to 1.001, and all R2> 0.99. SUVmean, LBR and SNR values for pseudo 18F-FDG images exhibited no statistically significant differences compared to actual 18F-FDG images (P > 0.05). Dual-tracer PET images can be effectively separated using the DL model, yielding high-quality visual and semi-quantitative results when 18F-FDG is injected immediately after the 11C-CFT PET scan, thereby reducing patient wait time, improving patient comfort, and enhancing overall clinical efficiency.

本研究探索利用深度学习(DL)分离帕金森病的短间隔交错11C-CFT/18F-FDG脑PET图像,旨在减少扫描等待时间。回顾性纳入67例患者,分别在不同天进行11C-CFT和18F-FDG脑PET扫描。训练Swin UNETR模型,从模拟的双示踪剂和图像生成伪18F-FDG PET图像。模拟假设在11C-CFT注射后,分别在80,100,120或200min(∆t)给药18F-FDG。与实际的18F-FDG图像相比,伪图像在所有∆t区间都显示出很高的视觉相似性。低平均NMSE值(~0.0004)和高平均SSIM值(0.9991-0.9993)在所有Δt组中一致实现。Bland & Altman对整个大脑区域的分析表明,在所有Δt组中,平均SUVR偏倚较低,保持在±0.001以内。区域相关分析显示,在所有Δt中,真实和伪18F-FDG图像之间存在很强的相关性,斜率范围为0.994至1.001,R2均为0.99。伪18F-FDG图像的SUVmean、LBR和SNR值与真实18F-FDG图像相比差异无统计学意义(P < 0.05)。使用DL模型可以有效分离双示踪PET图像,在11C-CFT PET扫描后立即注射18F-FDG,可以获得高质量的视觉和半定量结果,从而减少患者等待时间,提高患者舒适度,提高整体临床效率。
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引用次数: 0
Orexin dual receptor antagonist attenuates neurological deficits possibly via PI3K/Akt/mTOR pathway activation in sleep-deprived stroke rats. 食欲素双受体拮抗剂可能通过激活PI3K/Akt/mTOR通路减轻睡眠剥夺卒中大鼠的神经功能缺损。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-04 DOI: 10.1016/j.brainresbull.2026.111762
Lili Wang, Xinli Xiong, Baofeng Wang, Haiyu Li, Gang Li, Feifeng Liu

Background: Post-stroke sleep disorders are frequent complications of ischemic stroke and contribute to poor neurological recovery. Dual orexin receptor antagonists (DORAs) promote sleep via mechanisms distinct from traditional hypnotics. This study investigated whether almorexant attenuates sleep deprivation (SD)-aggravated ischemic injury in rats and explored the its potential association with PI3K/Akt/mTOR signaling pathway.

Methods: Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), and were assigned to sham, MCAO, MCAO+SD, MCAO+SD+almorexant, or MCAO+SD+estazolam. Neurological function (Zea-Longa score, open-field test), infarct volume (TTC), histopathology (H&E), neuronal apoptosis (TUNEL), and PI3K/Akt/mTOR expression (Western blot, RT-qPCR) were assessed.

Results: SD exacerbated neurological deficits after MCAO, as reflected by higher Zea-Longa scores and impaired locomotor activity. Almorexant treatment was associated with improved behavioral performance and reduced histologic injury, neuronal apoptosis in sleep-deprived MCAO rats At the molecular level, both almorexant and estazolam treatments were associated with upregulated PI3K, Akt, and mTOR expression at both protein and mRNA levels.

Conclusion: Almorexant was associated with attenuation of SD-exacerbated ischemic brain injury in rats, accompanied by alterations in PI3K/Akt/mTOR signaling, suggesting DORAs may have potential relevance for the management of post-stroke insomnia.

背景:脑卒中后睡眠障碍是缺血性脑卒中的常见并发症,导致神经系统恢复不良。双食欲素受体拮抗剂(DORAs)通过不同于传统催眠药的机制促进睡眠。本研究探讨almorexant是否能减轻睡眠剥夺(SD)加重的大鼠缺血性损伤,并探讨其与PI3K/Akt/mTOR信号通路的潜在关联。方法:雄性Sprague-Dawley大鼠经永久性大脑中动脉闭塞(MCAO)治疗,分为假手术、MCAO、MCAO+SD、MCAO+SD+almorexant、MCAO+SD+estazolam。观察大鼠神经功能(Zea-Longa评分,开野试验)、梗死体积(TTC)、组织病理学(H&E)、神经元凋亡(TUNEL)和PI3K/Akt/mTOR表达(Western blot, RT-qPCR)。结果:SD加重了MCAO后的神经功能缺损,反映在较高的Zea-Longa评分和运动活动受损上。Almorexant治疗可改善睡眠剥夺MCAO大鼠的行为表现,减少组织学损伤和神经元凋亡。在分子水平上,Almorexant和estazolam治疗均可上调PI3K、Akt和mTOR的蛋白和mRNA表达。结论:Almorexant与sd加重的大鼠缺血性脑损伤的衰减相关,并伴有PI3K/Akt/mTOR信号通路的改变,提示DORAs可能与卒中后失眠的治疗有潜在的相关性。
{"title":"Orexin dual receptor antagonist attenuates neurological deficits possibly via PI3K/Akt/mTOR pathway activation in sleep-deprived stroke rats.","authors":"Lili Wang, Xinli Xiong, Baofeng Wang, Haiyu Li, Gang Li, Feifeng Liu","doi":"10.1016/j.brainresbull.2026.111762","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2026.111762","url":null,"abstract":"<p><strong>Background: </strong>Post-stroke sleep disorders are frequent complications of ischemic stroke and contribute to poor neurological recovery. Dual orexin receptor antagonists (DORAs) promote sleep via mechanisms distinct from traditional hypnotics. This study investigated whether almorexant attenuates sleep deprivation (SD)-aggravated ischemic injury in rats and explored the its potential association with PI3K/Akt/mTOR signaling pathway.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), and were assigned to sham, MCAO, MCAO+SD, MCAO+SD+almorexant, or MCAO+SD+estazolam. Neurological function (Zea-Longa score, open-field test), infarct volume (TTC), histopathology (H&E), neuronal apoptosis (TUNEL), and PI3K/Akt/mTOR expression (Western blot, RT-qPCR) were assessed.</p><p><strong>Results: </strong>SD exacerbated neurological deficits after MCAO, as reflected by higher Zea-Longa scores and impaired locomotor activity. Almorexant treatment was associated with improved behavioral performance and reduced histologic injury, neuronal apoptosis in sleep-deprived MCAO rats At the molecular level, both almorexant and estazolam treatments were associated with upregulated PI3K, Akt, and mTOR expression at both protein and mRNA levels.</p><p><strong>Conclusion: </strong>Almorexant was associated with attenuation of SD-exacerbated ischemic brain injury in rats, accompanied by alterations in PI3K/Akt/mTOR signaling, suggesting DORAs may have potential relevance for the management of post-stroke insomnia.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111762"},"PeriodicalIF":3.7,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Niosome-encapsulated sodium butyrate enhances blood-brain barrier integrity and reduces neuroinflammation in a rat model of ischemic stroke nio质体包封丁酸钠增强缺血性脑卒中大鼠模型血脑屏障完整性并减少神经炎症。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.brainresbull.2026.111736
Nasim Naseri , Mohammad Reza Bigdeli , Fatemeh Mortazavi Moghadam , Bahram Kazemi
Ischemic stroke remains a major cause of mortality and disability worldwide, accompanied by severe inflammation and blood-brain barrier (BBB) disruption. Sodium butyrate (SB), a promising therapeutic agent, has been extensively studied for its anti-inflammatory effects in neurological disorders. However, its bioavailability is limited by low bioavailability and a short half-life. To address this challenge, SB-loaded niosome nanoparticles (NSB) were synthesized using the thin-film hydration method with a 1:1 ratio of Tween-60 and cholesterol and tested for physicochemical properties. NSB exhibited a particle size of 81.59 nm, PDI of 0.276, zeta potential of –3.36 mV, entrapment efficiency of 94.11 %, and 62.7 % reduction in cumulative release over 24 h. Also, Field-emission scanning electron microscopy (FE-SEM) confirmed the spherical morphology and polydispersity of the nanoparticles. To investigate the therapeutic efficacy of NSB, male Wistar rats were divided into four groups: sham, control, SB, and NSB. Treatments were administered intraperitoneally, followed by middle cerebral artery occlusion (MCAO). Neurobehavioral assessments, histopathological alterations, BBB permeability, biochemical factors, and relative mRNA expression of Tnf-α, Il-1β, Claudin-5, Zo-1, and Mmp-9 were measured 24 h post-reperfusion. NSB administration significantly reduced infarct volume, neurobehavioral deficits, BBB permeability, and histopathological damage compared to free SB. Additionally, NSB increased the enzyme activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde levels and mRNA expression of proinflammatory cytokines. Furthermore, NSB preserved BBB integrity by reducing Mmp-9 expression while upregulating Claudin-5 and Zo-1. These findings suggest niosomes as a promising nano-formulation to enhance SB bioavailability and neuroprotective efficacy in ischemic stroke.
缺血性脑卒中仍然是世界范围内死亡和残疾的主要原因,并伴有严重的炎症和血脑屏障(BBB)破坏。丁酸钠(SB)是一种很有前途的治疗药物,因其抗炎治疗神经系统疾病的作用而被广泛研究。然而,其生物利用度受到生物利用度低和半衰期短的限制。为了解决这一挑战,采用薄膜水化法,以1:1的tween60和胆固醇的比例合成了负载sb的纳米颗粒(NSB),并测试了其物理化学性质。NSB的粒径为81.59nm, PDI为0.276,zeta电位为-3.36mV,包封效率为94.11%,24h累积释放量减少62.7%。此外,场发射扫描电镜(FE-SEM)证实了纳米颗粒的球形形貌和多分散性。将雄性Wistar大鼠分为4组:假手术组、对照组、SB组和NSB组,观察NSB的治疗效果。治疗方法为腹腔注射,随后进行大脑中动脉闭塞(MCAO)。再灌注24小时后测量神经行为评估、组织病理学改变、血脑屏障通透性、生化因子以及Tnf-α、Il-1β、Claudin-5、Zo-1和Mmp-9的相对mRNA表达。与游离SB相比,NSB可显著降低梗死面积、神经行为缺陷、血脑屏障通透性和组织病理学损伤。此外,NSB可提高超氧化物歧化酶和谷胱甘肽过氧化物酶活性,降低丙二醛水平和促炎细胞因子mRNA表达。此外,NSB通过降低Mmp-9的表达,同时上调Claudin-5和Zo-1,从而保持血脑屏障的完整性。这些研究结果表明,纳米粒是一种很有前途的纳米制剂,可以提高SB的生物利用度和缺血性卒中的神经保护功效。
{"title":"Niosome-encapsulated sodium butyrate enhances blood-brain barrier integrity and reduces neuroinflammation in a rat model of ischemic stroke","authors":"Nasim Naseri ,&nbsp;Mohammad Reza Bigdeli ,&nbsp;Fatemeh Mortazavi Moghadam ,&nbsp;Bahram Kazemi","doi":"10.1016/j.brainresbull.2026.111736","DOIUrl":"10.1016/j.brainresbull.2026.111736","url":null,"abstract":"<div><div>Ischemic stroke remains a major cause of mortality and disability worldwide, accompanied by severe inflammation and blood-brain barrier (BBB) disruption. Sodium butyrate (SB), a promising therapeutic agent, has been extensively studied for its anti-inflammatory effects in neurological disorders. However, its bioavailability is limited by low bioavailability and a short half-life. To address this challenge, SB-loaded niosome nanoparticles (NSB) were synthesized using the thin-film hydration method with a 1:1 ratio of Tween-60 and cholesterol and tested for physicochemical properties. NSB exhibited a particle size of 81.59 nm, PDI of 0.276, zeta potential of –3.36 mV, entrapment efficiency of 94.11 %, and 62.7 % reduction in cumulative release over 24 h. Also, Field-emission scanning electron microscopy (FE-SEM) confirmed the spherical morphology and polydispersity of the nanoparticles. To investigate the therapeutic efficacy of NSB, male Wistar rats were divided into four groups: sham, control, SB, and NSB. Treatments were administered intraperitoneally, followed by middle cerebral artery occlusion (MCAO). Neurobehavioral assessments, histopathological alterations, BBB permeability, biochemical factors, and relative mRNA expression of <em>Tnf-α</em>, <em>Il-1β</em>, <em>Claudin-5</em>, <em>Zo-1</em>, and <em>Mmp-9</em> were measured 24 h post-reperfusion. NSB administration significantly reduced infarct volume, neurobehavioral deficits, BBB permeability, and histopathological damage compared to free SB. Additionally, NSB increased the enzyme activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde levels and mRNA expression of proinflammatory cytokines. Furthermore, NSB preserved BBB integrity by reducing <em>Mmp-9</em> expression while upregulating <em>Claudin-5</em> and <em>Zo-1</em>. These findings suggest niosomes as a promising nano-formulation to enhance SB bioavailability and neuroprotective efficacy in ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111736"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights Saraswata Ghrita减轻了AlCl₃-和d -半乳糖在小鼠阿尔茨海默病样模型中引起的认知缺陷:在计算机和体内的见解。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.brainresbull.2026.111742
Robin Badal , Balveer Kaur , Harvinder Singh , Poonam Sharma , Pramod Yadav , Arun Mahapatra , Shivani Ghildiyal , Ashok Kumar Patel , Lalan Kumar , Bhupesh Sharma , Pradeep Kumar Prajapati , Tanuja Nesari

Background

Alzheimer’s disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico–in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways.

Methods

SG constituents were profiled by GC–MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4 mg/kg, i.p.) + D-galactose (50 mg/kg, i.p.) for 60 days; SG (3, 6, 12 mL/kg, p.o.) or donepezil (0.5 mg/kg, i.p.) was administered on days 31–60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group).

Results

In silico, LIG_91 showed the top predicted AChE binding affinity (−8.5 kcal·mol⁻¹) and LIG_212 scored −7.8 kcal·mol⁻¹ (supportive evidence). AlCl₃+D-galactose impaired cognition (MWM day-4 ELT 85.8 ± 5.3 s; TSTQ 34.6 ± 2.2 s). SG 12 mL/kg improved MWM performance (ELT 44.1 ± 3.2 s, ∼49 % lower vs model; TSTQ 50.1 ± 2.8 s, ∼45 %higher), while donepezil produced greater improvement (ELT 26.7 ± 2.4 s, ∼69 % lower; TSTQ 58.1 ± 5.4 s, ∼68 %higher). SG 12 mL/kg reduced oxidative stress (TBARS 12.93 ± 1.58 → 8.84 ± 0.52 nM/mg, ∼32 % decrease) and improved antioxidant status (GSH 7.52 ± 0.48 → 11.10 ± 0.48 µM/mg, ∼48 % increase). SG also attenuated neuroinflammation (IL-6 211.1 ± 10.6 → 165.0 ± 23.6 pg/mL, ∼22 % decrease; TNF-α 179.3 ± 8.7 → 133.7 ± 7.8 pg/mL, ∼25 % decrease; IL-10 12.3 ± 1.0 → 30.2 ± 5.2 pg/mL, ∼146 % increase) and lowered AChE activity (10.61 ± 0.61 → 8.49 ± 0.49 µM/min/mg, ∼20 % decrease). H&E micrographs qualitatively suggested reduced cortical neuronal degeneration.

Conclusions

SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.
背景:阿尔茨海默病(AD)的特征是与胆碱能功能障碍、氧化应激和神经炎症相关的认知能力下降。Saraswata Ghrita (SG)是一种经典的阿育吠陀配方,使用集成的硅-体内工作流程对乙酰胆碱酯酶(AChE)及其相关途径进行了评估。方法:采用GC-MS/MS和HR-LCMS/MS- qtof对SG成分进行分析。优先考虑可渗透bbb的药物样候选药物(SwissADME/BOILED-Egg),并通过对接和分子动力学进行评估。在体内,小鼠接受AlCl₃(4mg/kg, i.p.)。+ d -半乳糖(50mg/kg,每日1次),60天;第31-60天给予SG(3、6、12mL/kg,口服)或多奈哌齐(0.5mg/kg, i.p)。评估行为、生化和组织学终点(n = 6/组)。结果:LIG_91与LIG_212的AChE结合力预测最高(-8.5kcal·mol⁻¹),LIG_91与LIG_212的AChE结合力预测最高(-7.8kcal·mol⁻¹)。AlCl₃+ d -半乳糖认知障碍(MWM d -4 ELT 85.8±5.3s; TSTQ 34.6±2.2s)。SG 12mL/kg提高了MWM性能(ELT 44.1±3.2s,比模型降低~49%;TSTQ 50.1±2.8s,提高~45%),而多奈哌齐的改善更大(ELT 26.7±2.4s,降低~69%;TSTQ 58.1±5.4s,提高~68%)。SG 12mL/kg降低氧化应激(TBARS 12.93±1.58→8.84±0.52nM/mg,降低~32%),提高抗氧化能力(GSH 7.52±0.48→11.10±0.48µM/mg,提高~48%)。SG还能减轻神经炎症(IL-6 211.1±10.6→165.0±23.6pg/mL,降低~22%;TNF-α 179.3±8.7→133.7±7.8pg/mL,降低~25%;IL-10 12.3±1.0→30.2±5.2pg/mL,升高~146%),降低AChE活性(10.61±0.61→8.49±0.49µM/min/mg,降低~20%)。H&E显微镜定性显示皮质神经元变性减少。结论:在该模型中,SG给药与认知改善和胆碱能、氧化和炎症标志物的部分正常化有关。计算结果支持可能的乙酰胆酸参与,但不确定;进一步的定量组织学和标准化配方研究是必要的。
{"title":"Saraswata Ghrita mitigates AlCl₃- and D-galactose–induced cognitive deficits in a murine Alzheimer’s-like model: In silico and in vivo insights","authors":"Robin Badal ,&nbsp;Balveer Kaur ,&nbsp;Harvinder Singh ,&nbsp;Poonam Sharma ,&nbsp;Pramod Yadav ,&nbsp;Arun Mahapatra ,&nbsp;Shivani Ghildiyal ,&nbsp;Ashok Kumar Patel ,&nbsp;Lalan Kumar ,&nbsp;Bhupesh Sharma ,&nbsp;Pradeep Kumar Prajapati ,&nbsp;Tanuja Nesari","doi":"10.1016/j.brainresbull.2026.111742","DOIUrl":"10.1016/j.brainresbull.2026.111742","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is characterized by cognitive decline linked to cholinergic dysfunction, oxidative stress, and neuroinflammation. Saraswata Ghrita (SG), a classical Ayurvedic formulation, was evaluated using an integrated in silico–in vivo workflow focusing on acetylcholinesterase (AChE) and related pathways.</div></div><div><h3>Methods</h3><div>SG constituents were profiled by GC–MS/MS and HR-LCMS/MS-QTOF. BBB-permeable, drug-like candidates were prioritized (SwissADME/BOILED-Egg) and evaluated by docking and molecular dynamics. In vivo, mice received AlCl₃ (4 mg/kg, i.p.) + <span>D</span>-galactose (50 mg/kg, i.p.) for 60 days; SG (3, 6, 12 mL/kg, p.o.) or donepezil (0.5 mg/kg, i.p.) was administered on days 31–60. Behavioral, biochemical, and histological endpoints were assessed (n = 6/group).</div></div><div><h3>Results</h3><div>In silico, LIG_91 showed the top predicted AChE binding affinity (−8.5 kcal·mol⁻¹) and LIG_212 scored −7.8 kcal·mol⁻¹ (supportive evidence). AlCl₃+<span>D</span>-galactose impaired cognition (MWM day-4 ELT 85.8 ± 5.3 s; TSTQ 34.6 ± 2.2 s). SG 12 mL/kg improved MWM performance (ELT 44.1 ± 3.2 s, ∼49 % lower vs model; TSTQ 50.1 ± 2.8 s, ∼45 %higher), while donepezil produced greater improvement (ELT 26.7 ± 2.4 s, ∼69 % lower; TSTQ 58.1 ± 5.4 s, ∼68 %higher). SG 12 mL/kg reduced oxidative stress (TBARS 12.93 ± 1.58 → 8.84 ± 0.52 nM/mg, ∼32 % decrease) and improved antioxidant status (GSH 7.52 ± 0.48 → 11.10 ± 0.48 µM/mg, ∼48 % increase). SG also attenuated neuroinflammation (IL-6 211.1 ± 10.6 → 165.0 ± 23.6 pg/mL, ∼22 % decrease; TNF-α 179.3 ± 8.7 → 133.7 ± 7.8 pg/mL, ∼25 % decrease; IL-10 12.3 ± 1.0 → 30.2 ± 5.2 pg/mL, ∼146 % increase) and lowered AChE activity (10.61 ± 0.61 → 8.49 ± 0.49 µM/min/mg, ∼20 % decrease). H&amp;E micrographs qualitatively suggested reduced cortical neuronal degeneration.</div></div><div><h3>Conclusions</h3><div>SG administration was associated with improved cognition and partial normalization of cholinergic, oxidative, and inflammatory markers in this model. Computational findings support possible AChE engagement but are not definitive; further quantitative histology and standardized-formulation studies are warranted.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111742"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CircHIPK3 regulates TGF-β1/smad3 signaling in communicating hydrocephalus after intraventricular hemorrhage by sponging miR-30a-3p via ACT1 CircHIPK3通过ACT1海绵化miR-30a-3p,调控TGF-β1/smad3信号在脑室内出血后脑积水通讯中的作用
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.brainresbull.2026.111751
Yexin Yuan , Qian Ouyang , Yijian Yang , Junqiang Wang , Kaiyue Wang , Peng Long , Yifeng Chen , Zhikun Liu , Zhiping Zhang , Zhangjie Su , Gelei Xiao
While circRNAs have been demonstrated to play critical roles in various neurological disorders, their functional mechanisms in post-intraventricular hemorrhage (IVH) communicating hydrocephalus remain poorly understood. Here we report a circular RNA, circular RNA homeodomain interacting protein kinase 3 (circHIPK3), significantly upregulated in meningeal tissues of IVH rat models. Knockdown of circHIPK3 markedly attenuated meningeal fibrosis, reduced ventricular dilation, and improved neurological function in IVH rats. Using both IVH rat models and thrombin-induced astrocyte cell lines, we validated the functional role of circHIPK3 in the pathogenesis of IVH-induced communicating hydrocephalus. Mechanistically, circHIPK3 functions as an endogenous sponge of miR-30a-3p to decrease its activity, resulting in upregulation of ACT1(TRAF3IP2) expression, which in turn triggers TGF-β1/Smad3 signaling pathway activation, ultimately driving fibrotic progression after IVH. Collectively, our findings suggest that circHIPK3 and its coupling mechanism are implicated in IVH, providing compelling evidence that circHIPK3 could be a key therapeutic target against post-IVH communicating hydrocephalus.
尽管环状rna已被证明在各种神经系统疾病中发挥关键作用,但它们在脑室内出血(IVH)后脑积水中的功能机制仍知之甚少。在这里,我们报道了一种环状RNA,环状RNA同源结构域相互作用蛋白激酶3 (circHIPK3),在IVH大鼠模型的脑膜组织中显著上调。在IVH大鼠中,敲低circHIPK3可显著减轻脑膜纤维化,减少心室扩张,并改善神经功能。通过IVH大鼠模型和凝血酶诱导的星形胶质细胞系,我们验证了circHIPK3在IVH诱导的交通性脑积水发病机制中的功能作用。机制上,circHIPK3作为miR-30a-3p的内源性海绵,降低其活性,导致ACT1(TRAF3IP2)表达上调,进而触发TGF-β1/Smad3信号通路激活,最终推动IVH后纤维化进展。总的来说,我们的研究结果表明circHIPK3及其偶联机制与IVH有关,提供了令人信服的证据,表明circHIPK3可能是IVH后通讯性脑积水的关键治疗靶点。
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引用次数: 0
Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia 在缺氧时,大脑功能连接在临界氧阈下启动结构重组。
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.brainresbull.2026.111748
Daehun Kang , Koji Uchida , Clifton R. Haider , Norbert G. Campeau , Myung-Ho In , Erin M. Gray , Joshua D. Trzasko , Kirk M. Welker , Matt A. Bernstein , Max R. Trenerry , David R. Holmes III , Michael J. Joyner , Timothy B. Curry , John Huston III , Yunhong Shu
The human brain, one of the most energy-demanding organs, continuously adapts to internal and external challenges. Hypoxia, a reduction in oxygen availability, poses a substantial threat to brain function. Despite its importance, the nature of the brain’s adaptive response to hypoxia remains poorly understood. In this study, we investigated dynamic functional connectivity (FC) under acute hypoxic conditions (FiO2 = 7.7 % and 11.8 %) in healthy adults using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and concurrent advanced physiological monitoring, including partial pressures of end-tidal oxygen (PetO2) and carbon dioxide (PetCO2) and peripheral oxygen saturation (SpO2), and a Go/No-Go cognitive task to assess behavioral performance. Principal component analysis identified a hypoxia-responsive component in dynamic FCs across 400 cerebral parcels. This component captured hypoxia-specific FC changes that coincided with a critical drop in PetO2 (∼53 mmHg), preceding subsequent changes in SpO2, bulk BOLD signals, and behavioral performance. These FC changes were network-specific, with a marked increase primarily centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, hypoxia-responsive connectivity showed limited involvement of visual networks, including connectivity with the DMN. These findings suggest that the brain engages in proactive and structured FC adaptations in anticipation of oxygen decline, rather than in response to it. FC-based metrics offer new insights into the temporal dynamics of brain resilience and may hold translational value for the early detection of vulnerability in neurological or neurodegenerative disorders.
人类的大脑是最需要能量的器官之一,不断适应内部和外部的挑战。缺氧是指氧气供应减少,对大脑功能构成重大威胁。尽管它很重要,但大脑对缺氧的适应性反应的本质仍然知之甚少。在这项研究中,我们利用血氧水平依赖(BOLD)功能磁共振成像(fMRI)和同步先进的生理监测,研究了健康成人在急性缺氧条件下(FiO2 = 7.7%和11.8%)的动态功能连接(FC),包括末期氧(PetO2)和二氧化碳(PetCO2)分压和外周氧饱和度(SpO2),以及Go/No-Go认知任务来评估行为表现。主成分分析确定了400个脑包区动态fc中的缺氧反应成分。该组件捕获缺氧特异性FC变化,与PetO2 (~53mmHg)的临界下降相一致,随后SpO2、大量BOLD信号和行为表现发生变化。这些FC变化是特定于网络的,显著的增加主要集中在默认模式网络(DMN),该网络有选择地与其他高级认知网络同步。相比之下,低氧反应连接显示视觉网络的参与有限,包括与DMN的连接。这些发现表明,大脑在预期氧气减少的情况下进行主动和有组织的FC适应,而不是对氧气减少做出反应。基于fc的指标为大脑恢复力的时间动态提供了新的见解,并可能对神经或神经退行性疾病的早期易感性检测具有转化价值。
{"title":"Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia","authors":"Daehun Kang ,&nbsp;Koji Uchida ,&nbsp;Clifton R. Haider ,&nbsp;Norbert G. Campeau ,&nbsp;Myung-Ho In ,&nbsp;Erin M. Gray ,&nbsp;Joshua D. Trzasko ,&nbsp;Kirk M. Welker ,&nbsp;Matt A. Bernstein ,&nbsp;Max R. Trenerry ,&nbsp;David R. Holmes III ,&nbsp;Michael J. Joyner ,&nbsp;Timothy B. Curry ,&nbsp;John Huston III ,&nbsp;Yunhong Shu","doi":"10.1016/j.brainresbull.2026.111748","DOIUrl":"10.1016/j.brainresbull.2026.111748","url":null,"abstract":"<div><div>The human brain, one of the most energy-demanding organs, continuously adapts to internal and external challenges. Hypoxia, a reduction in oxygen availability, poses a substantial threat to brain function. Despite its importance, the nature of the brain’s adaptive response to hypoxia remains poorly understood. In this study, we investigated dynamic functional connectivity (FC) under acute hypoxic conditions (FiO<sub>2</sub> = 7.7 % and 11.8 %) in healthy adults using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and concurrent advanced physiological monitoring, including partial pressures of end-tidal oxygen (PetO<sub>2</sub>) and carbon dioxide (PetCO<sub>2</sub>) and peripheral oxygen saturation (SpO<sub>2</sub>), and a Go/No-Go cognitive task to assess behavioral performance. Principal component analysis identified a hypoxia-responsive component in dynamic FCs across 400 cerebral parcels. This component captured hypoxia-specific FC changes that coincided with a critical drop in PetO<sub>2</sub> (∼53 mmHg), preceding subsequent changes in SpO<sub>2</sub>, bulk BOLD signals, and behavioral performance. These FC changes were network-specific, with a marked increase primarily centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, hypoxia-responsive connectivity showed limited involvement of visual networks, including connectivity with the DMN. These findings suggest that the brain engages in proactive and structured FC adaptations in anticipation of oxygen decline, rather than in response to it. FC-based metrics offer new insights into the temporal dynamics of brain resilience and may hold translational value for the early detection of vulnerability in neurological or neurodegenerative disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111748"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibiting H3K18 lactylation in microglia aggravates white matter injury after intracerebral hemorrhage in mice 抑制小胶质细胞H3K18乳酸化可加重小鼠脑出血后白质损伤
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.brainresbull.2026.111744
Bing Jiang , Lin Li , Ye Yuan , Zhongyi Zhang , Yuxin Xie , Linhui Zhang , Yihao Tao , Zongyi Xie

Background

White matter injury (WMI) is a key contributor to long-term cognitive deficits following intracerebral hemorrhage (ICH), yet its underlying mechanisms remain incompletely understood.

Aims

This study aims to investigate the role of histone H3K18 lactylation (H3K18la) and microglial function in post-ICH WMI and cognitive impairment.

Methods

Utilizing a collagenase-induced ICH mouse model, we assessed H3K18la expression dynamics (days 3, 7, 14, 21 post-ICH) and the effects of inhibiting lactate dehydrogenase (using Oxamate) or p300/CBP histone acetyltransferase (using A-485) on WMI and cognitive function. Furthermore, we employed PLX5622 (a colony-stimulating factor 1 receptor inhibitor) to deplete microglia (MG), alone or combined with A-485, to examine the role of p300/CBP inhibition in the context of MG absence. WMI was evaluated using myelin basic protein (MBP), neurofilament H (non-phosphorylated; SMI32) immunostaining, and transmission electron microscopy. Oligodendrocyte precursor cell (OPC) accumulation around the hematoma was quantified, and microglial depletion was verified by cell counting. Cognitive function was assessed up to 28 days post-ICH using the Morris Water Maze test.

Results

H3K18la levels were elevated and oligodendrocyte precursor cells (OPCs) increased in the perihematomal region post-ICH. A-485 administration significantly reduced microglial H3K18la, concomitantly suppressed OPC recruitment to the injury site, and exacerbated both WMI and long-term cognitive impairment. In contrast, oxamate administration did not significantly reduce microglial H3K18la or exacerbate cognitive deficits, but it did significantly aggravate WMI. PLX5622-induced MG depletion similarly aggravated WMI and cognitive deficits. However, combined PLX5622 and A-485 treatment did not produce additive worsening compared to MG depletion alone.

Conclusion

These results demonstrated that lactate-derived H3K18 lactylation (H3K18la), orchestrated by p300/CBP-mediated epigenetic reprogramming, serves as a critical endogenous neuroprotective axis of WMI following ICH. Microglia emerge as the cellular executors of this pathway. This lactate-p300/CBP-H3K18la axis thus represents a therapeutically targetable mechanism for enhancing post-hemorrhagic brain repair through microglia-guided myelin regeneration.
脑白质损伤(WMI)是脑出血(ICH)后长期认知缺陷的关键因素,但其潜在机制尚不完全清楚。目的本研究旨在探讨组蛋白H3K18乳酸化(H3K18la)和小胶质细胞功能在脑出血后WMI和认知功能障碍中的作用。方法采用胶原酶诱导的脑出血小鼠模型,观察H3K18la表达动态(脑出血后第3、7、14、21天),以及抑制乳酸脱氢酶(使用草酸酯)或p300/CBP组蛋白乙酰转移酶(使用a -485)对WMI和认知功能的影响。此外,我们使用PLX5622(一种集落刺激因子1受体抑制剂)单独或与a -485联合消耗小胶质细胞(MG),以检查p300/CBP抑制在MG缺失的情况下的作用。采用髓鞘碱性蛋白(MBP)、神经丝H(非磷酸化;SMI32)免疫染色和透射电镜评估WMI。定量血肿周围少突胶质前体细胞(OPC)的积累,并通过细胞计数证实小胶质细胞的耗竭。使用Morris水迷宫测试评估脑出血后28天的认知功能。结果脑出血后血周sh3k18la水平升高,少突胶质前体细胞(OPCs)增多。A-485可显著降低小胶质细胞H3K18la,同时抑制OPC向损伤部位的募集,并加重WMI和长期认知障碍。相比之下,给药并没有显著降低小胶质细胞H3K18la或加重认知缺陷,但确实显著加重了WMI。plx5622诱导的MG消耗同样加重了WMI和认知缺陷。然而,与单独MG消耗相比,PLX5622和A-485联合治疗不会产生累加性恶化。结论通过p300/ cbp介导的表观遗传重编程,乳酸源性H3K18乳酸化(H3K18la)是脑出血后WMI的重要内源性神经保护轴。小胶质细胞作为这一途径的细胞执行者出现。因此,乳酸-p300/CBP-H3K18la轴代表了一种可靶向治疗的机制,可通过小胶质细胞引导的髓磷脂再生来增强出血性脑修复。
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引用次数: 0
Time-dependent alterations in brain metabolites and gut microbiota following whole-brain FLASH versus conventional radiotherapy in mice. 小鼠全脑闪光灯与常规放疗后脑代谢物和肠道微生物群的时间依赖性改变
IF 3.7 3区 医学 Q2 NEUROSCIENCES Pub Date : 2026-02-01 Epub Date: 2026-01-30 DOI: 10.1016/j.brainresbull.2026.111755
Renke He, Yuhan Liu, Wenxuan Li, Shengqiang Xie, Jiayu Liu, Gang Cheng, Jianning Zhang

Purpose: This study compared the time-dependent changes in brain metabolites and gut microbiota at early and late post-irradiation stages in mice receiving conventional radiotherapy (CONV-RT) or ultra-high dose-rate FLASH radiotherapy (FLASH-RT).

Methods: Male C57BL/6 J mice received whole-brain irradiation using CONV-RT (2 Gy/min) or X-ray-based FLASH-RT (200 Gy/s). Brain tissue and gut contents were collected on days 1, 3, 7, and 21 post-irradiation. Targeted LC-MS metabolomics profiled dynamic brain metabolite changes, and 16S rRNA sequencing characterized gut microbiota trajectories. Neuroinflammation and brain injury were assessed by immunofluorescence (microglia/astrocyte markers) and laser speckle cerebral blood flow imaging, while behavioral assays evaluated cognition and anxiety-like behaviors.

Results: Compared with CONV-RT, FLASH-RT was associated with less pronounced hippocampal microglial and astrocytic reactivity, a smaller reduction in cerebral blood flow perfusion, and attenuated radiation-associated cognitive deficits. Metabolomics revealed distinct temporal trajectories: CONV-RT showed sustained late-phase suppression of metabolic programs, whereas FLASH-RT exhibited a coordinated late-stage rebound in pathways related to amino acid/carbohydrate metabolism and synaptic neurotransmission. Mechanistically relevant metabolites linked to antioxidation, energy metabolism, and neural repair were increased under FLASH-RT, consistent with reduced neuroinflammation. Gut microbiota profiling demonstrated that FLASH-RT induced a milder and more transient dysbiosis, with faster restoration toward a Sham-like structure and enrichment of putative beneficial taxa (including Lachnospiraceae, Peptostreptococcaceae, and Dubosiella), while CONV-RT was associated with more persistent Proteobacteria/Enterobacteriaceae-related disruptions and opportunistic signatures.

Conclusion: In summary, we have innovatively explored the changes in brain metabolites and gut microbiota induced by FLASH-RT whole-brain irradiation, providing a theoretical foundation for further investigation into the mechanisms underlying FLASH-RT's effects.

目的:本研究比较了接受常规放疗(convr - rt)或超高剂量率FLASH放疗(FLASH- rt)的小鼠在放疗后早期和晚期脑代谢物和肠道微生物群的时间依赖性变化。方法:雄性C57BL/6J小鼠采用convr - rt (2Gy/min)或基于x射线的FLASH-RT (200Gy/s)全脑照射。于照射后第1、3、7和21天收集脑组织和肠道内容物。靶向LC-MS代谢组学分析了大脑代谢物的动态变化,16S rRNA测序分析了肠道微生物群的变化轨迹。通过免疫荧光(小胶质细胞/星形胶质细胞标记物)和激光斑点脑血流成像评估神经炎症和脑损伤,而行为测试评估认知和焦虑样行为。结果:与convrt相比,FLASH-RT与较不明显的海马小胶质细胞和星形胶质细胞反应性,较小的脑血流灌注减少以及辐射相关的认知缺陷相关。代谢组学揭示了不同的时间轨迹:convr - rt表现出持续的晚期代谢程序抑制,而FLASH-RT在氨基酸/碳水化合物代谢和突触神经传递相关途径中表现出协调的晚期反弹。在FLASH-RT下,与抗氧化、能量代谢和神经修复相关的机制相关代谢物增加,与神经炎症减少一致。肠道菌群分析表明,FLASH-RT诱导了更温和、更短暂的生态失调,更快地恢复到假体样结构,并丰富了假定的有益分类群(包括毛螺杆菌科、胃链球菌科和杜波菌科),而convr - rt与更持久的变形菌门/肠杆菌科相关的破坏和机会性特征有关。综上所述,我们创新性地探索了FLASH-RT全脑照射诱导的脑代谢物和肠道微生物群的变化,为进一步研究FLASH-RT的作用机制提供了理论基础。
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引用次数: 0
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Brain Research Bulletin
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