Brain Research Bulletin最新文献

{"title":"Cerebellar subregional atrophy in relapsing-remitting multiple sclerosis: Stage-dependent dynamics and pharmacological modulation","authors":"Xiaohui Zhang ,&nbsp;Jinzhou Feng ,&nbsp;Zhiwei Zhang ,&nbsp;Bin Yu ,&nbsp;Silin Du ,&nbsp;Kai Zhang ,&nbsp;Xiaoya Chen ,&nbsp;Yongmei Li","doi":"10.1016/j.brainresbull.2025.111679","DOIUrl":"10.1016/j.brainresbull.2025.111679","url":null,"abstract":"<div><h3>Background</h3><div>Cerebellar atrophy is increasingly recognized as an important pathological feature of multiple sclerosis (MS). However, the specific patterns at different stages and their alteration by disease-modifying therapies (DMTs) are not well comprehended.</div></div><div><h3>Objective</h3><div>This study aimed to investigate stage-dependent cerebellar subregional volume changes in relapsing-remitting MS (RRMS) and evaluate the effects of different DMT classes on cerebellar atrophy and clinical outcomes.</div></div><div><h3>Methods</h3><div>A total of 181 patients with RRMS and 99 healthy controls were recruited for this study. Patients were stratified by lesion activity into acute-active, chronic-active, and chronic-inactive subgroups, and by pharmacological mechanism into untreated, sphingosine-1-phosphate (S1P)_T (siponimod, fingolimod, and ozanimod) and not_S1P_DMT (dimethyl fumarate and teriflunomide). Cerebellar subregional volumes were quantified using the deep learning-based tool, CerebNet. Group comparisons were conducted, and interaction effects were examined. The correlations between the cerebellar subregions and cognition were subsequently analyzed.</div></div><div><h3>Results</h3><div>In the lesion-activity subgroups, significant volume loss was detected in several posterior cerebellar lobules, including Crus II, VIIIa/b, VIIb, X, Crus I, and IX (all <em>p</em> &lt; 0.05). The acute-active subgroup exhibited additional atrophy in anterior lobules I–IV and vermis IX compared with the chronic-active subgroup (all <em>p</em> &lt; 0.05). In the treatment subgroups, widespread reductions were observed in the posterior lobules Crus I/II, V, VIIb, VIIIb, IX, and X, with most decreases appearing in the untreated groups (all <em>p</em> &lt; 0.05). Pairwise com<em>p</em>arisons displayed region-specific patterns: left VIIIa volume was reduced in the MS_noDrug and MS_not_S1P_DMT groups but increased in the S1P_DMT group, whereas right lobule V in the S1P_DMT and vermis VI in the MS_not_S1P_DMT were both higher (all <em>p</em> &lt; 0.05). The interaction effects of disease stage and treatment were mainly localized to lobules IX and VIIIb, and the volumes of bilateral IX lobules showed a weak positive correlated with cognitive performance.</div></div><div><h3>Conclusion</h3><div>This study demonstrated stage-specific patterns of cerebellar atrophy in RRMS and the heterogeneous, stage-dependent effects of DMTs on posterior cerebellar subregions. Lobules IX and VIIIb emerged as critical loci linking pharmacological modulation with cognitive outcomes. These findings suggest that these regions may serve as potential imaging biomarkers of therapeutic response and prognosis in MS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111679"},"PeriodicalIF":3.7,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713347","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}

{"title":"Microstructural white matter impairments in chronic fatigue syndrome: Evidence of segmental injury in the cingulum bundle","authors":"Kang Wu ,&nbsp;Ziyao Wu ,&nbsp;Sitong Feng ,&nbsp;Tian Zhou ,&nbsp;Yanzhe Ning ,&nbsp;Kuangshi Li ,&nbsp;Hongxiao Jia","doi":"10.1016/j.brainresbull.2025.111671","DOIUrl":"10.1016/j.brainresbull.2025.111671","url":null,"abstract":"<div><h3>Background</h3><div>Chronic fatigue syndrome (CFS) is a neurological disorder characterized by persistent fatigue. Previous studies have shown structural and functional brain alterations in CFS patients. However, how chronic fatigue affects white matter remains unclear.</div></div><div><h3>Methods</h3><div>We recruited 100 CFS patients and 100 healthy controls (HCs) and collected their diffusion weighted imaging (DWI) data along with fatigue severity scores. Group comparisons were conducted using 87 white matter tract templates derived from 1068 healthy individuals to identify impaired tracts. Fiber bundle quantitative analysis was then applied to localize segmental disruptions. Furthermore, a machine learning model was developed to evaluate the importance of the identified tracts in diagnosing CFS, and treatment efficacy analysis was performed to examine the causal relationship between recovery of fiber bundle structure and improvement in fatigue symptoms.</div></div><div><h3>Results</h3><div>Compared with HCs, CFS patients exhibited reduced fractional anisotropy (FA) in the left cingulum parolfactory tract and the left cingulum frontal-parahippocampal tract. The quantitative analysis indicated that disruptions in these two tracts were localized to the middle-posterior portion of the cingulum bundle. Moreover, FA values of the two tracts yielded 85 % accuracy in distinguishing CFS patients, and causal analysis demonstrated that recovery of these segmentally disrupted tracts was associated with improvements in fatigue symptoms.</div></div><div><h3>Conclusions</h3><div>This large-sample study provides comprehensive insights into microstructural impairments induced by chronic fatigue and highlights the critical role of the cingulum bundle in the pathological mechanisms of CFS, thereby advancing our understanding of CFS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111671"},"PeriodicalIF":3.7,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707447","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}

{"title":"CAF-derived exosomes promote the proliferation and invasion of pituitary adenoma cells via miR-184 transfer","authors":"Qiu Du ,&nbsp;Zhiyong Chen ,&nbsp;Weiyu Zhang ,&nbsp;Mengchao Zhu ,&nbsp;Zhichao Yang ,&nbsp;Yaru Li ,&nbsp;Lei Xu ,&nbsp;Jianmin Zhang ,&nbsp;Aijun Peng ,&nbsp;Qingling Feng","doi":"10.1016/j.brainresbull.2025.111678","DOIUrl":"10.1016/j.brainresbull.2025.111678","url":null,"abstract":"<div><div>Pituitary adenomas (PAs) are common intracranial tumors whose mass effects and endocrine dysfunction pose serious threats to patient health. However, the mechanisms underlying their progression, particularly the role of the tumor microenvironment (TME), remain insufficiently studied. Within this context, cancer-associated fibroblasts (CAFs) have been shown to drive tumor development via extracellular matrix remodeling and extracellular vesicle release, but their specific contributions to PA progression remain unclear. In this study, we observed a correlation between PA invasiveness and fibroblast density in the TME. Functionally, both CAFs and CAF-derived exosomes significantly enhanced the proliferation and invasion of PA cells compared to normal fibroblasts. Small RNA sequencing identified 16 upregulated and 8 downregulated miRNAs in CAF-derived exosomes, with KEGG analysis indicating enrichment in MAPK signaling, regulation of actin cytoskeleton, and lysosome-related pathways. Among these, miR-184 was notably upregulated in both CAF-derived exosomes and PA specimens. We further demonstrated that exosomal miR-184 from CAFs could be transferred into PA cells, promoting their proliferation and invasion, while miR-184 knockdown attenuated the tumor-promoting effects of CAF-derived exosomes. Mechanistically, TLE1 was validated as a direct functional target of miR-184. In summary, our study reveals exosomal miR-184 as a key mediator of CAF-driven PA progression, highlighting its potential as a therapeutic target for PAs.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111678"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695852","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}

{"title":"Sodium acetate and sodium butyrate ameliorate postoperative cognitive dysfunction in aged rats by suppressing inflammation and ferroptosis via inhibition of the cGAS-STING signaling pathway","authors":"Kai-Hui Zeng ,&nbsp;Li-Ping Yu ,&nbsp;Zhen Chen ,&nbsp;Xiang Li","doi":"10.1016/j.brainresbull.2025.111677","DOIUrl":"10.1016/j.brainresbull.2025.111677","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication in elderly patients following surgery. Short-chain fatty acids (SCFAs), including acetate and butyrate, exert anti-inflammatory and antioxidant properties; however, their potential neuroprotective roles in POCD remain largely unexplored. Hence, this study investigated whether sodium acetate (NaA) and sodium butyrate (NaB) ameliorate POCD in aged rats and elucidated the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A POCD model was established in aged male Sprague-Dawley rats by exploratory laparotomy under isoflurane anesthesia. NaA or NaB was administered orally prior to surgery. Cognitive function was assessed using the Morris water maze (MWM), Y-maze, and novel object recognition (NOR) tests. Hippocampal inflammatory responses were assessed by measuring TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. Ferroptosis was evaluated by measuring reactive oxygen species (ROS), malondialdehyde (MDA), Fe²⁺ content, antioxidant activities (SOD, GPx, GSH), and the expression of ferroptosis-related genes (TfR1, DMT1, FTH1, FTL, GPX4, and SLC7A11). Activation of the cGAS-STING signaling pathway was examined via Western blot and ELISA. In addition, hippocampal cGAS was overexpressed to assess its causal role.</div></div><div><h3>Results</h3><div>Both NaA and NaB significantly improved cognitive performance in aged POCD rats, as evidenced by enhanced spatial learning and memory in the MWM, increased spontaneous alternation in the Y-maze test, and a higher recognition index in the NOR test. Mechanistically, NaA and NaB markedly suppressed hippocampal inflammation, as evidenced by decreased TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. NaA and NaB also attenuated ferroptosis, indicated by decreased ROS, MDA, and Fe²⁺ levels, restored SOD, GPx, and GSH activities, upregulated GPX4, SLC7A11, FTH1, and FTL expression, and downregulated TfR1 and DMT1 expression in the hippocampus of aged POCD rats. Furthermore, NaA and NaB inhibited activation of the cGAS-STING signaling pathway in the hippocampus of aged POCD rats. Importantly, hippocampal cGAS overexpression reversed the anti-inflammatory, anti-ferroptotic, and cognitive protective effects of NaA and NaB.</div></div><div><h3>Conclusion</h3><div>NaA and NaB ameliorate POCD in aged rats by mitigating hippocampal inflammation and ferroptosis, potentially via inhibition of the cGAS-STING signaling pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111677"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699625","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}

{"title":"MCU knockdown mitigates post-stroke neuroinflammation through SLC33A1-mediated reduction of NR4A1 acetylation","authors":"Zhou Zhou ,&nbsp;Lijuan Liu ,&nbsp;Yicong Zhou ,&nbsp;Yan Yan ,&nbsp;Binbin Wang ,&nbsp;Xin Lv ,&nbsp;Jin Qin ,&nbsp;Zongyu Liu ,&nbsp;Yongyang Liu ,&nbsp;Zihou Meng ,&nbsp;Long You ,&nbsp;Minghan Zhao ,&nbsp;Xuelin Wang ,&nbsp;Guanhui Pei ,&nbsp;Ge Bai ,&nbsp;Chaoyue Meng ,&nbsp;Xiaoyun Liu","doi":"10.1016/j.brainresbull.2025.111676","DOIUrl":"10.1016/j.brainresbull.2025.111676","url":null,"abstract":"<div><div>Post-stroke neuroinflammation remains a critical contributor to disease progression and recovery. Building on our prior finding that knockdown of the mitochondrial calcium uniporter (MCU) confers protection against ischemic injury, and guided by transcriptomic evidence implicating NR4A1. We investigated the underlying mechanism using a mouse middle cerebral artery occlusion model and a microglial oxygen–glucose deprivation/reoxygenation model, coupled with protein interaction and acetylation assays. MCU knockdown significantly reduced infarct volume, improved neurological scores, and suppressed microglial cytokine expression. Mechanistically, MCU did not directly interact with NR4A1 under our conditions; immunoprecipitation–mass spectrometry identified SLC33A1 as a novel MCU interactor. Reduced MCU levels led to decreased SLC33A1 expression, diminished NR4A1 acetylation, and attenuated inflammatory outputs, whereas elevating global acetylation blunted these effects. Collectively, our findings demonstrate that MCU knockdown mitigates cerebral infarction and suppresses microglial inflammation via SLC33A1-dependent control of NR4A1 acetylation, supporting MCU knockdown as a promising strategy for post-stroke anti-inflammatory intervention.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111676"},"PeriodicalIF":3.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683993","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}

{"title":"The pulvinar nucleus and its role in cognitive functions","authors":"Nelson Cortes,&nbsp;Capucine Mandel,&nbsp;Lamyae Ikan,&nbsp;Christian Casanova","doi":"10.1016/j.brainresbull.2025.111672","DOIUrl":"10.1016/j.brainresbull.2025.111672","url":null,"abstract":"<div><div>The pulvinar is a higher-order thalamic hub with widespread cortico-cortical and cortico-limbic connectivity. Here we synthesize evidence that pulvinar circuits shape perception and cognition via three computations: (i) precision-weighted gain for routing information across visual hierarchies, (ii) priority mapping that supports selection of behaviorally relevant stimuli, and (iii) temporal alignment that facilitates feature binding and multisensory integration. We summarize lesion, inactivation and imaging studies linking these operations to attention, sensory gain, and socio-emotional processing. We then review pulvinar-related alterations across neuropsychiatric conditions (e.g., schizophrenia, autism spectrum disorder, major depressive disorder, anxiety), focusing on convergent patterns of thalamo-cortical reconfiguration rather than disorder-general clinical descriptions. Finally, we integrate these findings with contemporary frameworks (predictive coding; distributed global workspace; constructionist theory of emotions), outlining testable predictions about frequency-specific coupling and state-dependent routing between occipito-temporal, fronto-parietal and limbic networks. This concise account situates the pulvinar as a modulatory hub that can influence both sensory and affective dimensions of cognition, and highlights priorities for causal human and animal work.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111672"},"PeriodicalIF":3.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683996","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}

{"title":"Brain network localization of high-frequency heart rate variability: A meta-analysis and coordinate-based network mapping approach","authors":"Yifan Fang ,&nbsp;Tianyi Li ,&nbsp;Wenwen Liang,&nbsp;Qing Du,&nbsp;Chensheng Pan,&nbsp;Zhou Zhu","doi":"10.1016/j.brainresbull.2025.111673","DOIUrl":"10.1016/j.brainresbull.2025.111673","url":null,"abstract":"<div><div>This study investigated the neural mechanisms behind high-frequency heart rate variability (HF-HRV), a marker of cardiac parasympathetic tone, which is crucial for understanding the interplay between physiological and emotional regulation. Previous neuroimaging studies have yielded inconsistent results, making it challenging to identify the specific brain networks involved in cardiac vagal control. To address this issue, we conducted a systematic search of PubMed, Web of Science, and Scopus for studies linking HF-HRV with brain activation coordinates. An Activation Likelihood Estimation (ALE) meta-analysis was performed to identify convergence in brain activation associated with HF-HRV. We subsequently used coordinate-based network mapping to investigate the functional connectivity of brain regions related to HF-HRV, via a database of resting-state functional connectivity from 1000 healthy volunteers. Despite the high heterogeneity among studies, which prevented the ALE meta-analysis from identifying significant voxels or clusters, coordinate-based network mapping revealed consistent network overlap in the subgenual anterior cingulate cortex (sgACC) and ventromedial prefrontal cortex (vmPFC), both of which were positively correlated with HF-HRV. No significantly correlated areas were detected in the brain networks that were negatively correlated with HF-HRV. These findings suggest that HF-HRV is associated with a distributed network of brain regions, with the sgACC and the vmPFC playing crucial roles in cardiac vagal control. This study introduces an innovative approach to understanding the role of the brain in HF-HRV control and provides a foundation for future research into the neural mechanisms underlying cardiac autonomic regulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111673"},"PeriodicalIF":3.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683995","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}

{"title":"Alterations in dynamic regional homogeneity and functional connectivity in lung cancer patients with bone metastasis pain","authors":"Yu Tang ,&nbsp;Tan Cheng ,&nbsp;Lin Tang,&nbsp;Xiaoyu Zhou,&nbsp;Jing Zhang,&nbsp;Yong Tan,&nbsp;Hong Yu,&nbsp;Jing Yang,&nbsp;Daihong Liu,&nbsp;Jiuquan Zhang","doi":"10.1016/j.brainresbull.2025.111670","DOIUrl":"10.1016/j.brainresbull.2025.111670","url":null,"abstract":"<div><h3>Background</h3><div>Although previous neuroimaging studies have characterized static brain activity in bone metastasis pain (BMP), its dynamic functional properties remain largely unexplored. This study aimed to investigate the dynamic brain activity in BMP patients.</div></div><div><h3>Methods</h3><div>We analyzed dynamic regional homogeneity (dReHo) and dynamic functional connectivity (dFC) in 50 right-handed lung cancer patients with BMP(+), 36 without BMP(−), and 32 healthy controls (HCs). Spearman’s correlation was used to evaluate associations with clinical variables.</div></div><div><h3>Results</h3><div>Compared to BMP(−) patients, BMP(+) patients exhibited increased dReHo variability in the right putamen, fusiform gyrus, left middle occipital gyrus (MOG), and left cerebellar lobule VIII (cerebellum_8_L). Relative to HCs, BMP(+) patients showed increased dReHo in the cerebellum_8_L and decreased dReHo in the left anterior cingulate cortex, right inferior temporal gyrus, and frontal lobe. BMP(−) patients displayed decreased dReHo in the right rolandic operculum and putamen compared to HCs. In BMP(+) patients, dReHo variability in the left MOG was positively correlated with pain intensity, while dReHo variability in the right fusiform gyrus was negatively associated with anxiety. Enhanced dFC was observed between the right fusiform/left MOG and cerebellar subregions in BMP(+) compared to BMP(−) patients.</div></div><div><h3>Conclusions</h3><div>This study demonstrates abnormal dynamic brain activity within visual, affective, and sensorimotor networks in patients with BMP. These findings suggest that dReHo/dFC variability may serve as a neuroimaging biomarker for BMP diagnosis and disease monitoring. Furthermore, they provide new insights into the neurophysiological mechanisms of BMP and identify promising targets for neuromodulation-based therapeutic interventions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111670"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145658693","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}

{"title":"Forced and voluntary exercise exert differential neuroprotective effects in cerebral ischemia-reperfusion injury by inhibiting neutrophil infiltration and blood-brain barrier disruption","authors":"Manyao Zou ,&nbsp;Jie Wang ,&nbsp;Long Yu ,&nbsp;Yuqing Bi ,&nbsp;Guofeng Yan ,&nbsp;Hanqing Ding ,&nbsp;Ying Zhang","doi":"10.1016/j.brainresbull.2025.111668","DOIUrl":"10.1016/j.brainresbull.2025.111668","url":null,"abstract":"<div><div>Ischemic stroke is associated with high disability rates, underscoring the urgent need for effective rehabilitation strategies. While exercise rehabilitation promotes functional recovery, the differential therapeutic effects of distinct exercise modalities and their underlying mechanisms remain incompletely understood. Our previous proteomic study showed that exercise administered after cerebral ischemia-reperfusion (CI/RP) strongly inhibited major neutrophil-driven biological processes in the penumbra region, including neutrophil extracellular traps (NETs) formation and integrin-cell surface interactions. Subsequent experimental results demonstrated that forced exercise (F-Ex) more significantly reduced neutrophil infiltration and NETs formation, attenuated blood-brain barrier（BBB）leakage, and upregulated tight junction proteins (TJPs) compared to voluntary exercise (V-Ex). Furthermore, previous studies have established that matrix metalloproteinases (MMPs) are closely linked to BBB disruption. In our study, matrix metalloproteinase-25 (MMP-25/MT6-MMP), was recognized among the most differentially expressed proteins (DEPs) and its expression was associated with neutrophil infiltration. However, the role of MMP-25 in cerebral ischemia remains understudied. Overall, F-Ex conferred greater neurological improvement in early-stage CI/RP injury compared to V-Ex. These results provide evidence-based insights for selecting optimal exercise interventions in post-stroke rehabilitation, elucidate a novel mechanism underlying F-Ex-mediated protection against ischemic brain injury, and implicate MMP-25 as a potential therapeutic target for ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111668"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676625","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}

{"title":"Abnormal dynamic connectivity patterns in self-limited epilepsy with centrotemporal spikes","authors":"Xu Chen ,&nbsp;Linfeng Song ,&nbsp;Jiaren Zhang ,&nbsp;Xuejin Ma ,&nbsp;Binlin Tian ,&nbsp;Yongzhe Li ,&nbsp;Anjie Zhang ,&nbsp;Xiyao Yang ,&nbsp;Yiyun Zhang ,&nbsp;Tijiang Zhang ,&nbsp;Lin Jiang","doi":"10.1016/j.brainresbull.2025.111669","DOIUrl":"10.1016/j.brainresbull.2025.111669","url":null,"abstract":"<div><h3>Objective</h3><div>To characterize the dynamic functional network connectivity (dFNC) patterns in children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to uncover potential abnormalities in neural regulation and related functional impairments.</div></div><div><h3>Materials and methods</h3><div>Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 61 children with SeLECTS and 69 healthy controls (HCs). Independent component analysis (ICA), the sliding window approach and hidden markov modeling (HMM) were employed to systematically investigate potential differences in dFNC properties between the two groups.</div></div><div><h3>Results</h3><div>The dFNC analysis identified four dynamic states, with State 1 occurring most frequently. State 1 and State 3 represented two polarized connectivity patterns, with State 1 characterized by weak/negative connections and State 3 by widespread strong connections. In both states, children with SeLECTS showed significantly reduced connectivity within the dorsal attention network (DAN) compared with HCs (<em>p</em> &lt; 0.001, FDR-corrected). In the connectivity-balanced State 2, children with SeLECTS showed significantly reduced fractional windows (<em>p</em> = 0.009) and mean dwell time (<em>p</em> = 0.018) compared with HCs, whereas no significant differences were observed in State 4. In addition, temporal variability of functional connectivity between the DAN and visual network (VIS) was significantly reduced in SeLECTS (<em>p</em> &lt; 0.001, FDR-corrected), and this variability was positively correlated with full-scale intelligence quotient (FIQ) (<em>p</em> &lt; 0.05). HMM results from another dynamic perspective further confirmed and echoed the above abnormalities.</div></div><div><h3>Conclusion</h3><div>This study revealed abnormal dynamic connectivity patterns of brain networks in children with SeLECTS from a multidimensional dynamic perspective. These macroscopic abnormalities may reflect an underlying excitation–inhibition imbalance in neural networks and provide new insights into brain functional reorganization and the potential neurobiological mechanisms of SeLECTS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111669"},"PeriodicalIF":3.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676631","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}