Brain Research Bulletin最新文献

{"title":"Shen-Xiong-Tong-Mai granule suppresses nerve cell apoptosis to ameliorate ischemic stroke via activating PI3K/Akt signaling pathway","authors":"Fang Yang ,&nbsp;Yujia Zhong ,&nbsp;Xuhong Yang ,&nbsp;Weihong Li ,&nbsp;Yang Zhang","doi":"10.1016/j.brainresbull.2025.111694","DOIUrl":"10.1016/j.brainresbull.2025.111694","url":null,"abstract":"<div><h3>Background</h3><div>Ischemic stroke (IS) is a common subtype of stroke in China, accounting for 60 %-80 % of all stroke cases. Shen-Xiong-Tong-Mai granule (SXTMG) is one of the commonly used herbal medicine formulas in TCM. The present work aimed to explore the predominant active substances and molecular mechanisms underlying SXTMG against IS.</div></div><div><h3>Methods</h3><div>IS animal model and cell model were constructed using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) methods, respectively. The SXTMG and IS targets were predicted using four databases. UPLC/MS analysis was employed to identify the active compounds of SXTMG. The pathway changes were detected using western blot and immunofluorescence staining.</div></div><div><h3>Results</h3><div>Firstly, SXTMG significantly reduced the ischemic area, brain edema, and nerve function injury of MCAO rats, exhibiting crucial anti-IS effects. Totally 22 active compounds were identified in SXTMG based on HPLC-MS/MS results. After bioinformatics analysis, 89 common targets were identified, which were significantly enriched in pathways including apoptosis pathway and PI3K/Akt signaling. Finally, in vitro experiments indicated that SXTMG treatment significantly inhibited the OGD/R HT22 cell apoptosis and activated the PI3K/Akt signaling in OGD/R HT22 cells.</div></div><div><h3>Conclusion</h3><div>SXTMG possessed promising protective effects against IS through triggering PI3K/Akt signaling to suppress nerve cell apoptosis.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111694"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833277","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":"Hippocampal-amygdala subregional characteristic changes predict heterogeneous post-chemotherapy neuropsychological outcomes","authors":"Jiahui Zheng ,&nbsp;Xiaoyu Zhou ,&nbsp;Jing Yang ,&nbsp;Lin Tang ,&nbsp;Yu Tang ,&nbsp;Jing Zhang ,&nbsp;Yong Tan ,&nbsp;Hong Yu ,&nbsp;Xunrong Luo ,&nbsp;Meng Lin ,&nbsp;Daihong Liu ,&nbsp;Jiuquan Zhang","doi":"10.1016/j.brainresbull.2025.111713","DOIUrl":"10.1016/j.brainresbull.2025.111713","url":null,"abstract":"<div><h3>Background</h3><div>The hippocampus and amygdala are interconnected structures critical for cognition. Existing whole-region analyses show inconsistent findings, while subregional changes and their interactions remain unclear. Therefore, we aim to investigate subregional abnormalities in breast cancer patients undergoing neoadjuvant chemotherapy, focusing on both regional and network-level alterations.</div></div><div><h3>Methods</h3><div>A total of 79 breast cancer (BC) patients and 98 healthy controls (HC) were enrolled in our study. The subregional volumes and network measures in BC patients were analyzed at three time points: baseline (B0), following the first cycle of neoadjuvant chemotherapy (NAC) (B1), and at the completion of therapy (B2). These were then compared with those of the HC group at B0. Partial Least Squares Regression (PLSR) identified subregional predictors of chemotherapy-related cognitive dysfunction.</div></div><div><h3>Results</h3><div>Subregional analysis disclosed significant volume disparities in four hippocampal subregions and one amygdala subregion among BC patients across three time points. Compared to B0, 80 % of these regions exhibited volume increases, and 80 % of these differences were statistically significant during the B1. Network analysis demonstrated significant differences in the nodal measures of the Subregion Interconnected Networks in three hippocampal subregions and one amygdalar subregion across the three time points. Notably, all these subregions are located in the right hemisphere, displaying a lateralized distribution pattern. Eleven PLSR models for multidomain cognitive functions demonstrated predictive validity, identifying key subregions as cognitive impairment biomarkers.</div></div><div><h3>Conclusion</h3><div>Chemotherapy induces distinct hippocampal-amygdalar subregional volumetric changes, which possess predictive significance for chemotherapy-related multidomain cognitive impairment in BC patients.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111713"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892039","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":"Peripheral CD200R signaling: A critical regulator of post-stroke inflammation in aged mice","authors":"Conelius Ngwa,&nbsp;Afzal Misrani,&nbsp;Yan Xu,&nbsp;Jingjing Wang,&nbsp;Rodney Ritzel,&nbsp;Fudong Liu","doi":"10.1016/j.brainresbull.2025.111686","DOIUrl":"10.1016/j.brainresbull.2025.111686","url":null,"abstract":"<div><div>The immune responses to ischemic stroke are subjected to endogenous inhibitory pathways that delimitate the post-stroke inflammation. Among them, the interaction between CD200 and its receptor (CD200R) is increasingly recognized for its role in regulating neuroinflammation across various central nervous system (CNS) disorders. In the present study, we have examined the role of central (brain) vs. peripheral CD200R signaling in acute ischemic stroke using aged bone marrow chimeric (BMC) mice (16–19 months old). These chimeras were generated by transplanting bone marrow from CD200R knockout (KO), green fluorescent protein (GFP), or wild-type (WT) donor mice into irradiated recipient mice, and then subjected to a 45-min transient middle cerebral artery occlusion (MCAO). At three days post-stroke, flow cytometry, ELISA, and immunohistochemistry (IHC) were used to assess immune responses. Infarct volumes and neurobehavioral deficits were also evaluated. We found that T cell infiltration into the brain was significantly greater in KO-to-GFP (central CD200R signaling) compared to GFP-to-KO (peripheral CD200R signaling) mice. KO-to-GFP mice also exhibited significantly higher levels of pro-inflammatory cytokines IL-1β and TNF-α in the ischemic brain than GFP-to-KO chimeras. Correspondingly, KO-to-GFP mice showed significantly larger brain infarct volumes and worse neurobehavior deficits compared to GFP-to-KO chimeras. Together, these findings indicate that the peripheral (not the central) CD200R signaling plays a critical role in controlling post-stroke immune responses and delineating ischemic injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111686"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762302","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":"Polyamine pathway in neurological disorders: Potential therapeutic implications based on current evidences","authors":"Mengqi Yan ,&nbsp;Yingying Tang ,&nbsp;Shuo Zhang ,&nbsp;Li Yu ,&nbsp;Cenglin Xu","doi":"10.1016/j.brainresbull.2025.111711","DOIUrl":"10.1016/j.brainresbull.2025.111711","url":null,"abstract":"<div><div>Polyamines (PAs) with a positive charge and low molecular weight, are a class of general biogenic amines that are involved in many important cellular processes, including maintaining nucleic acid stability, controlling ion channel activity, regulating transcription and translation, modulating cell cycle, influencing kinase activity, protecting oxidative damage, and maintaining membrane structure. Cumulative studies have shown that in various neurological disorders, the normal synthesis and metabolism of the polyamine pathway would be disrupted. And the changed polyamine system is believed to participate in the pathophysiological process of the disease through various mechanisms, these include down-regulating or up-regulating PA, putrescine, spermidine, spermine, the key enzymes in the polyamine catabolic pathway include ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SAT1), and spermine oxidase (SMOX). They also play a role in the disease process by affecting different downstream molecular pathways or mechanisms, resulting in distinct changes under different disease conditions. With such implications of polyamine in the disorder process, targeting the synthesis and metabolism of polyamine system emerges as potential approaches for intervening the neurological disorders. We attempted to explore the potential molecular mechanisms and molecular connections involved in polyamines at first. Then, we describe possible links between polyamines and various neurological disorders, and finally the possible therapeutic implications on targeting the polyamine system for the treatment of various disorders were proposed. This review may provide an up-to-date overview to propose the new perspective about targeting PA for developing potential therapeutic strategies.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111711"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899316","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":"Disease-specific network pattern of perinatal depression revealed by Common Orthogonal Basis Extraction","authors":"Yueheng Peng ,&nbsp;Jihan Wang ,&nbsp;Xianyong Fan ,&nbsp;Yue Yu ,&nbsp;Guolin He ,&nbsp;Dawazhuoma ,&nbsp;Lu Jiang ,&nbsp;Tingting Zhang ,&nbsp;Silangquncuo ,&nbsp;Chanlin Yi ,&nbsp;Dezhong Yao ,&nbsp;Bin Lv ,&nbsp;Peng Xu ,&nbsp;Kaibo Shi","doi":"10.1016/j.brainresbull.2026.111719","DOIUrl":"10.1016/j.brainresbull.2026.111719","url":null,"abstract":"<div><div>The clinical diagnosis of perinatal depression (PD) presents considerable challenge, as it is much harder to identify than non-perinatal depression. Psychologically, common emotional fluctuations during pregnancy are easily confounded with depressive symptoms, leading to missed and incorrect diagnoses. Neurologically, pregnancy-induced alterations in brain activity could obscure neuroimaging features specific to PD. Therefore, this study introduced an innovative approach that combined brain network analysis with Common Orthogonal Basis Extraction (COBE) to identify a <em>PD-Specific Network Pattern</em> from resting-state brain networks, as well as validating its efficacy in diagnosis and assessment. Resting-state electroencephalography (EEG) data were collected from 21 patients with PD and 20 healthy pregnant (HP) individuals, from which functional brain networks were constructed. An optimized COBE method was then employed to extract <em>Exclusive Network Pattern</em> for each group, as well as <em>Common Network Pattern</em> shared by all participants (PD + HP). This process enabled the identification of the PD-Specific Network Pattern that most consistent with neural mechanisms of PD. Based on the PD-Specific Network Pattern, <em>PD-Specific Features</em> were derived and applied to train support vector machine and multiple linear regression models, which respectively performed individual-level classification and assessment. This study effectively addressed the limitation of traditional neuroimaging techniques in the diagnosis of PD, providing a new avenue for objective screening and dynamic monitoring of perinatal depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111719"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920917","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":"2026-01-01","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":"Neural damage and inflammation in myotonic dystrophy type 1: Longitudinal analysis of serum NFL, GFAP, and IL-6","authors":"Joana Garmendia ,&nbsp;Garazi Labayru ,&nbsp;Ainhoa Alberro ,&nbsp;Laura Martins-Almeida ,&nbsp;David Otaegui ,&nbsp;Pablo Iruzubieta ,&nbsp;Adolfo Lopez de Munain ,&nbsp;Andone Sistiaga","doi":"10.1016/j.brainresbull.2025.111688","DOIUrl":"10.1016/j.brainresbull.2025.111688","url":null,"abstract":"<div><h3>Introduction</h3><div>Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disease affecting the central nervous system (CNS). Blood-based biomarkers such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) offer potential as non-invasive indicators of CNS dysfunction and/or inflammation. However, their longitudinal dynamics and clinical relevance in DM1 remain unclear. Additionally, sex-related differences in these biomarkers are poorly understood. This study aimed to investigate NFL, GFAP, and IL-6 serum levels in patients with DM1, examine sex-differences, track changes over four years, and explore associations with genetic, muscular, cognitive, and neuroimaging outcomes.</div></div><div><h3>Method</h3><div>Retrospective data from 70 DM1 patients and 54 healthy controls (HC) were analyzed. Longitudinal data were available for 68 participants (39 DM1, 29 HC). Biomarkers were measured using the ELLA immunoassay. DM1 patients had data on genetic, muscular, cognitive and structural brain outcomes. Analyses were adjusted for age.</div></div><div><h3>Results</h3><div>NFL and IL-6 levels were significantly higher in DM1 patients compared to HC, while GFAP levels did not differ. Male DM1 patients exhibited higher NFL and IL-6 levels compared to females. No significant longitudinal changes were observed over a four-year period. NFL and IL-6 levels correlated with larger genetic expansions and poorer cognitive performance.</div></div><div><h3>Discussion</h3><div>NFL and IL-6 may reflect neural damage and systemic inflammation in DM1 and could serve as biomarkers of cognitive dysfunction. However, their limited longitudinal sensitivity suggests longer follow-up is needed to evaluate their utility for disease monitoring.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111688"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773664","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":"AD16 as a novel therapeutic agent: Mechanisms and efficacy in chronic inflammatory pain management","authors":"Zhi-Ping Hu ,&nbsp;Hai-Juan Ma ,&nbsp;Hui Liu ,&nbsp;Zhi-Xian He ,&nbsp;Dan-Dan Jia ,&nbsp;Ya-Lan Sun ,&nbsp;Zhi-Hua Huang ,&nbsp;Zhi-dong Yuan ,&nbsp;Tao Chen ,&nbsp;Cheng Huang","doi":"10.1016/j.brainresbull.2025.111707","DOIUrl":"10.1016/j.brainresbull.2025.111707","url":null,"abstract":"<div><div>Chronic inflammatory pain is a complex condition marked by enduring pain due to inflammation and central sensitization. Present therapeutic strategies primarily rely on non-steroidal anti-inflammatory drugs (NSAIDs) or opioid-based treatments, which frequently entail considerable adverse effects and demonstrate limited efficacy in managing chronic pain. Therefore, there is a pressing need to identify novel therapeutic strategies that can effectively target and modulate the underlying mechanisms of chronic inflammatory pain. Here, we examined an innovation compound named AD16 in mitigating chronic inflammatory pain and investigated its molecular mechanisms. The findings revealed that AD16 significantly attenuated pain-related behaviors in rat models of chronic inflammatory pain induced by complete Freund's adjuvant (CFA), specifically reducing foot swelling and mechanical allodynia. AD16 was found to be associated with the activation of GABA_B receptors and alterations in the expression ratios of GluN2A/GluN2B subunits, suggesting a potential impact on synaptic plasticity. Furthermore, AD16 was correlated with a reduction in systemic inflammatory markers, as demonstrated by decreased levels of IL-1β and increased levels of IL-10 known to play roles in the modulation of central sensitization in inflammatory pain. These findings suggest that AD16 may counteract CFA-induced central sensitization by restoring two critical pathways: (1) the balance between neuronal excitation and inhibition, and (2) the equilibrium between pro-inflammatory and anti-inflammatory immune responses within the spinal cord. Consequently, AD16 represents a promising therapeutic candidate for chronic inflammatory pain.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111707"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848865","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":"2026-01-01","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}

{"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":"2026-01-01","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}