Brain Research Bulletin最新文献

{"title":"MO-GCN: A multi-omics graph convolutional network for discriminative analysis of schizophrenia","authors":"Haiyuan Wang ,&nbsp;Runlin Peng ,&nbsp;Yuanyuan Huang ,&nbsp;Liqin Liang ,&nbsp;Wei Wang ,&nbsp;Baoyuan Zhu ,&nbsp;Chenyang Gao ,&nbsp;Minxin Guo ,&nbsp;Jing Zhou ,&nbsp;Hehua Li ,&nbsp;Xiaobo Li ,&nbsp;Yuping Ning ,&nbsp;Fengchun Wu ,&nbsp;Kai Wu","doi":"10.1016/j.brainresbull.2025.111199","DOIUrl":"10.1016/j.brainresbull.2025.111199","url":null,"abstract":"<div><div>The methodology of machine learning with multi-omics data has been widely adopted in the discriminative analyses of schizophrenia, but most of these studies ignored the cooperative interactions and topological attributes of multi-omics networks. In this study, we constructed three types of brain graphs (BGs), three types of gut graphs (GGs), and nine types of brain-gut combined graphs (BGCGs) for each individual. We proposed a novel methodology of multi-omics graph convolutional network (MO-GCN) with an attention mechanism to construct a classification model by integrating all BGCGs. We also identified important brain and gut features using the Top<em>k</em> pooling layer and analyzed their correlations with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) scores. The results showed that the novel MO-GCN model using BGCGs outperformed the GCN models using either BGs or GGs. In particular, the accuracy of the best model by 5-fold cross-validation reached 84.0 %. Interpretability analysis revealed that the top 10 important brain features were primarily from the hippocampus, olfactory, fusiform and pallidum, which were involved in the brain systems of memory, learning and emotion. The top 10 important gut features were primarily from <em>Dorea</em>, <em>Ruminococcus</em>, <em>Subdoligranulum</em> and <em>Clostridium</em>, etc. Moreover, the important brain and gut features were significantly correlated with the PANSS and MCCB scores, respectively. In conclusion, the MO-GCN can effectively improve the classification performance and provide a potential gut microbiota-brain perspective for the understanding of schizophrenia.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111199"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of 12/15-lipoxygenase in ischemic stroke","authors":"Xuening Wang ,&nbsp;Qiuji Shao ,&nbsp;Yuan Gao","doi":"10.1016/j.brainresbull.2025.111194","DOIUrl":"10.1016/j.brainresbull.2025.111194","url":null,"abstract":"<div><div>The arachidonic acid metabolic pathway is a classic inflammatory pathway. 12/15-lipoxygenase (LOX), a member of the lipoxygenase family that metabolizes arachidonic acid, has been implicated in the pathogenesis of numerous central nervous system (CNS) diseases. Ischemic stroke is a devastating disease in which the occlusion of cerebral arteries leads to a series of pathophysiological changes in brain tissue, triggering an inflammatory cascade within the brain that results in neuroinflammation. Prior research has shown that 12/15-LOX levels in the brain are elevated following stroke. In this review, we elaborate on the key pathological mechanisms that unfold following ischemic stroke, including neuroinflammation, oxidative stress, neuronal apoptosis, and blood-brain barrier disruption, and present evidence demonstrating that 12/15-LOX inhibition could be used to treat ischemic stroke through various avenues. Furthermore, we list currently available inhibitors of 12/15-LOX and the preclinical or clinical applications, offering novel insights for the early diagnosis, prognosis evaluation, and targeted therapy in neurological diseases.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111194"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological function is restored post-ischemic stroke in zebrafish, with aging exerting a deleterious effect on its pathology","authors":"Takamasa Mizoguchi ,&nbsp;Ayumi Maki ,&nbsp;Yuno Nakase ,&nbsp;Mayu Okita ,&nbsp;Yuina Minami ,&nbsp;Misa Fukunaga ,&nbsp;Motoyuki Itoh","doi":"10.1016/j.brainresbull.2025.111225","DOIUrl":"10.1016/j.brainresbull.2025.111225","url":null,"abstract":"<div><div>Ischemic stroke (IS) is a pathological condition characterized by the cessation of blood flow due to factors such as thrombosis, inflicting severe damage to the cranial nervous system and resulting in numerous disabilities including memory impairments and hemiplegia. Despite the critical nature of this condition, therapeutic options remain limited, with a pressing challenge being the development of treatments aimed at restoring neurological function. In this study, we leveraged zebrafish, renowned for their exceptional regenerative capabilities, to analyze the pathology of IS and the subsequent recovery process. We induced photothrombosis in the telencephalon utilizing rose bengal and conducted a temporal investigation of changes in cerebral vascular function and learning ability. Our findings revealed that blood flow in young zebrafish was restored approximately 7 days post-IS induction (dpi), with brain function recuperating by 14 dpi. Furthermore, we observed an escalation in the expression of the neural stem marker gene at 3dpi, followed by an upregulation of the differentiated neuron marker at 7 and 14dpi. In the aged IS model, symptoms were exacerbated. While cerebral blood flow was restored in 7 days, similar to young zebrafish, the recovery of learning ability was protracted in aged fish. Moreover, an upregulation of the differentiated neuron marker seen in young fish was not observed in the aged model. Collectively, our analysis of the zebrafish IS model and its comparison with existing rodent models may lay the groundwork for novel IS treatment strategies. Furthermore, the zebrafish IS model may prove beneficial for analyzing the impact of aging on the pathology of IS and the recovery process.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111225"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of platelet activation alleviates diabetes-associated cognitive dysfunction via attenuating blood-brain barrier injury","authors":"Fuxing Xu ,&nbsp;Juan Hu ,&nbsp;Xuying Li ,&nbsp;Lan Yang ,&nbsp;Shiqiu Jiang ,&nbsp;Tao Jiang ,&nbsp;Bo Cheng ,&nbsp;Hailiang Du ,&nbsp;Ruiduo Wang ,&nbsp;Yingying Deng ,&nbsp;Wei Gao ,&nbsp;Yansong Li ,&nbsp;Yaomin Zhu","doi":"10.1016/j.brainresbull.2025.111211","DOIUrl":"10.1016/j.brainresbull.2025.111211","url":null,"abstract":"<div><div>Cognitive dysfunction has become the second leading cause of death among the diabetic patients. In pre-diabetic stage, blood-brain barrier (BBB) injury occurs and induced the microvascular complications of diabetes, especially, diabetes-associated cognitive dysfunction (DACD). Endothelial cells are the major component of BBB, on which the increased expression of CD40 could mediate BBB dysfunction in diabetics. Since platelets play an important role in regulating endothelial cell barrier function and over 95 % of the circulating soluble CD40 ligand (sCD40L) is derived from activated platelets, we speculated that the release of CD40L from activated platelets induced by diabetes was the key mechanism that aggravated BBB injury and leaded to DACD. We performed inhibition of platelet activation on diabetic and non-diabetic mice, with or without cilostazol treatment, and then compared cognitive function, platelet activation, BBB structure and permeability. In vitro, mouse brain microvascular endothelial cell line (b.End3) were exposed to CD40L for 24 h at 5.5 mM or 30 mM glucose media after silencing CD40 and HIF1α or not to investigate the effects of CD40 on BBB disruption and the underlying molecular pathways. Inhibition of platelet activation improved cognitive behaviors in diabetic mice, accompanied with reduced BBB permeability, increased tight junction proteins, balanced Aβ transporters, as well as attenuated Aβ deposition and hippocampal neurons damage. <em>In vitro</em>, CD40L increased HIF1α, diminished tight junction proteins and dysregulated Aβ transporters in b.End3 cells, which could be restored by CD40 siRNA and HIF1α siRNA. Hence, inhibition of platelet activation ameliorates DACD via alleviating BBB injury, which involving the regulation of CD40L-CD40-HIF1α signaling pathway. Our study may demonstrate a potential therapeutic target for the treatment of DACD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111211"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth of the prefrontal cortical glioblastoma altered cognitive and emotional behaviors via mediating miRNAs and GABA-A receptor signaling pathways in rats","authors":"Sepide Nateghi ,&nbsp;Ameneh Rezayof ,&nbsp;Fatemeh Kouhkan ,&nbsp;Ladan Delphi ,&nbsp;Yavar Bagheri Davisaraei ,&nbsp;Fatemeh Rostami ,&nbsp;Fatemeh Tirgar ,&nbsp;Houri Sepehri","doi":"10.1016/j.brainresbull.2025.111227","DOIUrl":"10.1016/j.brainresbull.2025.111227","url":null,"abstract":"<div><div>The present study investigated the impact of GABAergic signaling and miRNA expression on glioblastoma multiforme (GBM) growth within the medial prefrontal cortex (mPFC) and its associated cognitive and emotional impairments. The implantation of C6 cells into the mPFC induced GBM in this brain region (referred to as the mPFC-GBM) in male Wistar rats via stereotaxic surgery, as confirmed by Magnetic Resonance Imaging (MRI), and Hematoxylin and Eosin (H&amp;E) staining. Repeated microinjections of muscimol, a potent GABA_A receptor agonist, directly into the mPFC-GBM (1 µg/rat/2.5 μl) following tumor induction decreased tumor volume and weight, resulting in an increased survival rate. Conversely, a higher dose of muscimol (6 µg/rat/2.5 μl) increased tumor size and reduced survival. Behavioral alterations induced by GBM, including anxiety-like responses, exploratory behaviors, locomotor activity, and memory formation, were assessed using anxiety-like behavior task, the hole-board test, and the novel object recognition test. Muscimol treatment dose-dependently affected these behaviors in the animals with the mPFC-GBM, bringing their performance with that of the sham group at the dose of 1 µg/rat/2.5 μl. Changes in specific miRNAs expressions, including miR-208, −290–295, −345, −743 and −802 were associated with the growth of the mPFC-GBM under muscimol treatment. These findings suggest that GBM growth into the mPFC profoundly impacts cognitive and emotional behaviors which can be improved by muscimol treatment. Considering that the expression levels of targeted miRNAs could be influenced by the growth of the mPFC-GBM, both with or without muscimol treatment, these non-coding RNAs might serve as potential biomarkers for GBM.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111227"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential therapeutic role of berberine in treating epilepsy focusing on temporal lobe epilepsy: State of art and ongoing perspective","authors":"Bshra A. Alsfouk ,&nbsp;Hayder M. Al-Kuraishy ,&nbsp;Ali K. Albuhadily ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Ahmed M. Abdelaziz ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Mubarak Alruwaili ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.brainresbull.2025.111189","DOIUrl":"10.1016/j.brainresbull.2025.111189","url":null,"abstract":"<div><div>Epilepsy is a neurological disease characterized by unprovoked recurrent epileptic seizures<strong>.</strong> Temporal lobe epilepsy (TLE) is the commonest type of focal epilepsy in adults that resist to the conventional anti-seizure medications (ASMs). Interestingly, ASMs do not affect the epileptogenesis and progression of disease. Therefore, repurposing of natural products with anti-inflammatory, anti-oxidant and anti-seizure effects such as berberine (BRB) may be logical in treating refractory epilepsy and TLE. However, the molecular mechanism of BRB against the development of epilepsy and progression of epileptic seizure mainly in TLE was not fully elucidated. Therefore, we attempt in this review to discuss the potential underlying molecular mechanism of BRB against the development and progression of epilepsy mainly the TLE.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111189"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of wogonin in the treatment of central nervous system and degenerative diseases","authors":"Qingan Fu ,&nbsp;Qingyun Yu ,&nbsp;Hongdan Luo ,&nbsp;Zhekang Liu ,&nbsp;Xiaowei Ma ,&nbsp;Huijian Wang ,&nbsp;Zhijuan Cheng","doi":"10.1016/j.brainresbull.2025.111202","DOIUrl":"10.1016/j.brainresbull.2025.111202","url":null,"abstract":"<div><div>Wogonin, an O-methylated flavonoid extracted from Scutellaria baicalensis, has demonstrated profound neuroprotective effects in a range of central nervous system (CNS) diseases. This review elucidates the pharmacological mechanisms underlying the protective effects of wogonin in CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, epilepsy, anxiety, neurodegenerative diseases, and CNS infections. Wogonin modulates key signaling pathways, such as the MAPK, NF-κB, and ROS pathways, contributing to its anti-inflammatory, antioxidant, and antiapoptotic properties. In ischemic stroke models, wogonin reduces infarct size and enhances neurological outcomes by mitigating inflammation and oxidative stress. For patients with hemorrhagic stroke and traumatic brain injury, it accelerates hematoma regression, mitigates secondary brain damage, and promotes neurogenesis, making it an entirely new treatment option for patients with limited access to this type of therapy. Its anticonvulsant and anxiolytic effects are mediated through GABA-A receptor modulation. Moreover, wogonin shows promise in treating neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease by promoting autophagy and reducing neuroinflammation. Additionally, it exhibits antiviral properties, offering potential benefits against CNS infections. Despite extensive preclinical evidence, further clinical studies are warranted to confirm its efficacy and safety in humans. This review highlights the great therapeutic potential of wogonin in terms of CNS protection. However, despite the substantial preclinical evidence, further large-scale clinical studies are necessary. Future researchers need to further explore the long-term efficacy and safety of wogonin in clinical trials and translate it for early application in the clinical treatment of true CNS disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111202"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translating time: Challenges, progress, and future directions","authors":"Christine J. Charvet ,&nbsp;Alexandra A. de Sousa ,&nbsp;Tatianna Vassilopoulos","doi":"10.1016/j.brainresbull.2025.111212","DOIUrl":"10.1016/j.brainresbull.2025.111212","url":null,"abstract":"<div><div>Mice are the dominant model system to study human health and disease. Yet, there is a pressing need to use diverse model systems to address long-standing issues in biomedical sciences. Mice do not spontaneously recapitulate many of the diseases we seek to study. Accordingly, the relevance of studying mice to understand human disease is limited. We discuss examples associated with limitations of the mouse model, and how the inclusion of a richer array of model systems can help address long standing issues in biomedical sciences. We also discuss a tool called Translating Time, an online resource (<span><span>www.translatingtime.org</span><svg><path></path></svg></span>) that equates corresponding ages across model systems and humans. The translating time resource can be used to bridge the gap across species and make predictions when data are sparse or unavailable as is the case for human fetal development. Moreover, the Translating Time tool can map findings across species, make inferences about the evolution of shared neuropathologies, and inform the optimal model system for studying human biology in health and in disease. Resources such as these can be utilized to integrate information across diverse model systems to improve the study of human biology in health and disease.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111212"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain mapping, biomarker identification and using machine learning method for diagnosis of anxiety during emotional face in preschool children","authors":"Samira Jafari ,&nbsp;Hamid Sharini ,&nbsp;Aliakbar Foroughi ,&nbsp;Afshin Almasi","doi":"10.1016/j.brainresbull.2025.111205","DOIUrl":"10.1016/j.brainresbull.2025.111205","url":null,"abstract":"<div><h3>Background</h3><div>Due to the importance and the consequences of anxiety, the goals of the current study are brain mapping, biomarker identification and the use of an assessment method for diagnosis of anxiety during emotional face in preschool children.</div></div><div><h3>Method</h3><div>45 preschool children participated in this study. Functional Magnetic Resonance Imaging (fMRI) data were taken in fearful and angry conditions. The functional connectivity (FC) for the limbic system were extracted by ROI-to-ROI method. The fMRI biomarkers (FC) were given to machine learning models as input features to diagnose anxiety in children for angry and fearful conditions.</div></div><div><h3>Result</h3><div>The results of the brain mapping comparisons between anxiety and the non-anxiety showed that there was an increased FC between medial prefrontal cortex (MPFC) and right lateral amygdala (RLA) and a decreased FC between left anterior hippocampus (LAH) and left posterior hippocampus (LPH) in the angry condition. There was an increased FC between the pairs of regions, RLA- right anterior hippocampus (RAH), MPFC-LPH, and RAH-LPH in fearful condition. It is possible to use the FC between LAH- right medial amygdala (RMA) and the FC between left medial amygdala (LMA)-RMA, LMA-RLA, LMA-RAH, and left lateral amygdala (LLA)-RLA instead of IQ in angry and fearful conditions, respectively. Based on metrics such as accuracy, recall, precision, and area under the receiver operating characteristic curve, the Logistic Lasso Regression model outperformed the other model in diagnosing anxiety.</div></div><div><h3>Conclusion</h3><div>With these findings, psychiatrists and psychologists can have a better understanding of the brain connectivity in children.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111205"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of electroacupuncture on vascular remodeling in rats with cerebral ischemia by regulating irisin based on VEGF/Akt/eNOS signaling pathway","authors":"Lu Cao ,&nbsp;Wenchao Ding ,&nbsp;Yashuo Feng ,&nbsp;Chong Guan ,&nbsp;Li Liu ,&nbsp;Hongyu Xie ,&nbsp;Kewei Yu ,&nbsp;Dongyan Xu ,&nbsp;Lijuan Zhao ,&nbsp;Xuan Sha ,&nbsp;Xiaoman Deng ,&nbsp;Santian Wu ,&nbsp;Yangrui Wang ,&nbsp;Yi Wu ,&nbsp;Tingting Zhang ,&nbsp;Nianhong Wang","doi":"10.1016/j.brainresbull.2025.111192","DOIUrl":"10.1016/j.brainresbull.2025.111192","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to explore the cumulative effects and expression patterns of electroacupuncture (EA) on irisin secretion, observe the effects of EA on the recovery of neurobehavioral function and vascular remodeling after cerebral ischemia, and elucidate the mechanism by which EA promotes vascular remodeling by regulating irisin expression.</div></div><div><h3>Methods</h3><div>A rat model of left middle cerebral artery occlusion (MCAO) was prepared, and EA was performed. Tissue distribution and expression of irisin were determined by immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Type III fibronectin domain protein 5-silenced adeno-associated virus (rAAV-shFNDC5) was injected into the lateral ventricle as a control. Neurobehavioral function was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and behavioral experiments, while vascular remodeling was evaluated using laser speckle blood flow imaging, and the expressions of irisin and vascular remodeling-related factors were measured by ELISA and Western blotting.</div></div><div><h3>Results</h3><div>The number of FNDC5-positive neurons, fluorescence intensity, and irisin expression reached their maximum increase after 7 days of EA treatment. In addition, the EA group exhibited a significant reduction in cerebral infarct volume and impairment of neurobehavioral function, an increase in cerebral blood flow and microvascular diameter on the ischemic side, and significantly higher expression levels of FNDC5, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS). However, rAAV-shFNDC5 significantly weakened the therapeutic effects of EA.</div></div><div><h3>Conclusions</h3><div>EA upregulated irisin expression, reaching a peak after 7 days of EA and then stabilizing. EA facilitated vascular remodeling after cerebral ischemia, and this might be associated with the activation of the irisin-mediated VEGF/Akt/eNOS signaling pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"221 ","pages":"Article 111192"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}