Brain Research最新文献

{"title":"Editorial: Emerging practices in therapeutic targeting of neurodegenerative diseases by modulating protein kinases","authors":"Md.Imtaiyaz Hassan , Belgin Sever","doi":"10.1016/j.brainres.2025.149956","DOIUrl":"10.1016/j.brainres.2025.149956","url":null,"abstract":"","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149956"},"PeriodicalIF":2.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases as the biomarkers of Alzheimer's disease: a meta-analysis.","authors":"Kwok Kei Mak, Karin JeeEun Nam, Yi-Fang Chuang, Liang-Kung Chen","doi":"10.1016/j.brainres.2025.149954","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149954","url":null,"abstract":"<p><strong>Introduction: </strong>This study systematically investigated the associations of levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) with clinical-phase Alzheimer's disease (AD) to evaluate their potential as biomarkers.</p><p><strong>Methods: </strong>A systematic search of major English and Asian language databases was conducted from inception to December 2024. Following the screening process using predefined inclusion and exclusion criteria, 12 human studies were selected for review. The sample consisted of 1316 participants (806 with clinical-phase AD patients and 510 controls), including 49.7% males with a mean age of 71.2. The outcomes for comparisons between AD status groups were concentrations of gelatinases (MMP-2 and MMP-9) and stromelysins (MMP-3, MMP-10), TIMPs (TIMP-1 and TIMP-2), as well as the MMP-9/TIMP-1 ratio in body fluids. Pooled standardized mean differences (SMDs) were computed using random-effects models and adjusting for the moderators, comprising demographic factors (population, sex, age) and body fluid type, in the meta-analysis. Forest plots and funnel plots were generated to visualize the results and assess publication biases, respectively.</p><p><strong>Results: </strong>Levels of MMP-3 and MMP-9 were significantly higher in AD patients than in controls with the corresponding pooled SMDs (95 %CI) of 0.69 (0.25 to 1.13) and 0.45 (0.08 to 0.82). The association of MMP-3 level with AD status was moderated by population, sex, and body fluid type, whereas the association of MMP-9 was not. The Egger's tests revealed no statistically significant publication biases (P > 0.05).</p><p><strong>Discussion: </strong>This study provides a summary of the past-decade findings about the levels of MMPs and TIMPs in AD patients and controls. Our findings indicate that elevated MMP-3 and MMP-9 are associated with AD. MMP-9, regardless of body fluid type, could be universally used for screening AD individuals with relevance across various demographic groups.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149954"},"PeriodicalIF":2.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring phantom phenomena following brachial plexus block in intact limbs","authors":"Emily Pettersen ,&nbsp;Giacomo Valle ,&nbsp;Paolo Sassu ,&nbsp;Carina Reinholdt ,&nbsp;Max Ortiz-Catalan","doi":"10.1016/j.brainres.2025.149955","DOIUrl":"10.1016/j.brainres.2025.149955","url":null,"abstract":"<div><h3>Background and objective</h3><div>Phantom limb experiences, including phantom limb sensations (PLS) and phantom limb pain (PLP), are common after limb amputation or deafferentation, with PLP significantly impacting quality of life. However, the mechanisms underlying PLP remain unclear, complicating treatment development. Investigating phantom phenomena has been proposed to gain insights into the mechanisms behind the insurgence of PLS and PLP, potentially informing new therapeutic approaches. However, small, heterogeneous samples and a lack of objective pain metrics often limit research on individuals with limb loss.</div><div>Here, we investigate whether phantom experiences, similar to those reported after amputation, also occur in individuals with intact limbs following a brachial plexus nerve block, excluding the brain from afferent and efferent signals.</div></div><div><h3>Methods</h3><div>To investigate the phenomenon, we conducted a multifaceted phenomenological study involving 14 individuals undergoing elective hand or arm surgery under brachial plexus nerve block. Participants were asked to report on the presence of phantom experiences and describe them in terms of vividness, quality, position, telescoping, movements, and pain. Assessments occurred at four-time points: before surgery, during surgery, after surgery, and at home. These findings were then compared to observations in the amputation population.</div></div><div><h3>Results</h3><div>93 % of the participants reported PLS 20–40 min following brachial plexus anesthesia. The most frequently reported qualities of PLS were tingling, heaviness, and warmth. Commonly reported experiences after limb loss, such as distorted limb position, telescoping, and execution of phantom limb movements, were also reported by the participants after the deafferentation. Notably, participants experiencing distorted limb positions did not find them painful or uncomfortable. PLP was reported by only one participant.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that individuals with temporary sensorimotor deafferentation via brachial plexus nerve block experience many phantom phenomena similar to those reported by individuals with limb loss. This suggests that brachial plexus nerve block is a promising model for studying PLP and a potential test bed for its treatment.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149955"},"PeriodicalIF":2.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Drosophila for studying hypoxia-inducible factor (HIF) in neurodegenerative diseases: Advantages versus limitations","authors":"Zoya Serebrovska ,&nbsp;Lei Xi ,&nbsp;Michael Khetsuriani ,&nbsp;Oleksandra Protsenko ,&nbsp;Nadiia Morozova ,&nbsp;Denis A. Tolstun ,&nbsp;Oksana Maksymchuk","doi":"10.1016/j.brainres.2025.149953","DOIUrl":"10.1016/j.brainres.2025.149953","url":null,"abstract":"<div><div>Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in cellular responses to oxygen deprivation and is increasingly recognized as a key regulator in neurodegenerative diseases. <em>Drosophila melanogaster</em> serves as a powerful genetic model for investigating HIF-1α signaling, particularly through its homolog <em>Sima</em>. This review examines the advantages and limitations of using <em>Drosophila</em> to study HIF-1α in the context of neurodegeneration, with a focus on oxidative stress, autophagy, and mitochondrial dysfunction. We discuss the role of HIF-1α/<em>Sima</em> in modulating neuroprotective pathways, including its interactions with DJ-1 (also known as PARK7 Parkinson disease protein 7), SNCA (Alpha-synuclein), and the mTOR-autophagy axis. Moreover, we highlight the potential of <em>Drosophila</em> in elucidating hypoxia-mediated epigenetic modifications, non-coding RNA regulation, and metabolic adaptations relevant to neurodegenerative diseases. Understanding these mechanisms may provide insights into novel therapeutic approaches for the major neurodegenerative conditions in humans, such as Parkinson’s disease and Alzheimer’s disease.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149953"},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galectin-3 in Alzheimer’s disease: pathological roles, biomarker potential, and therapeutic implications","authors":"A Akash ,&nbsp;Mustak Ahamed ,&nbsp;Pratyush Porel ,&nbsp;Khadga Raj Aran","doi":"10.1016/j.brainres.2025.149949","DOIUrl":"10.1016/j.brainres.2025.149949","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid-beta (Aβ) accumulation, tau pathology, and chronic neuroinflammation, leading to cognitive decline and neurodegeneration. Currently available treatments are liable to provide symptomatic relief; hence, researchers are focused on finding some novel molecular targets for developing targeted therapies, and also some biomarkers for early detection. Emerging evidence suggests that Galectin-3 (Gal-3) serves as a key regulator of microglial activation, exhibiting both neuroprotective and neurotoxic effects, depending on the stage of disease. The overexpression of Gal-3 leads to increased neuroinflammation, oxidative stress, and mitochondrial dysfunction, accelerating disease progression while initially promoting Aβ clearance and suppressing immune response. Moreover, Gal-3 has been associated with tau hyperphosphorylation and aggregation, hence exacerbating synaptic dysfunction and neuronal damage. Elevated levels of Gal-3 in cerebrospinal fluid (CSF) and serum correlate with disease severity, indicating its potential as a biomarker for early diagnosis and disease monitoring. Establishing Gal-3 inhibitors as a potential therapeutic target, several preclinical studies indicate their ability to lower Aβ and tau accumulation by regulating pro-inflammatory signaling and enhancing clearance mechanisms. This approach reduces neuroinflammation by suppressing microglial activation and improves cognitive function by preserving neuronal function and lowering oxidative stress. This review is intended to discuss the intricate role of Gal-3 in AD pathology, such as Aβ aggregation, tau pathology, neuroinflammation, oxidative stress, and microglial activation. Further, it explores the therapeutic strategies that Gal-3 could serve as a novel biomarker for tracing the disease, and reviews potential therapeutic approaches through Gal-3 inhibition for AD management.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149949"},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Ginkgo biloba on spatial memory and oxidative metabolism in healthy young rats","authors":"Elif Azra Arnous,&nbsp;Ayşe Arzu Yiğit","doi":"10.1016/j.brainres.2025.149950","DOIUrl":"10.1016/j.brainres.2025.149950","url":null,"abstract":"<div><div><em>Ginkgo biloba</em> (GB) is a yellow-leaved herb used in treating various diseases and cognitive disorders in China since 2000 years. This study investigates the effects of two different doses of GB, in the form of its standardized extract EGb 761, on liver and kidney functions, hippocampal tissue, and recognition and spatial memory in healthy young rats. Twentyone healthy male Sprague-Dawley rats, aged 8 weeks, were utilized. Rats were equally divided into three groups as control group (C) given tap water, experimental groups (GB100 and GB200) given 100 and 200 mg/kg/day GB. Following a 21 days of oral gavage, recognition memory was evaluated using the novel object recognition (NOR) test, while spatial memory were assessed using the Morris water maze (MWM) test. Animals were euthanized 24 h after the completion of the behavioral tests. Tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels were assessed in hippocampal tissue, while thiol, disulfide, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), urea, and creatinine levels were measured in serum samples. The recognition index (RI) in the NOR test was higher in 100 mg/kg GB group compared to control, whith no differences in the MWM test parameters among the groups (P &gt; 0.05). GB200 reduced hippocampal TNF-α and IL-1β levels, while both GB100 and GB200 increased serum thiol levels. GB200 decreased disulfide levels but raised liver enzymes, suggesting potential liver impairment. These findings suggest that while 200 mg/kg GB exerts antioxidant effects, only 100 mg/kg improves recognition memory, and neither dose affects spatial memory.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149950"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic reconfiguration of task-dependent brain networks underpins superior soccer tactical decision-making performance","authors":"ZhongChen Li ,&nbsp;Zhe Qin ,&nbsp;Yaping Cao ,&nbsp;Minghao Huang ,&nbsp;Jian Lang ,&nbsp;Ju Li","doi":"10.1016/j.brainres.2025.149951","DOIUrl":"10.1016/j.brainres.2025.149951","url":null,"abstract":"<div><div>This study investigates the neural mechanisms underlying superior tactical decision-making in soccer by focusing on the dynamic reconfiguration of task-active brain functional networks. Forty participants, divided into two groups based on soccer expertise, performed a tactical decision-making task while undergoing functional magnetic resonance imaging (fMRI). The professional group comprised athletes with over 10 years of intensive training, while the novice group had minimal experience. Utilizing multilayer network analysis, the study examined global and modular brain network properties, including integration, segregation, and flexibility. The results revealed that professionals demonstrated higher decision accuracy, greater global integration, and reduced network flexibility compared to novices. Modular analysis indicated enhanced integration and decreased flexibility within the cingulo-opercular network among experts. Additionally, soccer experts exhibited increased integration between the cingulo-opercular and sensorimotor networks, as well as between the sensorimotor and cerebellar networks. These findings suggest that soccer expertise is associated with optimized brain network dynamics, supporting efficient cognitive processing and superior decision-making. This research provides valuable insights into how long-term training reshapes brain function, offering a neural basis for expertise in sports.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1866 ","pages":"Article 149951"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA HOXA-AS3 drives glioma progression through miR-542-5p-Mediated regulation of HOXA1 and WNT5A signaling","authors":"Lianxu Cui ,&nbsp;Ruiyu He ,&nbsp;Haomin Li ,&nbsp;Siwei Peng ,&nbsp;Meiru Zhang ,&nbsp;Zhanchuan Ma ,&nbsp;Zaiyu Li","doi":"10.1016/j.brainres.2025.149952","DOIUrl":"10.1016/j.brainres.2025.149952","url":null,"abstract":"<div><h3>Background</h3><div>Gliomas represent a class of central nervous system (CNS) malignancies with significant clinical challenges. Our previous work demonstrated that pristimerin treatment effectively suppresses glioma cell progression through the modulation of miR-542-5p expression. However, the upstream regulatory mechanisms controlling miR-542-5p in glioma remain poorly understood.</div></div><div><h3>Methods</h3><div>Using RNA22 v2 bioinformatics tools, we predicted potential lncRNA-miRNA interactions, followed by TCGA database analysis of HOXA-AS3, HOXA1, and WNT5A expression patterns in glioma specimens. The binding of miR-542-5p to HOXA-AS3 and HOXA1 was confirmed by Dual-luciferase reporter gene assay. Functional validation was performed in U373 and U251 cell lines through genetic manipulation, complemented by <em>in vivo</em> tumor xenograft experiments to assess the pathophysiological role of HOXA-AS3.</div></div><div><h3>Results</h3><div>Clinical data revealed significant upregulation of HOXA-AS3 and HOXA1 in glioma tissues (p &lt; 0.001). Silencing HOXA-AS3 in U373 cells markedly inhibited cellular proliferation (p = 0.0033) and migration capacity (p &lt; 0.001), while enhancing apoptosis rates. These effects were reversible through miR-542-5p overexpression. In vivo studies demonstrated that knockdown of HOXA-AS3 suppressed tumor growth (p &lt; 0.05), concomitant with reduced arginase-1 expression in tumor-associated macrophages (p = 0.0012). Survival analysis established significant correlations between elevated HOXA-AS3 (p &lt; 0.0001), HOXA1 (p &lt; 0.0001), and WNT5A (p = 0.011) expression with poor patient prognosis.</div></div><div><h3>Conclusions</h3><div>Our results showed that <em>HOXA-AS3</em> might promote glioma progression via regulating <em>hsa-miR-542-5p/HOXA1</em> and <em>WNT5A</em>.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149952"},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network meta-analysis of migraine therapies: balancing efficacy and safety","authors":"Rajat Sharma ,&nbsp;Ayush Pandey ,&nbsp;Rachna Agarwal ,&nbsp;Shashank Tripathi","doi":"10.1016/j.brainres.2025.149946","DOIUrl":"10.1016/j.brainres.2025.149946","url":null,"abstract":"<div><h3>Introduction</h3><div>Migraine is a common and debilitating neurological condition, affecting roughly 10 % of the global population and placing a significant burden on public health. It occurs in episodes, often characterized by intense headaches accompanied by sensitivity to light (photophobia), sensitivity to sound (phonophobia), and a range of autonomic and sensory disturbances.</div></div><div><h3>Methods</h3><div>A comprehensive search of three databases was conducted up to April 30, 2023. A frequentist network <em>meta</em>-analysis was utilized to estimate both direct and indirect effects across six outcomes. Interventions were ranked independently for each outcome using the p-score. The choice of <em>meta</em>-analysis model was based on the I² statistic: a random-effects model was applied when I² exceeded 30 %, while a fixed-effect model was used when I² was ≤30 %. All statistical analyses were performed using R version 4.3.2.</div></div><div><h3>Results</h3><div>A total of 80 articles were included in current investigation. For change in mean migraine days (MMD) as direct estimate, by taking placebo as reference treatment, suggested statistically significant result for CGRP (Calcitonin Gene-Related Peptide) receptor antagonist [SMD: −0.38 (−0.61, −0.14)], and CGRP mAbs [SMD: −0.35 (−0.41, −0.31)]. The maximum p-score was obtained by CGRP antagonist (0.71). Similarly, direct estimates were calculated for other outcomes of interest. Additionally, the indirect estimates were calculated taking all treatments under investigations as reference treatment, simultaneously, for each outcome of interest.</div></div><div><h3>Conclusion</h3><div>A network <em>meta</em>-analysis of migraine treatments found Triptans to be highly effective for pain, photophobia, phonophobia, and nausea relief, though with a higher risk of adverse events. CGRP antagonists excelled at reducing monthly migraine days but also had increased side effects.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149946"},"PeriodicalIF":2.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating in silico and experimental approaches to uncover the anti-apoptotic effects of anhydrosafflor yellow B via JNK/Bid pathway in ischemic stroke","authors":"Jie Zhou ,&nbsp;Chenxi Zhou ,&nbsp;Qianqian Chen ,&nbsp;Weifeng Jin ,&nbsp;Li Yu ,&nbsp;Yangyang Zhang","doi":"10.1016/j.brainres.2025.149947","DOIUrl":"10.1016/j.brainres.2025.149947","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Ischemic stroke (IS) is a major cause of death and disability worldwide. Anhydrosafflor yellow B (AHSYB) has shown neuroprotective potential. This study aimed to investigate its therapeutic mechanisms, focusing on the mitochondrial apoptotic JNK/Bid pathway.</div></div><div><h3>Methods</h3><div>Network pharmacology was employed to predict candidate AHSYB-IS targets. The potential roles of these targets in biological processes and signaling pathways were explored using GO/KEGG enrichment analysis. A tMCAO model was established, followed by mRNA sequencing to identify differentially expressed genes (DEGs), with special attention given to genes rescued by AHSYB. Gene set enrichment analysis (GSEA) was performed to explore potential signaling pathways involved in AHSYB’s therapeutic effects. Molecular docking was conducted to evaluate the binding affinity of AHSYB with the apoptotic cascade. Finally, an MCAO/R model experimentally confirmed AHSYB’s influence on the JNK/Bid pathway.</div></div><div><h3>Results</h3><div>A total of 67 candidate targets were identified, with enrichment in pathways such as the MAPK signaling pathway and apoptosis. The PPI network showed that genes such as BCL2, CASP3, and MAPK8 had higher degrees. Further mRNA-seq analysis revealed that the rescued genes in tMCAO mice treated with AHSYB were enriched in biological processes such as the regulation of apoptotic signaling pathway, and KEGG pathways, including the MAPK signaling pathway. Ultimately, based on its role in JNK-mediated mitochondrial apoptosis, the JNK/Bid pathway was selected for further molecular docking and experimental validation. AHSYB showed a significant binding affinity with critical proteins in this pathway, with <em>molecular binding energy &lt; -5 kcal·mol⁻¹</em>. In <em>vivo</em> experiments demonstrated that AHSYB significantly improved neurological function (<em>p &lt; 0.01</em>), reduced cerebral infarct volume (<em>p &lt; 0.01</em>), and reduced the mRNA and protein levels of key genes in the JNK/Bid pathway in both serum and brain tissue (<em>p &lt; 0.01</em> or <em>p &lt; 0.05</em>).</div></div><div><h3>Conclusion</h3><div>AHSYB offers neuroprotection by blocking mitochondrial apoptosis through the inhibition of key targets in the JNK/Bid pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1867 ","pages":"Article 149947"},"PeriodicalIF":2.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}