Brain Research Bulletin最新文献

{"title":"Linking VR performance to cognitive ability: The significance of ACC-PCL connectivity in aging populations","authors":"Zhen Gu ,&nbsp;Jing Cao ,&nbsp;Zhiqiang Wu ,&nbsp;Ling Yue","doi":"10.1016/j.brainresbull.2025.111681","DOIUrl":"10.1016/j.brainresbull.2025.111681","url":null,"abstract":"<div><h3>Background</h3><div>Neuropsychological tests provide standardized cognitive assessment but have limited ecological validity. Virtual reality (VR) creates immersive environments, better reflecting real-world cognitive performance. Although impaired VR performance correlates with early cognitive decline, its neural mechanisms remain unclear in non-demented elders. This study investigates fMRI biomarkers linked to VR performance to identify neural predictors of cognitive decline.</div></div><div><h3>Methods</h3><div>24 non-demented older adults, including cognitively normal (CN) and mild cognitive impairment (MCI), completed baseline resting-state fMRI and immersive VR tasks combining physical and cognitive demands (dog walking, mountain climbing, drone protection). VR performance score (VRS) was quantified via entropy weight method. We analyzed relationships between VRS, neuropsychological scores, and resting-state functional connectivity (FC).</div></div><div><h3>Results</h3><div>VRS significantly correlated with MoCA visuospatial/executive scores (p = 0.015). Whole-brain FC analysis revealed a strong association between VRS and FC between the left anterior cingulate cortex (ACC) and left paracentral lobule (PCL) in the overall sample (adjusted p = 1.94 × 10⁻⁶), present in CN but absent in MCI. Stepwise regression confirmed this FC as the significant VRS predictor in CN (R² = 0.599, p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Immersive VR performance reflects visuospatial/executive function and is predicted by left ACC-PCL connectivity, serving as a neuroimaging biomarker for real-world cognition that complements traditional assessments. Practically, this biomarker requires validation in larger longitudinal cohorts.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111681"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734692","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":"Reversal of auditory cortical hyperexcitability and restoration of synaptic plasticity balance by GluN1-mediated photobiomodulation in noise-induced tinnitus","authors":"Zhixin Zhang ,&nbsp;Xinmiao Xue ,&nbsp;Dongdong He ,&nbsp;Peng Liu ,&nbsp;Chi Zhang ,&nbsp;Yvke Jiang ,&nbsp;Shuhan Lv ,&nbsp;Li Wang ,&nbsp;Hanwen Zhou ,&nbsp;Weidong Shen ,&nbsp;Shiming Yang ,&nbsp;Fangyuan Wang","doi":"10.1016/j.brainresbull.2025.111685","DOIUrl":"10.1016/j.brainresbull.2025.111685","url":null,"abstract":"<div><div>Glutamate receptors regulate neuronal excitability and drive synaptic plasticity in the auditory cortex (AC), with aberrant activation or dysfunction contributing to tinnitus pathogenesis. Photobiomodulation (PBM) exerts sustained modulatory effects on neural activity and behavioral responses across species, including humans. However, its therapeutic potential and mechanisms in noise-induced tinnitus remain unexplored. Here, we developed a noninvasive low-irradiance PBM device to target the AC of animal models, investigating near-infrared light mechanisms for reversing cortical hyperexcitability and restoring synaptic plasticity. In noise-exposed tinnitus models without significant neuronal loss, we observed abnormally elevated GluN1 activation and increased synaptic structural complexity compared to non-tinnitus or sham-exposed controls. Tinnitus models were subjected to PBM interventions with varying parameters (irradiance power: 20/40/80 mW/cm²; exposure duration: 300/600 s). Therapeutic efficacy was validated through auditory brainstem response (ABR), gap-prepulse inhibition of acoustic startle (GPIAS), and prepulse inhibition (PPI) behavioral assays. Fluorescence microscopy of brain sections quantified c-Fos/GluN1 co-localization to image activated NMDARs, while Nissl staining assessed PBM safety across parameters. Phosphoproteomic profiling explored mechanistic pathways, with neuronal morphological changes visualized via Golgi staining and transmission electron microscopy. To confirm GluN1’s pivotal role in auditory cognition, we engineered transgenic mice with GluN1 overexpression or knockdown. GluN1-overexpressing mice exhibited tinnitus-like behaviors at specific frequencies, whereas GluN1-deficient tinnitus models showed aberrant behaviors due to impaired auditory cognition. Our findings delineate noise-induced tinnitus mechanisms and PBM-mediated regulation of neuronal excitability and structural plasticity, establishing an irradiance-duration optimization framework for clinical translation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111685"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773670","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":"Cycloastragenol protected hippocampal CA1 neurons by regulating redox homeostasis and alleviated cognitive impairment following cerebral ischemia-reperfusion","authors":"Su Gao ,&nbsp;Shihui Zhu ,&nbsp;Tianyi Qu ,&nbsp;Jiahui Zou ,&nbsp;Lida Yin ,&nbsp;Xuesong Wang ,&nbsp;Xiaokun Yin ,&nbsp;Lin Tong ,&nbsp;Wei Li","doi":"10.1016/j.brainresbull.2025.111689","DOIUrl":"10.1016/j.brainresbull.2025.111689","url":null,"abstract":"<div><h3>Objective</h3><div>This study investigated the neuroprotective effects and mechanisms of cycloastragenol (CAG) on oxidative stress and neurological function in cerebral ischemia-reperfusion injury (CIRI) and oxygen-glucose deprivation/reoxygenation (OGD/R) models.</div></div><div><h3>Methods</h3><div><em>In vivo</em>, rats were given oral CAG daily for 28 days before CIRI induction. Cerebral infarction and hippocampal injury were assessed using TTC, Nissl, and HE staining. Neurological scores, morris water maze, grip strength tests, and brain water content were used to evaluate functional outcomes. Oxidative stress was determined by biochemical assays, DHE staining, and transmission electron microscopy, while Western blotting was performed to measure neuroprotective proteins. <em>In vitro</em>, primary neurons were treated with CAG and subjected to OGD/R. Cell viability was tested by CCK-8 assay, apoptosis and mitochondrial membrane potential were analyzed by flow cytometry, ROS levels were quantified, and MDA, SOD, and GSH were measured biochemically. Western blot further evaluated BDNF and NeuN expression to confirm <em>in vivo</em> findings.</div></div><div><h3>Results</h3><div><em>In vivo</em>, CAG reduced infarct volume and edema, improved neurological deficits, preserved the structural integrity of neurons in the hippocampal CA1 region. CAG also promoted motor function recovery, markedly reduced MDA levels, increased SOD and GSH activity, and upregulated BDNF and NeuN expression. <em>In vitro</em>, CAG enhanced cell viability in the OGD/R model, reduced apoptosis, restored mitochondrial membrane potential, and significantly suppressed oxidative stress induced by ischemia-reperfusion.</div></div><div><h3>Conclusion</h3><div>CAG effectively alleviated injury caused by cerebral and cellular ischemia-reperfusion by maintaining redox homeostasis, inhibiting oxidative stress, and promoting the expression of neuroprotective proteins, demonstrating promising neuroprotective potential.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111689"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773689","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":"Assessment of changes in late positive potential during emotion regulation: Evidence from a three-level meta-analysis","authors":"Xuejing Zou,&nbsp;Han Xiao,&nbsp;Siyu Di,&nbsp;Haiying Qu","doi":"10.1016/j.brainresbull.2025.111700","DOIUrl":"10.1016/j.brainresbull.2025.111700","url":null,"abstract":"<div><h3>Objective</h3><div>A growing body of research has employed event-related potential (ERP) techniques to investigate emotion regulation. However, studies utilizing consistent indicators have yielded divergent and at times contradictory findings. The primary objectives of this study are to systematically evaluate whether significant changes occur in the amplitude of the late positive potential (LPP), a key ERP component, during emotion regulation, and to further assess the temporal dynamics of LPP modulation across different processing stages.</div></div><div><h3>Methods</h3><div>A total of three databases—PubMed, Web of Science, and PsycINFO—were searched for electroencephalography studies related to emotion regulation published between the year 2000 and March 1, 2025, resulting in the inclusion of 48 studies with 150 effect sizes. This meta-analysis utilized CMA3.0 and R4.5 software. When a study reported multiple effect sizes, a three-level meta-analysis was conducted, and publication bias was assessed using funnel plots, the Egger test at the two- and three-levels.</div></div><div><h3>Results</h3><div>The results indicated significant total effect sizes in the central-parietal region across the full, early, and late time windows, while total effect sizes in other brain regions and time windows did not reach statistical significance.</div></div><div><h3>Conclusions</h3><div>The LPP in the central parietal serves as a reliable electrophysiological indicator of emotion regulation (especially cognitive reappraisal), and differences induced by this emotion regulation are more pronounced in early and late time windows.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111700"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809845","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":"Diagnosis of cognitive impairment in chronic kidney disease: A radiomics and machine learning approach with quantitative susceptibility mapping","authors":"Yi-Fan Guo ,&nbsp;Yuan-zhe Li ,&nbsp;Yu Qi ,&nbsp;Xu Liu ,&nbsp;Li-jun Song ,&nbsp;Wen-bo Yang ,&nbsp;Min-gan Li ,&nbsp;Xiao-yan Bai ,&nbsp;Mao-sheng Xu ,&nbsp;Meng-yuan Shen ,&nbsp;Si-qing Cai ,&nbsp;Yi Wang ,&nbsp;Zheng-han Yang ,&nbsp;Zhen-chang Wang ,&nbsp;Hao Wang","doi":"10.1016/j.brainresbull.2025.111714","DOIUrl":"10.1016/j.brainresbull.2025.111714","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) alters magnetic susceptibility within the basal ganglia, contributing to cognitive impairment (CI). This study aims to develop a radiomics-based model using quantitative susceptibility mapping (QSM) and machine learning for diagnosing CKD-related CI.</div></div><div><h3>Method</h3><div>A total of 161 CKD patients were prospectively recruited, with 113 in the training set and 48 in the test set. Radiomic features were extracted from basal ganglia nuclei on QSM images. After preprocessing and feature selection, multiple machine learning algorithms were evaluated. The final radiomics model was selected based on decision curve analysis (DCA) in the test cohort. A combined model was built by integrating clinical characteristics with the radiomics model using multivariable logistic regression. Model performance was assessed using receiver operating characteristic (ROC) analysis and DCA.</div></div><div><h3>Results</h3><div>DCA identified the putamen based support vector machine (SVM) radiomics model as the optimal model. It achieved AUCs of 0.929 (95 % CI 0.870–0.972) in the training set and 0.891 (95 % CI 0.786–0.972) in the test set. The combined model showed further improvement, yielding AUCs of 0.964 (95 % CI 0.928–0.989) and 0.933 (95 % CI 0.856–0.987). DCA indicated the highest net benefit for the combined model.</div></div><div><h3>Conclusion</h3><div>QSM based radiomics of the putamen, especially when combined with clinical characteristics, may serve as a promising noninvasive approach for identifying CKD related CI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111714"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905663","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":"Long non-coding RNA THAP7-AS1 interacts with EIF3A and enhances ITPR1 to enhance endoplasmic reticulum stress and endothelial cell pyroptosis in ischemic stroke","authors":"Yini Pan ,&nbsp;Hui Chen ,&nbsp;Jianhua Xu,&nbsp;Li Zhao,&nbsp;Meifen Yao","doi":"10.1016/j.brainresbull.2025.111706","DOIUrl":"10.1016/j.brainresbull.2025.111706","url":null,"abstract":"<div><div>THAP7-AS1 is a newly discovered long non-coding RNA (lncRNA) whose biological roles in human physiological and pathological processes remain elusive. This study explores the functional impacts of THAP7-AS1 and its interacting molecular cascades in human umbilical vein endothelial cell damage in the context of ischemic stroke. We observed that THAP7-AS1 interacted with EIF3A in human umbilical vein endothelial cells through a combination of RNA-IP, pull-down assays, and immunofluorescence staining assays. Knockdown of either THAP7-AS1 or EIF3A led to a significant reduction in ITPR1 expression, a key regulator of Ca^2 + signaling and pyroptosis. In ischemic stroke models induced by oxygen-glucose deprivation (OGD), THAP7-AS1 was upregulated alongside EIF3A and ITPR1, promoting endothelial cell pyroptosis and endoplasmic reticulum (ER) stress. Knockdown of THAP7-AS1 or EIF3A alleviated OGD-induced pyroptosis and ER stress, while overexpression of ITPR1 exacerbated these conditions. <em>In vivo</em>, inhibition of ITPR1 with Xestospongin C reduces brain infarction and pyroptosis markers in stroke mice. These results suggest that the THAP7-AS1/EIF3A/ITPR1 axis plays a crucial role in ischemic stroke, contributing to endothelial cell dysfunction through pyroptosis and ER stress. Targeting this pathway may offer therapeutic potential for stroke-related endothelial injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111706"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846648","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":"2026-01-01","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":"Understanding the Charles Bonnet syndrome: An updated review","authors":"Sophia E.G. Christoph ,&nbsp;Karl T. Boden ,&nbsp;Berthold Seitz ,&nbsp;Peter Szurman ,&nbsp;André Schulz","doi":"10.1016/j.brainresbull.2025.111683","DOIUrl":"10.1016/j.brainresbull.2025.111683","url":null,"abstract":"<div><div>Charles Bonnet Syndrome (CBS) is a complex and underrecognized condition characterized by visual hallucinations in individuals with visual impairment but preserved cognitive function. This review examines the evolving definitions, epidemiology, risk factors, and pathophysiological models of CBS. Drawing from a broad range of studies, the review identifies key diagnostic inconsistencies and highlights the syndrome’s multifactorial origins, including sensory deprivation and cortical processing imbalances. Epidemiological data suggest CBS affects up to 10 % of visually impaired individuals, though prevalence estimates vary widely due to definitional discrepancies. Risk factors include low visual acuity, female sex, social isolation, and possibly certain medications, though evidence remains inconclusive. Pathophysiological theories such as deafferentation, predictive coding, and the perception-attention deficit model underscore the interplay between bottom-up and top-down mechanisms in hallucination formation. The review also explores differential diagnoses and discusses therapeutic approaches, including vision restoration, pharmacological agents, and psychoeducation. While no standardized treatment exists, early recognition and patient reassurance can significantly improve outcomes. The review calls for clearer diagnostic criteria, further research into neurobiological mechanisms, and longitudinal studies to better understand the prognosis and potential links between CBS and cognitive decline.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111683"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755137","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":"miR-219 ameliorates myelin impairment and cognitive function deficits in the early stage of MCAO/R rats","authors":"Wenxiu Li ,&nbsp;Jianhua Jiang ,&nbsp;Yizhen Weng ,&nbsp;Lulu Zhang ,&nbsp;Quanquan Zhang ,&nbsp;Xinyi He ,&nbsp;Xiang Li, Sr ,&nbsp;Xiang Tang","doi":"10.1016/j.brainresbull.2025.111692","DOIUrl":"10.1016/j.brainresbull.2025.111692","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs). However, its role in myelin damage and cognitive dysfunction during acute cerebral ischemia is not well understood. In this study, we used the MCAO/R rat model to investigate the mechanistic involvement of miR-219. Our results show that miR-219 alleviates cognitive dysfunction induced by MCAO/R. The agonist group showed a reduced time to locate the platform in the water maze, while the antagonist group showed an increased time compared to the solvent control. Additionally, miR-219 reduced myelin damage, as demonstrated by Luxol Fast Blue (LFB) staining, which indicated substantial hippocampal demyelination repair in the agonist group, whereas the antagonist group exhibited aggravated demyelination. Electron microscopy revealed enhanced myelin sheath regeneration and increased thickness in the agonist group, while the antagonist group displayed fewer and thinner myelin sheaths. Furthermore, miR-219 regulated OPC maturation, with more CNPase-positive cells in the agonist group and fewer in the antagonist group than the solvent control. In NG2 staining, the agonist group had fewer positive cells, while the antagonist group had more. miR-219 also decreased Lingo-1 expression, leading to reduced levels of AKT, RhoA, and mTOR in the downstream signaling pathway. These findings suggest that activating the miR-219–Lingo-1 signaling pathway during ischemia-reperfusion could offer a potential therapeutic approach for improving myelin damage and alleviating cognitive dysfunction in cerebral ischemia.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111692"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780419","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":"A critical appraisal of drug transport across the blood-brain barrier: Evaluation using new-age microfluidic technique","authors":"Kiran Marathe ,&nbsp;Dhruv Sanjay Gupta ,&nbsp;Kalyani Barve ,&nbsp;Dhananjay Bodas","doi":"10.1016/j.brainresbull.2025.111662","DOIUrl":"10.1016/j.brainresbull.2025.111662","url":null,"abstract":"<div><div>Research over the past few decades has focused on elucidating the role of the blood-brain barrier (BBB) in neuroprotection, regulation of the brain microenvironment, and mediation of the selective permeability of substances, including drug molecules. This has highlighted its significance in preclinical research, particularly in the screening of novel chemical entities with neuromodulatory properties. The BBB is not a static barrier but a dynamic, multicellular interface known as the neurovascular unit (NVU), which actively regulates brain homeostasis. A persistent challenge in neurotherapeutics is the translatability crisis, where promising results from traditional preclinical models fail to materialize in human trials. Current <em>in vivo</em> models, such as those using rodents and zebrafish, replicate the complexity of the human BBB and demonstrate satisfactory reproducibility, but are limited by their cost, time-consuming nature, and critical issues of interspecies translatability, particularly in the expression and function of key drug transporters. This has driven the development of <em>in vitro</em> models. In recent years, organ-on-a-chip technologies, which utilize the principles of microfluidics, have emerged at the forefront. These models are robust, cost-effective, and enable high-throughput screening of experimental results. By incorporating human-derived cells, physiological shear stress, and 3D architecture, these platforms are evolving from simple permeability-screening tools into sophisticated \"pathophysiology-in-a-dish\" systems. They combine the advantages of both <em>in vivo</em> and <em>in vitro</em> systems and offer promising scalability for modeling neurodegenerative diseases, neuroinflammation, and cancer, thereby enabling more predictive screening of therapeutic candidates. This review aims to provide a perspective on the current understanding of the BBB and its associated transport mechanisms, followed by a discussion of various contemporary models with the potential to transform the drug discovery landscape. The application of microfluidics in designing these models, along with noteworthy case studies in disease modeling, is explored. Finally, a brief overview of current challenges in the field, including the need for standardization, and exciting future directions spurred by regulatory shifts toward non-animal alternative methods is presented.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111662"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676599","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}