Brain Research Bulletin最新文献

{"title":"Mechanism of mild hypothermia induced cold shock protein protecting neural stem cells","authors":"Yuanhui Sun ,&nbsp;Jingwen Xue ,&nbsp;Liangliang Zhang ,&nbsp;Zhichao Zhang ,&nbsp;Sha Sha ,&nbsp;Qi Sun ,&nbsp;Lan Gao ,&nbsp;Hao Li ,&nbsp;Qindong Shi","doi":"10.1016/j.brainresbull.2025.111555","DOIUrl":"10.1016/j.brainresbull.2025.111555","url":null,"abstract":"<div><div>Cardiac arrest (CA) is a leading cause of death in humans. Our previous research confirmed that after CA/cardiopulmonary resuscitation, mild therapeutic hypothermia (MH) promotes neurogenesis in the brain and earlier expression of RNA-binding motif protein 3 (RBM3) in the cerebral cortex and hippocampus of rats. However, the mechanism underlying RBM3 regulating MH-induced neurogenesis remains unclear. This study simulated I/R injury after CA by oxygen-glucose deprivation/reperfusion (OGD/R) of mouse NSCs to determine whether RBM3 mediates the neuroprotective effects of MH in neural stem cells (NSCs) after ischemia-reperfusion (I/R) injury and whether this mechanism involves the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The experimental results showed that the number of newborn NSCs increased significantly in the hypothermic group on days 3 and 5 after OGD/R injury compared with the normothermic group, and the apoptosis of NSCs decreased significantly, we also found that the proportion of NSCs differentiated into neuroglial cells decreased, while the proportion of NSCs differentiated into neurons increased. In NSCs, MH increased the expression of RBM3 after OGD/R injury and activated the PI3K/AKT signaling pathway. By inhibiting this pathway, the effects of MH on promoting NSCs’ proliferation and differentiation and inhibiting their apoptosis were eliminated.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111555"},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102479","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":"Wake-promoting therapy for prolonged disorders of consciousness: The central role of cerebral glucose metabolism","authors":"Junjie Wang ,&nbsp;Tong Sun ,&nbsp;Yi Zhang ,&nbsp;Xiaoyu Yang ,&nbsp;Yikai Yuan ,&nbsp;Dingkun Zhang ,&nbsp;Junwen Guan","doi":"10.1016/j.brainresbull.2025.111557","DOIUrl":"10.1016/j.brainresbull.2025.111557","url":null,"abstract":"<div><div>With the development of neuroscience, phased achievements have been made in the treatment of patients with prolonged disorders of consciousness(pDoC), but the bottleneck of uncertain clinical efficacy remains to be broken through. This review systematically expounds the core role of glucose metabolism in the wake-promoting mechanism, and for the first time positions glucose metabolism as a common pathway for awakening in pDoC, revealing its \"mechanism explanation - efficacy prediction - treatment navigation\" trinity value. It proposes that glucose metabolism is the energy cornerstone for consciousness recovery, and residual glucose metabolism leads to the localization of therapeutic targets. Completing the metabolic map can guide individualized intervention. Provide theoretical support for the future development of metabolism-oriented and metabolism-responsive neural regulation schemes.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111557"},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102583","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":"Human amniotic mesenchymal stem cell-derived exosome inhibits ferroptosis through the suppression of JNK/MAPK-mediated EGR1 expression in spontaneous intracerebral hemorrhage","authors":"Yiheng Wang,&nbsp;Liangfu Zhou,&nbsp;Kan Xu","doi":"10.1016/j.brainresbull.2025.111553","DOIUrl":"10.1016/j.brainresbull.2025.111553","url":null,"abstract":"<div><h3>Introduction</h3><div>Spontaneous intracerebral hemorrhage (ICH) represents an essential part of stroke, wherein ferroptosis is identified as a critical factor leading to the pathogenesis. Symptomatical treatments are mainly adopted which tend to leave severe neurological deficits. Recently, human amniotic mesenchymal stem cell (hAMSC) therapy has developed rapidly in the field of regenerative medicine, with its secreted exosomes (hAMSC-Exos) regarded as effective alternatives owing to the ability to penetrate the blood-brain barrier. Therefore, we aim to explore the therapeutic efficacy as well as molecular mechanism of hAMSC-Exos in ICH models.</div></div><div><h3>Methods</h3><div>Firstly, hAMSCs and their exosomes were extracted and characterized. Subsequently, the impact of hAMSC-Exos was assessed by evaluating the restoration of neurological function in ICH rat models induced by collagenase VII and in PC12 cells induced by hemin. Moreover, transcriptome sequencing of PC12 cell models identified the potential hub genes and pathways, which were subsequently verified through the western blot among the groups and further examined by the overexpression plasmid transfection and pathway activator treatment.</div></div><div><h3>Results</h3><div>hAMSC-Exos were successfully obtained and characterized. Afterwards, the in vivo and in vitro functional experiments demonstrated the effectiveness of hAMSC-Exos therapy in ICH models by reducing the level of ferroptosis, apoptosis and inflammatory factors and restoring the neurological function. Transcriptome sequencing identified the hub gene <em>Egr1</em> and the key pathway MAPK, which were subsequently verified by the western blot. Specifically, hAMSC-Exos reduced the elevated EGR1 expression and p-JNK/JNK ratio in the ICH model. However, EGR1 overexpression plasmid transfection and anisomycin treatment reactivated ferroptosis in hAMSC-Exos-treated ICH models. Notably, the expression of EGR1 was increased following anisomycin administration.</div></div><div><h3>Conclusion</h3><div>The hAMSC-Exos may attenuate post-ICH ferroptosis and restore neurological function via down-regulating EGR1 mediated by JNK/MAPK in the rat and PC12 cell model of ICH, which might provide new approaches and drug targets in the management of the disease.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111553"},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091082","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":"Aβ oligomers promote lipid droplet accumulation and inflammatory responses in astrocytes but not neurons","authors":"Hui Zhang ,&nbsp;Yazhen Huang ,&nbsp;Wei Wang","doi":"10.1016/j.brainresbull.2025.111556","DOIUrl":"10.1016/j.brainresbull.2025.111556","url":null,"abstract":"<div><div>Lipid droplets (LDs) are dynamic organelles central to cellular lipid homeostasis. Emerging evidence implicates LDs in Alzheimer’s disease (AD) pathogenesis, though their cell-type-specific roles remain poorly defined. Here, we investigated the effects of amyloid-beta oligomers (AβOs) on LDs accumulation, oxidative stress, and inflammatory activation in primary astrocytes and neurons. We found that AβOs selectively triggered robust LDs formation in astrocytes, accompanied by significant increases in triglyceride (TG) and cholesterol (TC) content, and upregulation of the LD-associated protein perilipin 2 (PLIN2). Furthermore, AβOs induced pronounced oxidative stress, evidenced by elevated Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and promoted inflammatory activation via increased secretion of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in astrocytes. By contrast, neurons showed no significant changes in lipid metabolism, oxidative stress, or inflammatory responses under identical treatment conditions. Our results underscore the central role of astrocytes in AβO-induced metabolic and inflammatory dysregulation, revealing a cell-type-specific vulnerability with potential implications for AD pathogenesis. These in vitro findings provide a mechanistic basis for lipid-focused therapeutic strategies, pending further in vivo validation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111556"},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091047","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":"VEGF-A promotes the proliferation and myelination of induced oligodendrocyte progenitor cells in rat spinal cord injury lesions","authors":"Rui Li ,&nbsp;Hongyan Wang ,&nbsp;Ning Sun ,&nbsp;Zhibin Peng ,&nbsp;Yubo Zhang ,&nbsp;Ruixuan Liu ,&nbsp;Jingsong Liu ,&nbsp;Yingwei Zhao ,&nbsp;Yansong Wang","doi":"10.1016/j.brainresbull.2025.111554","DOIUrl":"10.1016/j.brainresbull.2025.111554","url":null,"abstract":"<div><div>Oligodendrocyte precursor cells (OPCs) transplantation represents a promising strategy for promoting spinal cord injury (SCI) recovery, However, the acquisition of allogeneic OPCs from human donors remains challenging due to resource limitation and ethical concerns. Induced OPCs (iOPCs) derived from human Wharton’s jelly cells (h-WJCs) offer a potential alternative for cell transplantation, however, their therapeutic efficacy is hindered by limited cell numbers and in vivo apoptosis. In this study, we identified vascular endothelial growth factor (VEGF-A) as a key factor promoting the proliferation and survival of h-WJC-derived iOPC, as demonstrated by CCK-8 and EdU assay. We further showed that activated T cell supernatant promotes iOPCs proliferation, which is blocked by VEGF-A receptor 2 inhibitor 5408. Transcriptomic analysis revealed the involvement of the MAPK/ERK signaling pathway and phosphorylated protein analysis showed that VEGF-A promotes the phosphorylation of Erk2, effects that attenuated by SU5408. However, transplantation of h-WJCs, iNSCs, and iOPCs alone yielded suboptimal recovery. To address this limitation, we engineered h-WJCs, iNSCs and iOPCs to express exogenous VEGF-A. Among these cells, only h-WJCs exhibited sustained VEGF-A secretion, whereas iNSCs and iOPCs produced low levels of VEGF-A, iOPCs underwent apoptosis, and iNSCs differentiated into GFAP-positive astrocytes. We then co-transplanted iOPCs with h-WJCs expressing VEGF-A into rat SCI. This mixed cell transplantation significantly enhanced cell survival and myelin-binding protein expression. Neuroelectrophysiological recording showed somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) even though no improvement in motor behaviour according to Basso, Beatie, and Bresnahan (BBB) Locomotor Rating Scale. In conclusion, VEGF-A promotes the proliferation and viability of iOPCs in injured spinal cord repair; a transplantation strategy involving mixed-cell grafts supplemented with VEGF-A holds a potential for improving SCI treatment outcomes.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111554"},"PeriodicalIF":3.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091125","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":"SIRT7 inhibits cerebral ischemic injury by inhibiting microglia M1 polarization via desuccinylation of NAMPT","authors":"Ying Cheng ,&nbsp;Kai Zhao ,&nbsp;Jian Li ,&nbsp;Qian Lei ,&nbsp;Gang Zhang ,&nbsp;Xiaoping Gao","doi":"10.1016/j.brainresbull.2025.111551","DOIUrl":"10.1016/j.brainresbull.2025.111551","url":null,"abstract":"<div><div>Cerebral ischemic injury continues to be a leading cause of mortality and disability worldwide. Although Sirtuin 7 (SIRT7), a desuccinylase, is known to regulate protein expression, its role in cerebral ischemia remains unclear. This study utilized a middle cerebral artery occlusion (MCAO) mouse model and an oxygen-glucose deprivation (OGD)-induced microglial model to elucidate the mechanisms of SIRT7. Microglial M1/M2 polarization was assessed via qPCR and immunofluorescence, while underlying mechanisms were analyzed using western blot and co-immunoprecipitation. Our results demonstrated that SIRT7 was significantly downregulated following cerebral ischemic injury. SIRT7 overexpression inhibited OGD-induced M1 polarization, whereas promoting M2 polarization. Mechanistically, SIRT7 mediated nicotinamide phosphoribosyltransferase (NAMPT) desuccinylation and subsequent proteasomal degradation, thereby suppressing M1 polarization and ultimately attenuating brain injury progression. These findings offer novel insights into the regulatory role of SIRT7 in inflammatory responses and suggest that targeting the SIRT7-NAMPT axis could serve as a promising therapeutic strategy for cerebral ischemia-related disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111551"},"PeriodicalIF":3.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079692","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":"Altered glymphatic function and cerebrovascular reactivity in white matter hyperintensities: Insights into cognitive impairment","authors":"Kai Li ,&nbsp;Yueyan Bian ,&nbsp;Yi Xing ,&nbsp;Xiuqin Jia","doi":"10.1016/j.brainresbull.2025.111552","DOIUrl":"10.1016/j.brainresbull.2025.111552","url":null,"abstract":"<div><h3>Objective</h3><div>White matter hyperintensities (WMH) are linked to cognitive impairment and an increased risk of cerebrovascular and neurodegenerative disorders. While the glymphatic system plays a key role in WMH pathophysiology, the relationship between glymphatic function and cerebrovascular reactivity (CVR) in WMH remains unclear. This study aimed to investigate glymphatic function and CVR in WMH patients with varying lesion severity and cognitive status and to explore their relationship with cognitive performance.</div></div><div><h3>Methods</h3><div>A total of 124 participants were categorized into three groups based on Fazekas grade and cognitive function: controls (no/mild WMH), moderate-severe WMH without cognitive impairment, and moderate-severe WMH with cognitive impairment no dementia (WMH-CIND). Glymphatic function was assessed using diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) and global blood oxygen level-dependent cerebrospinal fluid (gBOLD-CSF) coupling from resting-state functional MRI (rs-fMRI). CVR mapping was derived from rs-fMRI, and cognitive performance was evaluated using a comprehensive battery.</div></div><div><h3>Results</h3><div>The ALPS-index showed a stepwise decline with increasing WMH severity and cognitive impairment (p &lt; 0.001). WMH-CIND participants exhibited lower gBOLD-CSF coupling compared with controls (p &lt; 0.05). CVR alterations were localized to frontal and occipital regions. Significant associations were observed between glymphatic indices, region-specific CVR, and cognitive performance across multiple domains.</div></div><div><h3>Conclusion</h3><div>These findings highlight the complex interplay between glymphatic dysfunction, localized CVR impairments, and cognitive decline in WMH. Preserving vascular health and optimizing glymphatic clearance may represent promising approaches for controlling WMH progression and its associated cognitive deficits.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111552"},"PeriodicalIF":3.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085134","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":"Sleep deprivation disrupts vestibular compensation by activating TLR4/NF-κB/NLRP3 signalling in the deafferented vestibular nuclei","authors":"Zhuangzhuang Li ,&nbsp;Jingwei Lai ,&nbsp;Yini Li ,&nbsp;Lingkang Dong ,&nbsp;Jie Li ,&nbsp;Tianjiao Zhou ,&nbsp;Hangdong Shen ,&nbsp;Huaming Zhu ,&nbsp;Dongzhen Yu ,&nbsp;Pengjun Wang ,&nbsp;Haibo Shi","doi":"10.1016/j.brainresbull.2025.111550","DOIUrl":"10.1016/j.brainresbull.2025.111550","url":null,"abstract":"<div><div>We aimed to investigate whether sleep deprivation (SD) affects vestibular compensation and explore the underlying mechanisms. After unilateral labyrinthectomy (UL), adult mice were subjected to 6 h of SD for 5 days. Behavioural tests were performed to evaluate the vestibular recovery. RNA sequencing and bioinformatic analyses were conducted on the deafferented vestibular nuclei (VN) of UL mice with or without SD. Immunofluorescence and western blotting were used to verify the inflammatory responses, neuroplasticity, and pathways in the VN of UL+SD mice. Minocycline and TAK-242 were used to inhibit microglial activation and TLR4, respectively. Our findings suggest that SD significantly impaired vestibular compensation in UL mice. RNA sequencing identified upregulated immune- and inflammation-related pathways in the deafferented VN after SD, which was verified by microglial overactivation. Moreover, neuroplasticity was impaired, and inhibition of microglial proliferation with minocycline partially improved the impaired vestibular compensation during the early stages. Mechanistically, TLR4/NF-κB/NLRP3 pathway activation was predominantly involved in this process, and pharmacological inhibition of TLR4 inhibited NLRP3 activation in microglia and improved SD-induced vestibular compensation delay. Overall, this study illustrates that SD alters neuroplasticity and aggravates microglia-mediated neuroinflammation in deafferented VN by activating TLR4/NF-κB/NLRP3 signalling, which contributes to impaired vestibular compensation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111550"},"PeriodicalIF":3.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069284","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 normative model–based assessment framework for large-scale, multi-site EEG data","authors":"Qiwei Dong ,&nbsp;Yuxi Zhou ,&nbsp;Xiaoyu Xiong ,&nbsp;Pengyu Liu ,&nbsp;Jianfu Li ,&nbsp;Cheng Luo ,&nbsp;Diankun Gong ,&nbsp;Li Dong ,&nbsp;Dezhong Yao","doi":"10.1016/j.brainresbull.2025.111546","DOIUrl":"10.1016/j.brainresbull.2025.111546","url":null,"abstract":"<div><h3>Background</h3><div>Electroencephalography (EEG) overcomes the subjectivity inherent in questionnaire-based and observational assessments. However, most existing EEG-based evaluation methods still impose discrete categorical states onto continuously varying neural dynamics, thereby neglecting the continuity of states. With the rise of neuroscience alliances, challenges such as batch-effects across datasets and inconsistencies introduced by diverse EEG electrode montages have become increasingly prominent. Therefore, a robust assessment framework that accommodates large‑scale, multi‑site EEG data is expected.</div></div><div><h3>Methods</h3><div>A normative model-based assessment framework was developed for large-scale, multi-site EEG data, with attention assessments used as illustrative examples. Normative models are first constructed using EEG features from 1212 young individuals, and quantile ranks are computed. Next, feature selection is performed, and elastic net regression and support vector regression are used to model distributed attention (DA) and focused attention (FA). The results from normative model-based features are compared with original features to demonstrate the advantage of quantile rank features. Finally, the model’s test-retest reliability and generalizability are assessed.</div></div><div><h3>Results</h3><div>The framework identifies statistical differences (<em>q</em> &lt; 0.05) in attention performance between the top and bottom 20 % participants on attention scales. EEG features demonstrated specific patterns related to accuracy and reaction time in both DA and FA tasks. The normative model outperformed in predictive tasks, showing enhanced stability and interpretability. Additionally, the framework demonstrates strong test-retest reliability and robust generalizability (ICC &gt; 0.9).</div></div><div><h3>Conclusion</h3><div>In conclusion, we proposed a normative model–based framework that harmonizes large‑scale, multi‑site EEG data, enabling efficient and reliable attention assessment while demonstrating promise for broader EEG‑based applications.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111546"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063378","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":"Stress-induced regional characteristics of the blood-brain barrier","authors":"Mao-Yang Zhou,&nbsp;Fang Xie,&nbsp;Yun Zhao,&nbsp;Xue Wang,&nbsp;Zhao-Wei Sun,&nbsp;Ling-Jia Qian","doi":"10.1016/j.brainresbull.2025.111548","DOIUrl":"10.1016/j.brainresbull.2025.111548","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) is a neurovascular unit composed of brain microvascular endothelial cells, astrocytes, pericytes, and the basement membrane, playing a critical role in maintaining brain microenvironment homeostasis. However, exposure to external stressors can disrupt the structure and function of the BBB, leading to microenvironmental imbalances and the onset of various neurological disorders. Notably, the impact of stress on the BBB exhibits significant regional heterogeneity across different brain regions, influenced by factors such as the structural and functional characteristics of brain regions, modalities and duration of stress, and sex differences. In recent years, advancements in high-throughput technologies, including single-cell RNA sequencing and spatial transcriptomics, have gradually revealed the molecular features underlying the regional heterogeneity of the BBB under various stress conditions. This review provides a comprehensive overview of the structure and function of the BBB, elaborates the role of BBB in the progression and treatment of neurological disorders, summarizes recent research on stress-induced regional heterogeneity in BBB alterations, and integrates potential contributing factors and the underlying mechanisms. Besides, this review outlines the current applications of new technologies in BBB heterogeneity-related research and the potential values of BBB heterogeneity in clinical therapy, offering new insights and strategies for the diagnosis and treatment of neurological disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"231 ","pages":"Article 111548"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057291","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}