Brain Research Bulletin最新文献

{"title":"Exosomal miR-381–3p derived from astrocytes targets neuronal CDK1 to resist propofol-induced neuronal damage in vitro","authors":"Shengjie Hu ,&nbsp;Yimei Lin ,&nbsp;Jingyi Wu ,&nbsp;Yuejiao Song ,&nbsp;Junmei Wu ,&nbsp;Minmin Yao ,&nbsp;Yan Yang ,&nbsp;Juan Guo ,&nbsp;Changhong Miao ,&nbsp;XiaoDan Han ,&nbsp;Chao Liang","doi":"10.1016/j.brainresbull.2026.111743","DOIUrl":"10.1016/j.brainresbull.2026.111743","url":null,"abstract":"<div><div>Propofol, a widely utilized general anesthetic, can result in developmental neurotoxicity. Previous studies suggest that astrocytes-derived exosomes (ADEs) carrying microRNAs (miRNAs), facilitating neuronal protection. Nevertheless, the underlying mechanism by which miRNAs in ADEs promoting protective effect for propofol-induced neuronal damage remains unknown. Thus, this investigation aims to explore the mechanisms that astrocytes resist propofol-induced neuron injury. Primary neurons and astrocytes were extracted from the hippocampus of mouse embryonic brain. The influence of propofol on neuronal apoptosis were evaluated utilizing a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. To analyze synaptic growth in neurons, immunofluorescence staining for the evaluation of neurite length was conducted. Differentially expressed miRNAs in primary mouse astrocytes were identified through miRNA sequencing, followed by validation using quantitative polymerase chain reaction (qPCR). Luciferase reporter assays, qPCR and western blotting were conducted to explore the effects of miR-381–3p on cyclin-dependent kinase 1 (CDK1) expression. We demonstrated that ADEs mitigated the neuronal damage caused by propofol. MiRNA sequencing revealed a significant upregulation of miR-381–3p within ADEs. Moreover, CDK1 was recognized as the downstream target gene of miR-381–3p. By targeting CDK1, miR-381–3p can counteract propofol-induced neuronal damage. Notably, knockdown of miR-381–3p in astrocytes distinctly diminished the neuroprotective effects of ADEs. Exosomal miR-381–3p derived from astrocytes targets neuronal CDK1 to mitigate propofol-induced neuronal damage.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111743"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035649","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":"Nerol ameliorates cognitive dysfunction in vascular dementia rats by inhibiting mitochondrial oxidative stress and reducing hippocampal senescence","authors":"Jing Yang ,&nbsp;Qian-qian Niu ,&nbsp;Na Liu ,&nbsp;Bo Wang ,&nbsp;Ya-jun Shen ,&nbsp;De-sheng Liu ,&nbsp;Xiao-wen Li ,&nbsp;Mo-li Zhu ,&nbsp;Qian-qian Wang ,&nbsp;Ya-qi Guo","doi":"10.1016/j.brainresbull.2026.111753","DOIUrl":"10.1016/j.brainresbull.2026.111753","url":null,"abstract":"<div><div>Vascular dementia (VaD) is a neurodegenerative disease caused by chronic cerebral hypoperfusion and is mainly characterized by cognitive dysfunction. This study established a VaD rat model using permanent bilateral common carotid artery occlusion (2-VO), administered different doses of nerol for 8 weeks, and evaluated cognitive function using the Morris water maze and Y-maze tests, while systematically analyzing hippocampal neuronal structure, senescence, mitochondrial function, oxidative stress, and apoptosis-related changes. The results showed that nerol improved spatial learning, memory ability, and exploratory behavior in VaD rats, and alleviated hippocampal neuronal structural damage and dendritic degeneration. At the same time, nerol reduced the number of senescence-associated β-galactosidase–positive and TUNEL-positive cells and downregulated the expression of p53 and p21. Mechanistically, nerol inhibited NOX2/NOX4-mediated reactive oxygen species production, enhanced antioxidant capacity, stabilized mitochondrial membrane potential, and suppressed DRP1/FIS1-mediated abnormal mitochondrial fission, thereby potentially attenuating oxidative stress–related neuronal senescence and apoptosis and improving cognitive function. These findings provide experimental evidence supporting the potential therapeutic value of nerol in vascular dementia.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111753"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096675","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":"Suppression of the PI3K/AKT/mTOR signaling pathway by PDYN alleviates sepsis-associated encephalopathy in mice","authors":"Ao Li ,&nbsp;Shujuan Qu ,&nbsp;Shengfeng Wang ,&nbsp;Qiong Guo ,&nbsp;Sinian Tan ,&nbsp;Mao Peng ,&nbsp;Lin Liu","doi":"10.1016/j.brainresbull.2026.111734","DOIUrl":"10.1016/j.brainresbull.2026.111734","url":null,"abstract":"<div><h3>Background</h3><div>Microglial pyroptosis-mediated neuroinflammation is a key pathogenic mechanism in Sepsis-Associated Encephalopathy (SAE). However, the role of prodynorphin (PDYN) in SAE and the relationship between PDYN and microglial pyroptosis remain unknown.</div></div><div><h3>Methods</h3><div>Mice were subjected to cecal ligation and puncture (CLP) or sham surgery. Microglial cells were treated with lipopolysaccharide (LPS) <em>in vitro</em>. Cognitive function was assessed using the Morris water maze, novel object recognition, and open field tests. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining was used to observe glial apoptosis; Nissl staining was used to observe microglial infiltration; H&amp;E staining was used to detect histopathological changes. Pyroptosis and the expression levels of relevant signaling molecules were assessed by Western blot analysis.</div></div><div><h3>Results</h3><div>PDYN protected against neuronal damage and cognitive impairment in septic mice. PDYN inhibits microglial pyroptosis and secretion of inflammatory cytokines <em>in vivo</em> and <em>in vitro</em>. Further examination revealed that PDYN inhibits microglial pyroptosis by inhibiting the PI3K/AKT/mTORC pathway. Moreover, the PI3K activator 740Y-P promoted microglial pyroptosis by activating the PI3K/AKT/mTORC pathway.</div></div><div><h3>Conclusion</h3><div>This study reveals, for the first time, that PDYN exerts neuroprotective effects in SAE by suppressing microglial pyroptosis through inhibition of the PI3K/AKT/mTOR signaling pathway. These findings identify PDYN and the PI3K/AKT/mTOR-pyroptosis axis as novel therapeutic targets for SAE, providing a mechanistic foundation for developing adjunctive neuroprotective strategies alongside standard sepsis care.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111734"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975645","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":"Kininogen-1 modulates cGMP-PKG signaling to alleviate inflammatory neuronal injury in intracerebral hemorrhage","authors":"Yuan Wang ,&nbsp;Jing Zhao ,&nbsp;Kaijie Wang ,&nbsp;Shuwei Wang ,&nbsp;Jie Li ,&nbsp;Chaopeng Xu ,&nbsp;Haoyu Wang ,&nbsp;Jianzhong Cui","doi":"10.1016/j.brainresbull.2026.111740","DOIUrl":"10.1016/j.brainresbull.2026.111740","url":null,"abstract":"<div><h3>Objective</h3><div>Although the pathological mechanisms underlying intracerebral hemorrhage (ICH) have been widely explored, the contribution of kininogen-1 (Kng1) to inflammation-associated neuronal damage has not been fully elucidated. This study was designed to investigate the functional involvement of Kng1 and the cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling cascade in inflammation-driven neuronal injury following cerebral hemorrhage.</div></div><div><h3>Methods</h3><div>Bioinformatics analyses based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were employed to identify Kng1 and the cGMP-PKG pathway as key candidates. An in vivo ICH model was generated by intracerebral injection of autologous blood, while an in vitro hemorrhagic injury model was established by treating neuronal cells with hemoglobin chloride. Levels of inflammatory mediators and gene expression were determined using enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and reverse transcription-quantitative polymerase chain reaction. Neurological impairment and cerebral edema were evaluated through behavioral deficit scoring and brain water content analysis, respectively.</div></div><div><h3>Results</h3><div>Kng1 protein levels were markedly increased in the serum of patients with ICH as well as in experimental hemorrhage models, and this elevation was closely associated with enhanced neuroinflammatory responses. Suppression of Kng1 expression significantly alleviated neurological dysfunction, reduced cerebral edema, mitigated inflammatory activation, and limited neuronal apoptosis in ICH rats. Further mechanistic investigations demonstrated that Kng1 modulates the cGMP-PKG signaling axis, as pharmacological stimulation of cGMP or PKG reversed the protective effects induced by Kng1 silencing. Consistent findings from both animal and cellular rescue experiments indicated that Kng1 aggravates neuronal injury after ICH by activating cGMP-PKG-dependent inflammatory signaling pathways.</div></div><div><h3>Conclusion</h3><div>Kng1 regulates the cGMP-PKG signaling pathway, influencing neuronal cell injury induced by the inflammatory response in ICH conditions. These findings suggest Kng1 as a potential therapeutic target for mitigating ICH-induced neuronal damage.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111740"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017461","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":"Adaptive immune dysregulation in depression: Cross-species evidence of CD4+ T cell dysfunction and pro-inflammatory pathway activation","authors":"Liekui Hu ,&nbsp;Zhaozhi Qiu ,&nbsp;Zhifu Ai ,&nbsp;Rui Liu ,&nbsp;Bike Zhang ,&nbsp;Huizhen Li","doi":"10.1016/j.brainresbull.2026.111752","DOIUrl":"10.1016/j.brainresbull.2026.111752","url":null,"abstract":"<div><div>The association between central adaptive immunity and depression remains highly debated. In this study, we systematically assessed the role of adaptive immune mechanisms in depression using a mouse model of chronic unpredictable mild stress (CUMS) and the peripheral blood of patients with depression. The behavioral results demonstrated that the CUMS mice exhibited typical depression-like behaviors. Subsequent transcriptomic analysis of the hippocampus identified 203 differentially expressed genes (DEGs), of which CD4 expression was significantly downregulated. Furthermore, DEGs were enriched in the tumor necrosis factor (TNF) and interleukin (IL)-17 signaling pathways. Validation experiments further corroborated the hypothesis that the CD4 gene in the hippocampal region of CUMS mice was reduced in parallel with the protein levels. Immunocorrelation assays revealed a decrease in intercellular cell adhesion molecule-1 expression in the hippocampus, along with an increase in vascular cell adhesion molecule-1 expression. These changes were accompanied by cytokine level disruption in CUMS mice. A total of 391 DEGs were identified in the transcriptome sequencing of peripheral blood CD4⁺T cells from patients with depression using the Gene Expression Omnibus database. These DEGs were significantly associated with the PI3K-AKT, IL-17, and TNF signaling pathways. Immune checkpoint analysis revealed elevated PDCD1 and decreased TIGIT expression in CD4⁺T cells of the patients. The integration of animal models and clinical data revealed a convergent pattern of findings, indicating CD4⁺ T-cell dysfunction and the activation of pro-inflammatory pathways as immune features shared across species in depression. This provides a novel rationale for targeted immunomodulatory treatment of depression.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111752"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090181","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":"Dendrobine attenuates postoperative cognitive dysfunction by inhibiting Runx1-mediated NF-κB signaling pathway","authors":"Dong Ji ,&nbsp;Qingyu Sun ,&nbsp;Chengcheng Zhang ,&nbsp;Mingyi Zang ,&nbsp;Wei Xiao ,&nbsp;Jie Liu ,&nbsp;Xiaohua Fan ,&nbsp;Hongbing Wang","doi":"10.1016/j.brainresbull.2026.111746","DOIUrl":"10.1016/j.brainresbull.2026.111746","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) in older adults is strongly linked to neuroinflammation driven by microglial activation and NF-κB signaling. Runx1 has emerged as an upstream regulator of NF-κB, but its role in POCD is unknown. Dendrobine, a sesquiterpenoid alkaloid from Dendrobium species, exhibits anti-inflammatory and neuroprotective activity.</div></div><div><h3>Methods</h3><div>POCD was induced in aged C57BL/6 mice via sevoflurane anesthesia combined with exploratory laparotomy. Dendrobine (10 or 20 mg/kg) was administered, and cognitive outcomes were evaluated by Morris Water Maze and Novel Object Recognition. RNA sequencing, Western blotting, immunofluorescence, and in vitro microglia-neuron co-culture systems were employed to investigate inflammatory responses, apoptosis, synaptic plasticity, and signaling pathway activation. Functional roles of Runx1 were validated via siRNA knockdown, pharmacological inhibition (Ro5–3335), and overexpression in BV2 cells.</div></div><div><h3>Results</h3><div>Dendrobine improved spatial and recognition memory in POCD mice, reduced hippocampal microglial activation, proinflammatory cytokine expression (TNF-α, IL-1β, IL-6), and neuronal apoptosis while enhancing synaptic protein levels (BDNF, PSD95, SYN1). Transcriptomic and KEGG analyses revealed suppression of NF-κB signaling by dendrobine, with Runx1 identified as an upstream modulator. Dendrobine downregulated Runx1 expression in vivo and in vitro. Runx1 inhibition enhanced dendrobine’s anti-inflammatory effects, whereas RUNX1 overexpression abolished them.</div></div><div><h3>Conclusion</h3><div>Dendrobine ameliorates POCD by inhibiting the Runx1/NF-κB signaling pathway, suppressing neuroinflammation, promoting synaptic resilience, and preventing neuronal apoptosis. Runx1 appears to act as a key upstream mediator of NF-κB signaling in POCD. Targeting the Runx1/NF-κB axis represents a promising strategy for perioperative neuroprotection.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111746"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090717","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":"Mapping structural disconnection and transcriptomic signatures in Alzheimer’s disease with MIND networks","authors":"Yongsheng Wu ,&nbsp;Hao Zhang ,&nbsp;Junyu Qu ,&nbsp;Rui Zhu ,&nbsp;Guihua Xu ,&nbsp;Wenwen Xu ,&nbsp;Guizhen Yan ,&nbsp;Jianhong Yang ,&nbsp;Jiaxiang Xin ,&nbsp;Yi Li ,&nbsp;Dawei Wang ,&nbsp;for Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1016/j.brainresbull.2026.111737","DOIUrl":"10.1016/j.brainresbull.2026.111737","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer’s disease (AD) is increasingly conceptualized as a disconnection syndrome involving widespread alterations in large-scale brain networks. Previous studies using morphometric similarity networks (MSNs) have revealed broad structural and transcriptomic changes, yet vertex-level structural disconnection and its molecular basis remain poorly understood. We applied morphometric inverse divergence (MIND), an innovative approach for fine-grained mapping of structural disconnection and its transcriptomic correlates in AD.</div></div><div><h3>Methods</h3><div>Utilizing two independent datasets: [ADNI (219 AD, 219 cognitively normal, CN) and the Qilu dataset (100 AD, 137 CN)], we mapped robust MIND network alterations in AD patients and examined their associations with cognitive performance and biomarker quantifications. Additionally, we linked MIND connectome to spatial gene expression using partial least squares regression, followed by gene enrichment analysis to identify relevant biological pathways. Finally, to validate the clinical utility of MIND, a residual deep neural network (ResDNN) was developed to compare its diagnostic performance against MSNs in distinguishing AD from CN.</div></div><div><h3>Results</h3><div>Significantly decreased MIND degree was identified in the bilateral frontal, lateral occipital, and posterior temporal lobes (P _FDR &lt; 0.05), positively correlating with MMSE score and FDG-PET SUVR (all P &lt; 0.001). Conversely, increased MIND degree was observed in the bilateral cuneus, entorhinal, lingual, and parahippocampal regions (P _FDR &lt; 0.05), negatively correlating with cognition assessment, CSF Aβ-42 levels and FDG-PET SUVR (all P &lt; 0.001). These AD-related MIND alterations were spatially correlated with gene expression profiles crucial for synaptic function, neurotransmission, and metabolic regulation. Importantly, MIND achieved superior diagnostic efficacy (AUC=0.90/0.88 in ADNI/Qilu) over MSNs.</div></div><div><h3>Conclusions</h3><div>We mapped a robust pattern of structural disconnection in Alzheimer's disease with MIND approach and associate it with particular transcriptomic signatures. These findings not only improve our mechanistic understanding of AD as a disconnection syndrome but also demonstrate MIND as a sensitive tool for identifying disease-specific alterations, holding promise for future mechanistic and clinical investigations into AD pathology.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111737"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997323","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":"Sodium acetate and sodium butyrate ameliorate postoperative cognitive dysfunction in aged rats by suppressing inflammation and ferroptosis via inhibition of the cGAS-STING signaling pathway","authors":"Kai-Hui Zeng ,&nbsp;Li-Ping Yu ,&nbsp;Zhen Chen ,&nbsp;Xiang Li","doi":"10.1016/j.brainresbull.2025.111677","DOIUrl":"10.1016/j.brainresbull.2025.111677","url":null,"abstract":"<div><h3>Background</h3><div>Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication in elderly patients following surgery. Short-chain fatty acids (SCFAs), including acetate and butyrate, exert anti-inflammatory and antioxidant properties; however, their potential neuroprotective roles in POCD remain largely unexplored. Hence, this study investigated whether sodium acetate (NaA) and sodium butyrate (NaB) ameliorate POCD in aged rats and elucidated the underlying mechanisms.</div></div><div><h3>Methods</h3><div>A POCD model was established in aged male Sprague-Dawley rats by exploratory laparotomy under isoflurane anesthesia. NaA or NaB was administered orally prior to surgery. Cognitive function was assessed using the Morris water maze (MWM), Y-maze, and novel object recognition (NOR) tests. Hippocampal inflammatory responses were assessed by measuring TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. Ferroptosis was evaluated by measuring reactive oxygen species (ROS), malondialdehyde (MDA), Fe²⁺ content, antioxidant activities (SOD, GPx, GSH), and the expression of ferroptosis-related genes (TfR1, DMT1, FTH1, FTL, GPX4, and SLC7A11). Activation of the cGAS-STING signaling pathway was examined via Western blot and ELISA. In addition, hippocampal cGAS was overexpressed to assess its causal role.</div></div><div><h3>Results</h3><div>Both NaA and NaB significantly improved cognitive performance in aged POCD rats, as evidenced by enhanced spatial learning and memory in the MWM, increased spontaneous alternation in the Y-maze test, and a higher recognition index in the NOR test. Mechanistically, NaA and NaB markedly suppressed hippocampal inflammation, as evidenced by decreased TNF-α, IL-1β, IL-6, IL-17A, and iNOS levels. NaA and NaB also attenuated ferroptosis, indicated by decreased ROS, MDA, and Fe²⁺ levels, restored SOD, GPx, and GSH activities, upregulated GPX4, SLC7A11, FTH1, and FTL expression, and downregulated TfR1 and DMT1 expression in the hippocampus of aged POCD rats. Furthermore, NaA and NaB inhibited activation of the cGAS-STING signaling pathway in the hippocampus of aged POCD rats. Importantly, hippocampal cGAS overexpression reversed the anti-inflammatory, anti-ferroptotic, and cognitive protective effects of NaA and NaB.</div></div><div><h3>Conclusion</h3><div>NaA and NaB ameliorate POCD in aged rats by mitigating hippocampal inflammation and ferroptosis, potentially via inhibition of the cGAS-STING signaling pathway.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111677"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699625","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":"Regulation of angiogenesis in cerebral ischemic rats through ceRNA networks and its impact on cerebral ischemic stroke prognosis","authors":"Wenfeng Cao ,&nbsp;Mingyue Wang ,&nbsp;Wen Chai ,&nbsp;Chaoqun Luo ,&nbsp;Yanmei Wang ,&nbsp;Xinhua Zhou ,&nbsp;Jie Li ,&nbsp;Lingjuan Li","doi":"10.1016/j.brainresbull.2025.111703","DOIUrl":"10.1016/j.brainresbull.2025.111703","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemic stroke (CIS) represents a major cerebrovascular disorder characterized by high incidence and disability rates, significantly compromising patient quality of life and survival. Angiogenesis demonstrates potential for improving post-ischemic cerebral blood flow and reducing infarct volume, though its regulatory mechanisms require further elucidation.</div></div><div><h3>Methods</h3><div>We established a permanent focal middle cerebral artery occlusion (pMCAO) rat model and performed whole transcriptome sequencing. Differential expression analysis identified dysregulated long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Regulatory networks (circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA) were constructed using differential expression data and public databases. mRNAs within networks underwent functional enrichment and protein-protein interaction (PPI) analysis to investigate angiogenic mechanisms.</div></div><div><h3>Results</h3><div>Ischemia-hypoxia altered circRNA, lncRNA, and miRNA expression profiles, modulating angiogenesis through specific pathways. The circRNA/lncRNA-miRNA-mRNA networks implicated angiogenesis-related pathways including Cytokine-cytokine receptor interaction and cAMP signaling pathway. Key miRNAs (rno-miR-665, rno-novel-108-mature, rno-novel-82-mature) demonstrated strong angiogenic associations in the ischemia-hypoxia model.</div></div><div><h3>Conclusions</h3><div>This study delineates lncRNA, circRNA, and miRNA regulatory functions in ischemia-hypoxia through network construction, highlighting candidate therapeutic targets. These findings provide novel research directions for promoting angiogenesis and improving CIS prognosis.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111703"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848847","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":"The impact of sleep deprivation on dynamic functional connectivity of the brain: Based on alertness task performance","authors":"Anping Ouyang ,&nbsp;Xinxin Lin ,&nbsp;Tian Zhang ,&nbsp;Jiayao Li ,&nbsp;Chenxi Li ,&nbsp;Lingling Wang ,&nbsp;Zhiyuan Cao ,&nbsp;Xuqian Diao ,&nbsp;Wei He ,&nbsp;Qianqian Dong ,&nbsp;Jun Jiang ,&nbsp;Peng Fang","doi":"10.1016/j.brainresbull.2025.111712","DOIUrl":"10.1016/j.brainresbull.2025.111712","url":null,"abstract":"<div><div>Sleep deprivation (SD) impairs mood and cognition, yet its dynamic neural mechanisms remain unclear. Forty healthy adults (30-h SD) completed mood assessments, resting-state fMRI (rs-fMRI), and psychomotor vigilance task (PVT) tests at baseline and post-SD. Using dynamic functional connectivity (dFC) with sliding windows and k-means clustering, we identified two recurrent whole-brain states: (i) an economical state with sparse, weaker global coupling and (ii) a maladaptive compensatory state with globally strengthened synchronization. SD increased both the fraction of windows and mean dwell time (MDT) of the maladaptive state. Across participants, PVT lapses correlated positively with the maladaptive state’s MDT and fraction of windows and negatively with those of the economical state. Finally, we built an interpretable predictive model of PVT lapses using competitive adaptive reweighted sampling partial least-squares regression (CARS-PLSR), which highlighted connections within the dorsal attention network (DAN) as key predictors. These findings link behavioral impairment to altered brain-state dynamics and provide a sparse, testable feature set that can support early risk stratification and intervention for SD-related cognitive decline.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111712"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948025","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}