Brain Research Bulletin最新文献

{"title":"Niosome-encapsulated sodium butyrate enhances blood-brain barrier integrity and reduces neuroinflammation in a rat model of ischemic stroke","authors":"Nasim Naseri ,&nbsp;Mohammad Reza Bigdeli ,&nbsp;Fatemeh Mortazavi Moghadam ,&nbsp;Bahram Kazemi","doi":"10.1016/j.brainresbull.2026.111736","DOIUrl":"10.1016/j.brainresbull.2026.111736","url":null,"abstract":"<div><div>Ischemic stroke remains a major cause of mortality and disability worldwide, accompanied by severe inflammation and blood-brain barrier (BBB) disruption. Sodium butyrate (SB), a promising therapeutic agent, has been extensively studied for its anti-inflammatory effects in neurological disorders. However, its bioavailability is limited by low bioavailability and a short half-life. To address this challenge, SB-loaded niosome nanoparticles (NSB) were synthesized using the thin-film hydration method with a 1:1 ratio of Tween-60 and cholesterol and tested for physicochemical properties. NSB exhibited a particle size of 81.59 nm, PDI of 0.276, zeta potential of –3.36 mV, entrapment efficiency of 94.11 %, and 62.7 % reduction in cumulative release over 24 h. Also, Field-emission scanning electron microscopy (FE-SEM) confirmed the spherical morphology and polydispersity of the nanoparticles. To investigate the therapeutic efficacy of NSB, male Wistar rats were divided into four groups: sham, control, SB, and NSB. Treatments were administered intraperitoneally, followed by middle cerebral artery occlusion (MCAO). Neurobehavioral assessments, histopathological alterations, BBB permeability, biochemical factors, and relative mRNA expression of <em>Tnf-α</em>, <em>Il-1β</em>, <em>Claudin-5</em>, <em>Zo-1</em>, and <em>Mmp-9</em> were measured 24 h post-reperfusion. NSB administration significantly reduced infarct volume, neurobehavioral deficits, BBB permeability, and histopathological damage compared to free SB. Additionally, NSB increased the enzyme activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde levels and mRNA expression of proinflammatory cytokines. Furthermore, NSB preserved BBB integrity by reducing <em>Mmp-9</em> expression while upregulating <em>Claudin-5</em> and <em>Zo-1</em>. These findings suggest niosomes as a promising nano-formulation to enhance SB bioavailability and neuroprotective efficacy in ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111736"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994219","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 brain dynamic in cirrhotic patients without overt hepatic encephalopathy: State and trait features","authors":"Chao Ju ,&nbsp;Longtao Yang ,&nbsp;Zhongshang Dai ,&nbsp;Yisong Wang ,&nbsp;Yingxia Zhou ,&nbsp;Jun Liu","doi":"10.1016/j.brainresbull.2026.111724","DOIUrl":"10.1016/j.brainresbull.2026.111724","url":null,"abstract":"<div><div>Neurocognitive impairment, a prevalent complication in cirrhosis, correlates with disruptions in static functional connectivity(FC) of the brain. This study aims to explore altered spatiotemporal properties of blood oxygen-level dependent(BOLD) signals and elucidate their association with neurocognitive changes in cirrhotic patients. Between March 2023 and February 2025, we recruited 77 cirrhotic patients and 66 healthy controls(HCs) accompanied by resting-state functional magnetic resonance imaging(rs-fMRI) acquisition. Neurocognitive function was evaluated by psychometric hepatic encephalopathy score(PHES). The hidden Markov model(HMM) was used to explain variations in rs-fMRI averaged functional activity(AFA) and FC across the whole-brain by using a set of 5 unique recurring states. This study assessed the stability between different groups by comparing the time spent in each state and the mean duration of visits to each state. Mann<img>Whitney U tests, Kruskal Wallis H test, chi-squared test, correlation analysis. After Bonferroni correction, cirrhotic patients with minimal hepatic encephalopathy(MHE) showed significantly higher temporal stability and proportional time spent in state#1 characterized by lower AFA of frontoparietal network(FPN) and subcortical network and higher AFA of visual network (VN), as well as have lower fractional occupancy(FO) and averaged lifetime(ALT) in state#5, which is characterized by weaker within-network FC and lower AFA of limbic network(LN), salience network(SN), somatosensory motor network(SMN), and default mode network(DMN). We observed a significant positive correlation(Bonferroni corrected) between dynamic properties in state#5 and PHES performance. These findings suggest that disrupted brain functional synchrony across time is present in MHE and is linked to cognitive impairment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111724"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951553","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":"Purα overexpression mitigates neonatal hypoxic-ischemic brain damage by inhibiting neuronal pyroptosis via the P2X7R/NLRP3/Caspase-1 pathway","authors":"Da Zheng ,&nbsp;Hui Zhang ,&nbsp;Yi-Kai Zou ,&nbsp;Jiao-Yang Yang ,&nbsp;Shu-Yi He ,&nbsp;Hai-Jing Peng ,&nbsp;Jian-Xia Liu ,&nbsp;Shao-Hua Qi ,&nbsp;Jia-Wei Min","doi":"10.1016/j.brainresbull.2026.111726","DOIUrl":"10.1016/j.brainresbull.2026.111726","url":null,"abstract":"<div><div>Hypoxic-ischemic brain damage (HIBD) is a common neonatal disorder that often leads to permanent neurological sequelae. Neuronal pyroptosis, a pro-inflammatory form of programmed cell death, has been increasingly recognized as a key contributor to neuronal damage and subsequent neurological deficits in HIBD. However, effective therapeutic strategies for HIBD remain limited, highlighting the urgent need to identify novel therapeutic targets. Purine-rich element-binding protein α (Purα) is a multifunctional DNA/RNA-binding protein involved in gene transcription and nervous system regulation. However, its role in neonatal HIBD has not been defined. Here, we investigated the neuroprotective effects of Purα in both <em>in vivo</em> and <em>in vitro</em> models of HIBD. We found that endogenous Purα protein levels were markedly reduced in brain tissue from HI-challenged neonatal mice and in primary cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Purα overexpression effectively reduced cerebral infarction, alleviated neuronal injury, attenuated brain atrophy, and improved neurological outcomes in neonatal HIBD mice. In cultured neurons, Purα overexpression significantly increased cell viability and reduced cell death following OGD/R. RNA sequencing identified purinergic 2X7 receptor (P2X7R) as a potential downstream target of Purα, consistent with P2X7R’s established role in pyroptosis regulation. Mechanistic studies further demonstrated that Purα overexpression suppressed P2X7R expression and inhibited activation of the NLRP3/Caspase-1 pathway, as indicated by reduced levels of P2X7R, NLRP3, Caspase-1, cleaved Caspase-1, GSDMD-N, and IL-1β. Collectively, these findings reveal a novel role for Purα in mitigating neuronal pyroptosis via regulation of the P2X7R/NLRP3/Caspase-1 pathway and support Purα as a promising therapeutic target for neonatal HIBD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111726"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976336","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 cerebellar morphological similarity network correlates with cognitive decline and cerebrospinal fluid biomarkers in mild Alzheimer’s disease: a 7 T MRI study","authors":"Weiwei Zhang ,&nbsp;Haokun Liu ,&nbsp;Long Qian ,&nbsp;Cong Zhang ,&nbsp;Dongcui Wang ,&nbsp;Keying Fang ,&nbsp;Ruiting Chen ,&nbsp;Bin Jiao ,&nbsp;Lu Shen ,&nbsp;Weihua Liao","doi":"10.1016/j.brainresbull.2026.111731","DOIUrl":"10.1016/j.brainresbull.2026.111731","url":null,"abstract":"<div><h3>Backgroud</h3><div>Recent neuroimaging research emphasized cerebellar atrophy and alternation of functional connections in Alzheimer’s disease (AD), fewer studies have focus on the cerebellar subfield and its structural network reorganization. This study aimed to explore the utility of 7 T MRI in assessing cerebellar subfield volumes, morphological similarity network (MSN) and their correlation with cognitive decline and cerebrospinal fluid (CSF) biomarkers in mild AD.</div></div><div><h3>Methods</h3><div>Cerebellar subfield segmentation and individual level MSNs construction were performed using high-resolution structural 7 T MRI data in 30 AD of mild stage and 30 healthy normal controls (NCs). Subfield volumes and topological parameters of the resulting graphs were compared between groups. Correlations between altered MSN metrics and cognitive measurement, CSF biomarkers were further analyzed in AD group.</div></div><div><h3>Results</h3><div>Compared to NCs, AD patients exhibited salient vermis VIIb and vermis VIIIa atrophy and significantly large-scale topological alterations of nodal properties of cerebellar MSN, predominantly in the posterior lobes (lobe VI-IX). The global network metrics were relatively preserved, despite the increased global assortativity. Altered structural network properties of lobule VIII, vermis IX and crus II were significantly associated with cognitive decline and CSF Aβ42 and p-tau181 levels in AD.</div></div><div><h3>Conclusions</h3><div>Our study emphasizes the crucial role of alterations in morphological connectivity beyond cerebellar atrophy in early AD using 7 T MRI. Structural network alterations in lobule VIII, vermis IX and crus II demonstrated significantly correlation with clinical variables, indicating their potential as sensitive imaging markers and therapeutic targets for AD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111731"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035650","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":"MAF1 loss protects against ischemic cerebral injury by attenuating NLRP3-mediated pyroptosis","authors":"Xue Gao,&nbsp;Hanzhi Wang,&nbsp;Lingting Jin,&nbsp;Shumeng Li,&nbsp;Gang Li,&nbsp;Can Cui,&nbsp;Yingying Han","doi":"10.1016/j.brainresbull.2026.111732","DOIUrl":"10.1016/j.brainresbull.2026.111732","url":null,"abstract":"<div><h3>Background</h3><div>Acute ischemic stroke (AIS) is the second leading cause of death worldwide and is associated with high rates of disability and mortality. Emerging evidence indicates that the transcriptional regulator MAF1 may play an important role in neurological diseases by modulating the NLRP3 signaling pathway. Previous studies suggest the transcriptional regulator MAF1 may play an important role in neurological diseases through regulating NLRP3 pathway. However, its role in ischemic cerebral injury remains unclear. This study aims to reveal the key role and mechanisms of MAF1 in AIS.</div></div><div><h3>Methods</h3><div>Using transient middle cerebral artery occlusion (tMCAO) model, the sensorimotor function of mice after modeling was evaluated by behavioral methods and changes of MAF1 expression were investigated by Polymerase Chain Reaction (PCR), Western blot and Immunofluorescence (IF) staining. The oxygen glucose deprivation/reperfusion (OGD/R) model was used as cell model for in vitro verification. Stereotactic injection of AAV-hsyn-shMAF1 was used to assess the effect of MAF1 knockdown on the improvement of neurological function and infarct volume in stroke mice. RNA sequencing was performed to identify differentially expressed genes between OGD/R-Lenti-shMAF1 and OGD/R-Lenti-SCR groups. Western blot analysis was further applied to examine molecular alterations in the downstream NLRP3 pathway.</div></div><div><h3>Results</h3><div>Expression of the transcription factor MAF1 was upregulated in AIS and conditional Conditional knockdown of MAF1 in the tMCAO mouse model alleviated neurological deficits and reduced infarct volume. RNA sequencing revealed altered expression of NLRP3-related pyroptosis proteins and pathways following MAF1 knockdown in OGD/R-treated primary neurons. Downregulation of MAF1 led to expression changes of NLRP3 inflammasome/pyroptosis pathways in both tMCAO mouse and OGD/R cell models.</div></div><div><h3>Conclusions</h3><div>MAF1 expression was significantly increased in animal and cellular models of AIS. Knockdown of MAF1 improved neurological function after AIS and the protective effect is related to the regulation of the NLRP3 inflammasome/pyroptosis pathway. These findings elucidated a critical role and mechanistic insight for MAF1 in AIS pathogenesis, highlighting its potential as a therapeutic target for ischemic stroke treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111732"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975644","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":"TCF7L2 transcriptionally regulates C1QB to exacerbate synaptic pruning-dependent neuronal injury in the epileptic hippocampus","authors":"Lulu Wu ,&nbsp;Yuping Huang ,&nbsp;Xinyu Wang ,&nbsp;Ting Tian ,&nbsp;Dandan Feng ,&nbsp;Guoping Zhou","doi":"10.1016/j.brainresbull.2026.111730","DOIUrl":"10.1016/j.brainresbull.2026.111730","url":null,"abstract":"<div><div>Epilepsy represents one of the most prevalent and debilitating chronic neurological disorders. While the complement component 1q subcomponent B (C1QB) has been implicated in synaptic pruning and is associated with various neurological diseases, including epilepsy, the transcriptional regulatory mechanisms of the <em>C1QB</em> gene in epilepsy remain poorly understood. Here, we identified transcription factor 7-like 2 (<em>TCF7L2</em>) as a novel upstream transcriptional regulator of <em>C1QB</em> gene. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays confirmed the direct binding of <em>TCF7L2</em> to the <em>C1QB</em> promoter region and its positive regulatory effect on <em>C1QB</em> expression in vitro. Using a kainic acid-induced epilepsy model in male C57BL/6 mice, we demonstrated a significant upregulation of both <em>Tcf7l2</em> and <em>C1qb</em> in the hippocampal region, which was accompanied by microglial activation and neuronal damage. Notably, the lentivirus-mediated specific knockdown of <em>Tcf7l2</em> effectively reversed the overexpression of <em>C1qb</em>, attenuated microglial activation, and ameliorated neuronal injury in epileptic mice. Our study establishes the <em>TCF7L2-C1QB</em> regulatory axis and demonstrates its pathogenic role in epilepsy, suggesting that targeting this pathway may offer a novel therapeutic strategy for epilepsy treatment.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111730"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975646","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":"Alkaloids and flavonoids of Solanaceae: Mechanisms of action in neurodegenerative diseases","authors":"Qiushi Yin ,&nbsp;Mingzhen Hu ,&nbsp;Wei Li ,&nbsp;Peng Cheng ,&nbsp;Yuqing Liu ,&nbsp;Long Liu ,&nbsp;Lin Chen ,&nbsp;Qin Ru ,&nbsp;Yuxiang Wu","doi":"10.1016/j.brainresbull.2026.111716","DOIUrl":"10.1016/j.brainresbull.2026.111716","url":null,"abstract":"<div><div>Neurodegenerative diseases (e.g., Alzheimer's disease [AD], Parkinson's disease [PD], Huntington's disease [HD]) pose a serious threat to human health. Current therapeutic approaches have limitations such as significant side effects and limited efficacy, making natural plant active ingredients an emerging research focus in this field. Solanaceae plants are widely distributed worldwide, rich in secondary metabolites such as alkaloids and flavonoids, and have long been used in traditional medicine. This review systematically summarizes the structural characteristics of Solanaceae-derived alkaloids (e.g., nicotine[NI], atropine[ATP], scopolamine[SCO]) and flavonoids (e.g., quercetin[QR], luteolin[LUT], kaempferol[KAE], anthocyanidin[ACN]), as well as their therapeutic potential and core mechanisms of action against the three major neurodegenerative diseases — including multi-target regulatory pathways such as antioxidative stress, inhibiting neuroinflammation, regulating neurotransmitter balance, preventing abnormal protein aggregation, and suppressing neuronal apoptosis. Additionally, this review analyzes the challenges faced by these natural products in extraction and purification, bioavailability, target selectivity, and clinical translation, and prospects the potential of promoting their clinical application through technological breakthroughs such as synthetic biology and nanodelivery systems. This review indicates that Solanaceae-derived secondary metabolites provide an important resource for the development of safe and effective therapeutic drugs for neurodegenerative diseases, with broad application value.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111716"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976335","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":"Inhibiting H3K18 lactylation in microglia aggravates white matter injury after intracerebral hemorrhage in mice","authors":"Bing Jiang ,&nbsp;Lin Li ,&nbsp;Ye Yuan ,&nbsp;Zhongyi Zhang ,&nbsp;Yuxin Xie ,&nbsp;Linhui Zhang ,&nbsp;Yihao Tao ,&nbsp;Zongyi Xie","doi":"10.1016/j.brainresbull.2026.111744","DOIUrl":"10.1016/j.brainresbull.2026.111744","url":null,"abstract":"<div><h3>Background</h3><div>White matter injury (WMI) is a key contributor to long-term cognitive deficits following intracerebral hemorrhage (ICH), yet its underlying mechanisms remain incompletely understood.</div></div><div><h3>Aims</h3><div>This study aims to investigate the role of histone H3K18 lactylation (H3K18la) and microglial function in post-ICH WMI and cognitive impairment.</div></div><div><h3>Methods</h3><div>Utilizing a collagenase-induced ICH mouse model, we assessed H3K18la expression dynamics (days 3, 7, 14, 21 post-ICH) and the effects of inhibiting lactate dehydrogenase (using Oxamate) or p300/CBP histone acetyltransferase (using A-485) on WMI and cognitive function. Furthermore, we employed PLX5622 (a colony-stimulating factor 1 receptor inhibitor) to deplete microglia (MG), alone or combined with A-485, to examine the role of p300/CBP inhibition in the context of MG absence. WMI was evaluated using myelin basic protein (MBP), neurofilament H (non-phosphorylated; SMI32) immunostaining, and transmission electron microscopy. Oligodendrocyte precursor cell (OPC) accumulation around the hematoma was quantified, and microglial depletion was verified by cell counting. Cognitive function was assessed up to 28 days post-ICH using the Morris Water Maze test.</div></div><div><h3>Results</h3><div>H3K18la levels were elevated and oligodendrocyte precursor cells (OPCs) increased in the perihematomal region post-ICH. A-485 administration significantly reduced microglial H3K18la, concomitantly suppressed OPC recruitment to the injury site, and exacerbated both WMI and long-term cognitive impairment. In contrast, oxamate administration did not significantly reduce microglial H3K18la or exacerbate cognitive deficits, but it did significantly aggravate WMI. PLX5622-induced MG depletion similarly aggravated WMI and cognitive deficits. However, combined PLX5622 and A-485 treatment did not produce additive worsening compared to MG depletion alone.</div></div><div><h3>Conclusion</h3><div>These results demonstrated that lactate-derived H3K18 lactylation (H3K18la), orchestrated by p300/CBP-mediated epigenetic reprogramming, serves as a critical endogenous neuroprotective axis of WMI following ICH. Microglia emerge as the cellular executors of this pathway. This lactate-p300/CBP-H3K18la axis thus represents a therapeutically targetable mechanism for enhancing post-hemorrhagic brain repair through microglia-guided myelin regeneration.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111744"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090182","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":"Exploring the mechanism by which puerarin inhibits neuroinflammation and alleviates lipopolysaccharide-induced anxiety-like behavior in mice via modulating gut microbiota based on the brain-gut axis theory","authors":"Ge Wang ,&nbsp;Qisheng Tang ,&nbsp;Dan Wang","doi":"10.1016/j.brainresbull.2025.111698","DOIUrl":"10.1016/j.brainresbull.2025.111698","url":null,"abstract":"<div><h3>Background</h3><div>The gut-brain axis (GBA) has been increasingly recognized as a potential contributor to anxiety pathophysiology. Puerarin possesses anti-inflammatory, antioxidant, and neuroprotective properties, but its anxiolytic mechanism via the GBA remains unclear. The intervention of puerarin on lipopolysaccharide (LPS)-induced anxiety-like behavior (ALB) in mice was investigated based on the GBA theory.</div></div><div><h3>Methods</h3><div>Forty mice were allocated at random: control, LPS, LPS+PueL (low-dose puerarin), and LPS+PueH (high-dose puerarin) groups (n = 10 each). ALB was evaluated by the elevated plus maze (EPM). Inflammatory cytokines were measured by ELISA. Tight junction proteins were detected by qPCR and Western blot. Gut microbiota (GM) was analyzed by 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>Compared with the Control, open arm entries (OAE) and open arm time (OAT) were decreased, inflammatory cytokine levels were elevated, intestinal tight junction protein expression was down-regulated, microbial diversity was reduced, and the abundance of pro-inflammatory bacterial genera was obviously increased in the LPS. In the LPS+PueH, OAE and OAT, inflammatory cytokine levels, tight junction protein expression, microbial diversity, and abundance of beneficial bacterial genera were evidently improved (<em>P</em> &lt; 0.05). Correlation analysis revealed that <em>Lactobacillus</em> and <em>Akkermansia</em> were positively correlated with OAE and OAT, whereas <em>Escherichia-Shigella</em> was negatively correlated (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Puerarin alleviated LPS-induced ALB in mice by suppressing neuroinflammation, restoring intestinal barrier integrity, and modulating GM balance, which was closely associated with GBA regulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111698"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803070","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":"Brain functional connectivity initiates structured reorganization at a critical oxygen threshold during hypoxia","authors":"Daehun Kang ,&nbsp;Koji Uchida ,&nbsp;Clifton R. Haider ,&nbsp;Norbert G. Campeau ,&nbsp;Myung-Ho In ,&nbsp;Erin M. Gray ,&nbsp;Joshua D. Trzasko ,&nbsp;Kirk M. Welker ,&nbsp;Matt A. Bernstein ,&nbsp;Max R. Trenerry ,&nbsp;David R. Holmes III ,&nbsp;Michael J. Joyner ,&nbsp;Timothy B. Curry ,&nbsp;John Huston III ,&nbsp;Yunhong Shu","doi":"10.1016/j.brainresbull.2026.111748","DOIUrl":"10.1016/j.brainresbull.2026.111748","url":null,"abstract":"<div><div>The human brain, one of the most energy-demanding organs, continuously adapts to internal and external challenges. Hypoxia, a reduction in oxygen availability, poses a substantial threat to brain function. Despite its importance, the nature of the brain’s adaptive response to hypoxia remains poorly understood. In this study, we investigated dynamic functional connectivity (FC) under acute hypoxic conditions (FiO₂ = 7.7 % and 11.8 %) in healthy adults using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and concurrent advanced physiological monitoring, including partial pressures of end-tidal oxygen (PetO₂) and carbon dioxide (PetCO₂) and peripheral oxygen saturation (SpO₂), and a Go/No-Go cognitive task to assess behavioral performance. Principal component analysis identified a hypoxia-responsive component in dynamic FCs across 400 cerebral parcels. This component captured hypoxia-specific FC changes that coincided with a critical drop in PetO₂ (∼53 mmHg), preceding subsequent changes in SpO₂, bulk BOLD signals, and behavioral performance. These FC changes were network-specific, with a marked increase primarily centered on the default mode network (DMN), which selectively synchronized with other high-level cognitive networks. In contrast, hypoxia-responsive connectivity showed limited involvement of visual networks, including connectivity with the DMN. These findings suggest that the brain engages in proactive and structured FC adaptations in anticipation of oxygen decline, rather than in response to it. FC-based metrics offer new insights into the temporal dynamics of brain resilience and may hold translational value for the early detection of vulnerability in neurological or neurodegenerative disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111748"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050399","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}