Behavioural Brain Research最新文献

{"title":"Postural and cardiorespiratory responses to emotionally-laden whole-body expressions","authors":"Mariana Rodrigues Alves ,&nbsp;Anaelli Aparecida Nogueira-Campos ,&nbsp;Adriana Ribeiro de Macedo ,&nbsp;Angela Nogueira Neves ,&nbsp;Talita P. Pinto ,&nbsp;Fabio Vieira dos Anjos ,&nbsp;Claudia Domingues Vargas ,&nbsp;Luis Aureliano Imbiriba","doi":"10.1016/j.bbr.2026.116049","DOIUrl":"10.1016/j.bbr.2026.116049","url":null,"abstract":"<div><div>Postural and autonomic adjustments are commonly described during the observation of emotional stimuli. Thus, this study investigated the physiological impact of emotional images viewing revealed by whole-body expressions. Body sway and cardiorespiratory signals were recorded in thirty-nine healthy young people who maintained an upright stance while observing 20 neutral, 20 happiness (positive) or 20 anger (negative) images from the Bodily Expressive Action Stimulus Test (BEAST) database. Participants rated each image considering their valence and arousal dimensions with the Self-Assessment Manikin. Additionally, emotional recognition level was rated using a three alternative-forced-choice task (happiness, anger, and neutral). A repeated-measures one-way analysis of variance (ANOVA) was used to compare the main physiological variables among emotionally-laden blocks. Valence statistically differed among blocks. The emotional recognition rate was above 70 % for all blocks. There was a significant decrease in body sway area during the observation of anger whole-body expressions compared to the neutral and happiness ones. The mean power frequency in the medial-lateral axis showed a significant increase during viewing anger images compared to the neutral one. Further, there was a significant increase in the heart rate variability during observation of anger whole-body expressions compared to the happiness one. These findings revealed physiological adjustments in the observer while viewing whole-body expressions consistent with the emotional processing experience. Therefore, the observation of images depicting anger whole-body expressions led to postural and autonomic changes in agreement with defensive responses (”postural immobility”).</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"503 ","pages":"Article 116049"},"PeriodicalIF":2.3,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture alleviates depression-like behavior after spinal cord injury via SIRT1/HMGB1 signaling axis mediated ferroptosis","authors":"Wu Zhou ,&nbsp;Bo Hei ,&nbsp;Zhixin Liu ,&nbsp;Shuai Chen ,&nbsp;Yifei Fan ,&nbsp;Haifeng Zhang ,&nbsp;Bingkai Ren ,&nbsp;Yong Fu ,&nbsp;Jiacong Tan","doi":"10.1016/j.bbr.2026.116052","DOIUrl":"10.1016/j.bbr.2026.116052","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Spinal cord injury (SCI) induces neuroinflammation and brain alterations that contribute to depression-like behaviors. Ferroptosis plays a critical role in neuronal injury following SCI. HMGB1 regulates ferroptosis, while SIRT1 inhibits HMGB1 activity. Electroacupuncture (EA) has demonstrated neuroprotective and antidepressant effects, but its mechanisms in SCI remain unclear. This study investigated whether EA alleviates post-SCI depression by activating SIRT1, retaining HMGB1 in the nucleus, and limiting ferroptosis in the prefrontal cortex (PFC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A moderate SCI model was established in male Sprague-Dawley rats to assess the neuroprotective effects of EA. Behavioral assessments for depression, histopathological analysis of cortical neurons, and quantification of ferroptosis biomarkers—including malondialdehyde (MDA), Fe&lt;sup&gt;2 +&lt;/sup&gt; , glutathione (GSH), and mitochondrial integrity—were conducted. Western blotting and immunofluorescence staining were used to analyze protein expression levels of SIRT1, HMGB1, acetylated HMGB1 (Ace-HMGB1), GPX4, and other oxidative stress markers. To assess the role of SIRT1 activation in mediating EA's effects, the SIRT1 inhibitor EX-527 was co-administered with EA. Additionally, HMGB1 overexpression (OE-HMGB1) and pharmacological inhibition with glycyrrhizic acid (GA) were employed to validate the specificity of the SIRT1/HMGB1 pathway in EA’s neuroprotective action.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;EA significantly improved depression-like behaviors in SCI rats, as evidenced by increased sucrose preference, reduced immobility, and enhanced social interaction. EA also mitigated neuronal damage, preserved mitochondrial structure, and alleviated oxidative stress by reducing ROS and Fe&lt;sup&gt;2+&lt;/sup&gt; levels while increasing GPX4 and GSH expression. Western blot and immunofluorescence analysis showed that EA activated SIRT1 and inhibited HMGB1 translocation to the cytoplasm, reducing HMGB1 acetylation. HMGB1 overexpression (OE-HMGB1) reversed these protective effects, promoting HMGB1 translocation and acetylation. Furthermore, co-treatment with EX-527 (SIRT1 inhibitor) and GA (HMGB1 inhibitor) diminished EA’s neuroprotective effects, confirming the pivotal roles of SIRT1 activation and HMGB1 modulation in EA’s neuroprotection and improvement of depression-like behaviors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;These findings demonstrate that EA protects against SCI-induced depression by inhibiting ferroptosis through activation of the SIRT1/HMGB1 signaling axis. This study unveils a novel mechanism underlying EA's neuroprotective effects in SCI-related depression and highlights ferroptosis modulation as a potential therapeutic strategy. By integrating traditional Chinese medicine with modern molecular pathophysiology, this work offers new insights into EA's mechanisms in treating SCI-induced depression and proposes a promising avenue for future the","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"503 ","pages":"Article 116052"},"PeriodicalIF":2.3,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploration of the association between sub bands of gamma and individual symptoms of melancholia","authors":"Christopher F. Sharpley,&nbsp;Ian D. Evans,&nbsp;Vicki Bitsika,&nbsp;G.Lorenzo Odierna","doi":"10.1016/j.bbr.2026.116060","DOIUrl":"10.1016/j.bbr.2026.116060","url":null,"abstract":"<div><div>Melancholia is often found to be unresponsive to standard antidepression medication. In the search for biomarkers that may also suggest possible treatment options, some attention has been given to EEG data. However, this research has largely ignored the gamma band of electrical activity in the brain (30–130 Hz). In an exploratory investigation of the association between melancholia and gamma wave activity, a standardized 8-item scale was completed by 100 community participants, who also underwent eyes-open and eyes-closed EEG data collection from 30 brain sites. There was a significant association between severity of depression, melancholia, and gamma. Individual melancholia symptoms were found to have meaningful correlations with specific EEG sites, which were then further explored via source localization (<em>eLORETA</em>). Most associations between gamma and melancholia items as measured via <em>eLORETA</em> were direct, indicating that, as gamma increased, so did participants’ severity of particular melancholia symptoms, implying that depressed participants utilized increased neurocognitive activity as a possible strategy for coping with aspects of melancholia. Although these results are exploratory, they address a gap in the literature and suggest several hypotheses for future research.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"503 ","pages":"Article 116060"},"PeriodicalIF":2.3,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of vitamins and gut microbiota in neurodevelopmental disorders","authors":"Lizhi Liu ,&nbsp;Zhuoliang Gu ,&nbsp;Boyu Guo ,&nbsp;Yanan Wang ,&nbsp;Tatiana V. Kirichenko ,&nbsp;Yuliya V. Markina ,&nbsp;Alexander M. Markin ,&nbsp;Huiming Hua ,&nbsp;Dahong Li ,&nbsp;Anthony Yiu-Ho Woo","doi":"10.1016/j.bbr.2026.116028","DOIUrl":"10.1016/j.bbr.2026.116028","url":null,"abstract":"<div><div>Good nutritional status in early life is vital for neurodevelopment, but eating disorders like picky eating heighten risks of nutritional imbalance and dysbiosis. Dysregulated gut microbiomes are increasingly linked to gastrointestinal issues and neurodevelopmental disorders. Vitamin deficiency may aggravate these conditions, emphasizing the need for focused nutritional care. The gut microbiota plays a key role in brain function and development, offering potential as a therapeutic target. At present, supplementation of probiotics, prebiotics, vitamins and other nutrients is presumed to produce some benefits to neurodevelopmental disorders though robust data on their effectiveness remain scarce. We propose that vitamin deficiency and dysbiosis interact, influencing neurodevelopment and brain function. Our review identifies key substrates such as vitamins, short-chain fatty acids, cytokines, neurotransmitters, and tryptophan metabolites in this network and provides mechanistic insights into their roles in the pathogenesis of neurodevelopmental disorders, paving the way for personalized strategies to address these conditions.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116028"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex and estrous phase influence functional connectivity during fear extinction","authors":"Alyssa A. Hohorst ,&nbsp;Jessica D. Westerman ,&nbsp;Carolina Sanchez-Mendoza ,&nbsp;Margaret K. Tanner ,&nbsp;Miles Q. Dryden ,&nbsp;Juliet R. Freund ,&nbsp;Remla A. Abdul ,&nbsp;Kevin M. Crombie ,&nbsp;Benjamin N. Greenwood","doi":"10.1016/j.bbr.2026.116039","DOIUrl":"10.1016/j.bbr.2026.116039","url":null,"abstract":"<div><div>Female rats exposed to fear extinction during the proestrus and estrus phases (Pro/Est) or following estradiol administration in ovariectomized females show enhanced extinction memory and reduced fear relapse relative to males and females extinguished during the metestrus and diestrus phases (Met/Di). In Pro/Est females, this effect requires activity of the substantia nigra-to-dorsolateral striatum (SN-DLS) dopamine (DA) pathway during extinction. Although elevated ovarian hormones can enhance SN-DLS DA activity, it remains unclear whether estrous phase also influences activity of catecholaminergic neurons in regions beyond the SN during extinction. Furthermore, how the nigrostriatal pathway interacts with traditional extinction networks during extinction has not yet been investigated. To address these questions, we examined sex- and estrous phase-dependent differences in neural activation and functional connectivity during extinction across a distributed network including midbrain catecholaminergic regions, traditional fear extinction networks, and striatal subregions. During extinction, Pro/Est females froze less than males and Met/Di females, exhibited less cFos in the prelimbic cortex and cingulate gyrus compared to males, had greater cFos in the medial amygdala relative to males, and displayed greater cFos within ventral tegmental area DA neurons compared to males and Met/Di females. Furthermore, functional connectivity during extinction was highest in Pro/Est females, with the DLS identified as a hub, indicating high influence over network connectivity. These findings provide new insight into how sex and estrous phase influence extinction processing and suggest the DLS may be a key region influencing extinction learning in Pro/Est females.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116039"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: “Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors” [Behav. Brain Res. 396 (2021) 112906]","authors":"Yun-Fang Jia ,&nbsp;Katheryn Wininger ,&nbsp;Lee Peyton ,&nbsp;Ada Man-Choi Ho ,&nbsp;Doo-Sup Choi","doi":"10.1016/j.bbr.2026.116053","DOIUrl":"10.1016/j.bbr.2026.116053","url":null,"abstract":"","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116053"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regular exercise ameliorates cognitive function in APOE-/- mice via the VEGF/ERK signaling pathway","authors":"Zhiyuan Wang ,&nbsp;Qiming Yang ,&nbsp;Xiangli Tong ,&nbsp;Meiqing Liao ,&nbsp;Zelin Hu ,&nbsp;Shaoze Huang ,&nbsp;Peng Wang ,&nbsp;Zhen Tong ,&nbsp;Yishan Chen ,&nbsp;Yirong Wang ,&nbsp;Wenfeng Liu","doi":"10.1016/j.bbr.2025.116005","DOIUrl":"10.1016/j.bbr.2025.116005","url":null,"abstract":"<div><div>Impaired synaptic plasticity underlies cognitive impairment as a core pathological substrate. While aerobic exercise represents a significant non-pharmacological intervention for enhancing synaptic plasticity, its precise molecular mechanisms remain incompletely defined. This study investigated whether aerobic exercise ameliorates synaptic plasticity and synaptic loss in Apolipoprotein E homozygous knockout (APOE^-/-) mice by modulating the Vascular Endothelial Growth Factor (VEGF)/Extracellular Signal-Regulated Kinase (ERK) signaling pathway to mitigate cognitive function. Eight-week-old male wild-type C57BL/6 J mice served as controls, while APOE^-/- mice were randomly allocated to sedentary or exercise groups. The exercise group underwent a 12-week moderate-intensity treadmill training protocol. Following spatial learning and memory assessment via the Morris water maze (MWM) testing, analyses included HE staining, Nissl staining, Oil red O staining, Golgi staining, ELISA, Immunofluorescence, Western blot, and RNA sequencing (RNA-Seq). Results demonstrated that aerobic exercise improved spatial learning and memory impairments, attenuated cerebral amyloid-beta (Aβ) deposition, increased hippocampal and prefrontal cortical dendritic spine density, and upregulated key synaptic proteins. Subsequent RNA-Seq analysis and validation revealed the underlying mechanism: aerobic exercise activated the VEGF/ERK pathway, which in turn reduced dendritic spine loss, increased synaptic protein expression, and enhanced synaptic structural remodeling, ultimately improving cognitive function. These findings provide a novel mechanistic foundation for cognitive impairment interventions and identify promising therapeutic targets.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116005"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiaochaihu decoction alleviates chronic stress-induced depressive-like behavior in mice by modulating the gut microbiota-brain axis","authors":"Xiangwei Zhao ,&nbsp;Jing Liang ,&nbsp;Ting Zhou ,&nbsp;Jun Hou ,&nbsp;Jingzi Yu ,&nbsp;Jinfu Shi ,&nbsp;Jun Du ,&nbsp;Haitao Wang ,&nbsp;Xiujun Zhang ,&nbsp;Xueliang Shang","doi":"10.1016/j.bbr.2026.116046","DOIUrl":"10.1016/j.bbr.2026.116046","url":null,"abstract":"<div><h3>Background</h3><div>Xiaochaihu Decoction (XCHD) has shown potential in treating neurological disorders, but its mechanisms in alleviating depression remain unclear.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to examine if the XCHD was able to alleviate depressive-like impairment in a mouse model of chronic mild stress.</div></div><div><h3>Materials and methods</h3><div>Fifty male C57BL/6 mice were divided into five groups: control (CON), stress (CUMS), stress with low and high XCHD doses (CUMS+<span>L</span>-XCHD, CUMS+H-XCHD), and fluoxetine (CUMS+FLX). The deprssion model was established using chronic unpredictable mild stress (CUMS) and isolated feeding. Animal behavior was assessed using the sucrose preference and open-field tests. Neuroplasticity, inflammation, and gut microbiota were analyzed using Western blotting, immunofluorescence, and 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>XCHD increased sucrose consumption and improved spatial learning and memory in stressed mice. It also alleviated anxiety and behavioral despair, restored hippocampal neuroplasticity, and reduced inflammation. XCHD modulated the Nogo-A/S1P2R-Gαq-PKC signaling pathway and enhanced tight junction proteins in the colon. Additionally, XCHD restored gut microbiota balance, increasing <em>Firmicutes</em> and reducing <em>Bacteroides</em> and <em>Proteobacteria</em>.</div></div><div><h3>Conclusion</h3><div>XCHD ameliorates depressive-like symptoms by modulating the gut microbiota-brain axis, enhancing neuroplasticity, and reducing inflammation, suggesting its potential as an antidepressant therapy.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116046"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing-dependent immune modulation of learning in a long-interval rodent model of anticipatory nausea","authors":"Indra R. Bishnoi ,&nbsp;Vangel M. Matic ,&nbsp;Lily Wang ,&nbsp;Caitlin T. Ravichandran ,&nbsp;Grace Lake ,&nbsp;Martin Kavaliers ,&nbsp;Klaus-Peter Ossenkopp","doi":"10.1016/j.bbr.2026.116026","DOIUrl":"10.1016/j.bbr.2026.116026","url":null,"abstract":"<div><div>Anticipatory nausea is a classically conditioned response to cues that have been associated with a nauseating stimulus. In rodents, anticipatory nausea can be modelled by pairing the novel cue of a distinct context with the toxic effects of lithium chloride (LiCl), which leads to anticipatory nausea responses (e.g. gaping) when exposed to the context alone. Previous work has shown that lipopolysaccharide (LPS) attenuates LiCl-induced anticipatory nausea. However, these studies use short inter-trial intervals (ITIs), which limits our understanding of how LPS attenuates LiCl-induced anticipatory nausea (e.g., through associative or non-associative mechanisms). We developed a long interval (7-day ITI) rodent model to enhance the translational relevance of anticipatory nausea research and to begin understanding the mechanisms underlying LPS effects. Adult male Long Evans rats were administered LiCl (127 mg/kg) or vehicle control (NaCl) intraperitoneally (i.p.) paired with a 30 min exposure to a distinct context for 4 conditioning trials at 7-day intervals. Rats were administered either LPS or NaCl (200 μg/kg, i.p.) immediately after the conditioning trials (post-conditioning) or LPS 90 mins prior to the conditioning trials (pre-conditioning). These trials were followed by 4 drug-free test/extinction trials. LiCl induced significant conditioned gaping responses with long ITIs. Pre-conditioning LPS robustly attenuated conditioned gaping. For post-conditioning LPS, we did not detect an attenuation using the long interval model. The use of long ITIs enabled the assessment of the temporally dependent effects of LPS on anticipatory nausea. These findings advance current models of anticipatory nausea and highlight new directions for investigating the immune modulation of nausea-related behaviours.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116026"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLB regulates microglial M1/M2 polarization after cerebral ischemic injury via the TLR4 signaling pathway","authors":"Guanghong Shen ,&nbsp;Jianbo Xu ,&nbsp;Jiansong Chen ,&nbsp;Irum Naz Abbasi ,&nbsp;Xia Yuan ,&nbsp;Fei Wu ,&nbsp;Javaria Sundus ,&nbsp;Qining Yang ,&nbsp;Marong Fang ,&nbsp;Nashwa Amin","doi":"10.1016/j.bbr.2026.116038","DOIUrl":"10.1016/j.bbr.2026.116038","url":null,"abstract":"<div><div>Inflammatory injury after ischemic stroke (IS) severely limits the treatment of stroke. Microglial polarization involved in the regulation of neuroinflammatory responses and brain injury related to IS. Glibenclamide (GLB) has been proven to inhibit microglial activation and alleviate neuroinflammation. However, the effect of GLB on microglial polarization and its mechanism remain unclear in IS. Here, we study the neuroprotective effect of GLB and its possible mechanism. In this study, the area of infarction, blood-brain barrier (BBB) permeability, and zea longa score of the mice were detected. Neurobehavioral functions were evaluated using the Rota-Rod and Open Field Test (OFT). Western blotting was performed to assess the protein levels of Sur1, Trpm4, TLR4, NF-κB, IL-1β, and TGF-β, while immunofluorescence (IF) was used to detect Iba-1, iNOS, and Arg-1. Our results demonstrated that GLB-mediated inhibition of the Sur1-Trpm4 channel reduced infarct size, preserved BBB integrity, and improved neurological function. GLB upregulated TGF-β and Arg-1 expression while downregulating TLR4, NF-κB, IL-1β, Iba-1, and iNOS in IS mice. It exerted neuroprotective effects and alleviated neuroinflammation. In summary, GLB may mitigate IS by modulating microglial M1/M2 polarization and suppressing TLR4/NF-κB pathway activation.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":"502 ","pages":"Article 116038"},"PeriodicalIF":2.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}