Brain Research Bulletin最新文献

{"title":"Characterization of the glymphatic system and early-phase β-amyloid imaging in Alzheimer's disease: A simultaneous PET/MR study","authors":"Yuying Jiao ,&nbsp;Wei Han ,&nbsp;Linhan Zhang ,&nbsp;Mengjiao Wang ,&nbsp;Zhehao Lyu ,&nbsp;Yexin Su ,&nbsp;Zeyu Wang ,&nbsp;Lifan Wang ,&nbsp;Jiafu Wang ,&nbsp;Peng Xu ,&nbsp;Yujie Hu ,&nbsp;Yang Yang ,&nbsp;Peng Fu","doi":"10.1016/j.brainresbull.2025.111368","DOIUrl":"10.1016/j.brainresbull.2025.111368","url":null,"abstract":"<div><div>Early-phase Aβ imaging can detect cerebral perfusion deficits, while glymphatic dysfunction is a key event in neurodegenerative diseases, including Alzheimer's disease (AD). However, their relationship within the AD continuum remains unclear. This study aimed to evaluate the role of the glymphatic system (diffusion tensor image analysis along the perivascular space, DTI-ALPS) and early-phase Aβ imaging in cognitive impairment using simultaneous PET/MR in healthy control (HC), Prodromal AD (PAD), and AD. It also examines the interaction between baseline amyloid (Aβ) burden and vascular burden in perfusion impairment and glymphatic dysfunction. AD patients showed lower SUVr of early-phase Aβ in the bilateral hippocampus, parahippocampal, and caudate (all P &lt; 0.05), indicating perfusion deficits in these regions. Compared to HC, a lower mean ALPS-index was found in the AD and PAD groups (P &lt; 0.001), suggesting that glymphatic dysfunction is an early event in AD. The mean ALPS-index was positively correlated with early-phase Aβ uptake in the bilateral hippocampus, parahippocampal, caudate, and thalamus (all P &lt; 0.001). Mediation analysis revealed that the ALPS-index plays a crucial mediating role between perfusion deficits and cognitive impairment. Baseline Aβ burden and early-phase Aβ perfusion deficits affected the ALPS-index with the mediation of vascular burden (PVS or WMH), while early-phase Aβ perfusion also directly influenced the ALPS-index. In conclusion, this study highlights the role of glymphatic dysfunction and cerebral perfusion deficits in the AD continuum, emphasizing their necessity as early pathological markers. These findings provide imaging evidence for early diagnosis and personalized management of AD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111368"},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913003","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-Derived Neurotrophic Factor Gene Polymorphism Differentially Affects Speech and Language Performance and Recovery after Stroke.","authors":"Firas Alfwaress, Karem H Alzoubi, Ahmed Alhusban","doi":"10.1016/j.brainresbull.2025.111367","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111367","url":null,"abstract":"<p><strong>Background: </strong>Stroke is the leading cause of long-term disability worldwide, with detrimental effects on many brain functions, such as speech and language. Data regarding the role of genetics in stroke recovery is lacking. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that was shown to be involved in stroke recovery. A single nucleotide polymorphism (SNP) in the BDNF gene was shown to affect its release and function. Data regarding the effect of this SNP on speech and language recovery after stroke is still lacking.</p><p><strong>Objective: </strong>This study assesses the role of BDNF gene polymorphism in speech and language performance and response to rehabilitation after stroke.</p><p><strong>Methods: </strong>patients with speech and language deficits referred to the speech and language rehabilitation clinic at King Abdullah University Hospital were recruited. A baseline speech and language assessment was performed, followed by a rehabilitation program. Additionally, a blood sample was obtained for BDNF genotyping.</p><p><strong>Results: </strong>Thirty-two patients participated in this study, with 12 patients (37.5%) having the metBDNF genotype. Patients with metBDNF genotype had significantly lower speech performance at baseline (23.3 Vs. 8.5; p=0.022) and lower response to the rehabilitation program (31.4 Vs. 39.1, p=0.032). Furthermore, the BDNF genotype was identified as an independent predictor of baseline speech performance. Language baseline performance and response to rehabilitation were not affected by the BDNF genotype.</p><p><strong>Conclusion: </strong>The results indicate a differential effect of BDNF genotype on speech performance and recovery after stroke.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111367"},"PeriodicalIF":3.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963596","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":"Activation of spinal PGC-1α regulates microglial polarization through a feedback loop between ROS-mediated mitochondrial dysfunction and the NLRP3 inflammasome in neuropathic pain.","authors":"Qingling Xu, Qiulin Zhu, Guoxu Ling, Tonghong Huang, Tingting Su, Yanhua Chen, Yubo Xie, Yu Zhong","doi":"10.1016/j.brainresbull.2025.111365","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111365","url":null,"abstract":"<p><strong>Background: </strong>An imbalance in microglial polarization plays an important role in the pathogenesis of neuropathic pain. PPARγ coactivator-1α (PGC-1α), a master coregulator of gene expression in mitochondrial biogenesis, is related to microglial polarization. However, the underlying mechanism involved is poorly understood.The aim of the present study was to explore the role of PGC-1α in regulating microglial polarization through a feedback loop between reactive oxygen species (ROS)-mediated mitochondrial dysfunction and the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of chronic constriction injury (CCI).</p><p><strong>Methods: </strong>we quantified pain behaviour after CCI; analysed the localization of PGC-1α and the changes in the expression of CD68 (an M1 microglial marker)/IBA1 and ARG1 (an M2 microglial marker)/IBA1 in the dorsal horn (DH) via immunofluorescence. Western blotting and immunofluorescence were used to examine the expression of target proteins. Quantitative real-time PCR (qPCR) was used to investigate the mitochondrial DNA copy number (mtDNA). ROS production was measured via dihydroethidium (DHE). SOD activity and the MDA content were measured via SOD and MDA assay kits, respectively. In addition, tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-10 levels were measured via enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The results revealed ROS-mediated mitochondrial dysfunction and NLRP3 inflammasome activation, microglia phenotype from the M2 to the M1 phenotype in the CCI rats.Interesting, ROS-mediated mitochondrial dysfunction is one of the critical mediators of NLRP3 inflammasome activation.NLRP3 inflammasome in turn cause ROS production and mitochondrial dysfunction, suggesting for the first time a feedback loop between ROS-mediated mitochondrial dysfunction and NLRP3 inflammasome in the neuropathic pain.The activation of PGC-1α shifts the microglial phenotype via the modulation of a feedback loop between ROS-mediated mitochondrial dysfunction and the NLRP3 inflammasome.</p><p><strong>Conclusions: </strong>These findings indicate that activation of PGC-1α could be a potential therapeutic approach to ameliorate neuropathic pain.</p>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111365"},"PeriodicalIF":3.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062106","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":"Corrigendum to \"Long noncoding RNA H19 prevents neurogenesis in ischemic stroke through p53/Notch1 pathway\" [Brain Res. Bull. 150 (2019) 111-117].","authors":"Jue Wang, Bin Cao, Haiping Zhao, Yan Gao, Yumin Luo, Yuhua Chen, Juan Feng","doi":"10.1016/j.brainresbull.2025.111362","DOIUrl":"https://doi.org/10.1016/j.brainresbull.2025.111362","url":null,"abstract":"","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":" ","pages":"111362"},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976988","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 interaction between metals and catecholamines: oxidative stress, DNA damage, and implications for human health","authors":"Elena Cassera ,&nbsp;Emanuele Ferrari ,&nbsp;Davide A.L. Vignati ,&nbsp;Andrea Capucciati","doi":"10.1016/j.brainresbull.2025.111366","DOIUrl":"10.1016/j.brainresbull.2025.111366","url":null,"abstract":"<div><div>The interaction between metals and catecholamines plays a pivotal role in the generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage. ROS are linked to several diseases, including neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. This review examines how essential metals (iron, copper, zinc, manganese) and a few non-essential metal(loid)s (mercury, chromium, arsenic, aluminum, cadmium, and nickel) contribute to oxidative stress in the presence of catecholamines. In the presence of metals, catecholamines can cause oxidative DNA modification, possibly resulting in cell apoptosis, by taking part in redox reactions and oxidizing to the corresponding aminochrome with simultaneous ROS production. Essential metals are vital for physiological functions, but imbalances in their homeostasis can be harmful. Furthermore, non-essential metals, commonly encountered through environmental or occupational exposure, can exhibit significant toxicity. Previous studies on catecholamine-induced oxidative stress focused on copper and iron, but this review emphasizes the need to investigate other neurotoxic metals and expand existing knowledge on the interactions between metals, catecholamines, and DNA damage. Results from such research could help prioritizing the development of new assessment methods associated with adverse outcome pathways, to reliably predict harmful effects on human health, aiding in the development of therapeutical strategies. The present work will help to shed light on the interplay of metals, catecholamines, and DNA damage in different diseases hopefully fostering new research in this still understudied topic. Future research should investigate the molecular mechanisms through which these metals affect neuronal health and contribute to disease pathogenesis.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111366"},"PeriodicalIF":3.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894473","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":"Mitigating morphine dependence and withdrawal: The role of venlafaxine and calcium channel blockers in mitochondrial damage and oxidative stress in the brain","authors":"Radman Amiri ,&nbsp;Faezeh Fallah ,&nbsp;Behnam Ghorbanzadeh ,&nbsp;Ali Akbar Oroojan ,&nbsp;Mohammad Amin Behmanesh ,&nbsp;Soheila Alboghobeish","doi":"10.1016/j.brainresbull.2025.111364","DOIUrl":"10.1016/j.brainresbull.2025.111364","url":null,"abstract":"<div><h3>Background</h3><div>The reasons for morphine dependence and withdrawal symptoms are oxidative stress and dysfunction of cell mitochondria in the brain. Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), mitigates oxidative stress, while calcium channel blockers (nimodipine/diltiazem) prevent Ca²⁺-mediated mitochondrial dysfunction. In the present study, the effects of simultaneous administration of venlafaxine and calcium channel blockers on dependence and withdrawal syndrome of morphine and the role of mitochondrial damage and oxidative stress were assessed.</div></div><div><h3>Methods</h3><div>In this experimental study, the analgesic effect of venlafaxine, nimodipine, and diltiazem was investigated using the hot plate test to determine the optimal doses of drugs to use in subsequent experiments. To induce morphine dependence and withdrawal syndrome, male NMRI mice were treated with 50 mg/kg S.C. morphine for three consecutive days and 5 mg/kg S.C. morphine on the fourth day. 2 hours after the last dose of morphine, naloxone (5 mg/kg) was injected intraperitoneally, and the signs of jumping and standing were evaluated for 0.5 hours. Venlafaxine (20 mg/kg) alone or in combination with nimodipine (10 mg/kg) and diltiazem (40 mg/kg) was administered half an hour before morphine 50 mg/kg for three days. Brain slides were stained and examined under a light microscope. Brain mitochondria were isolated using a repeated centrifugation method to investigate mitochondrial oxidative stress. The dehydrogenase activity (MTT), membrane potential (MMP), ROS production rate, glutathione (GSH), and malondialdehyde (MDA) contents of the brain mitochondria were measured. The data were expressed as mean±standard deviation, and a p-value less than 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>The administration of naloxone following repeated morphine injection increased withdrawal symptoms compared to the control group (morphine followed by solvent of naloxone) (P &lt; 0.01). Administration of venlafaxine-nimodipine and venlafaxine-diltiazem before morphine reduced these symptoms compared to the morphine + naloxone group (P &lt; 0.01). The injection of morphine followed by naloxone decreased MTT and GSH and increased MDA, MMP, and ROS compared to the control group (P &lt; 0.01), and the injection of venlafaxine-nimodipine and venlafaxine-diltiazem half an hour before morphine reduced these alterations when compared to morphine + naloxone group (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Coadministration of venlafaxine with calcium channel blockers could reduce morphine withdrawal symptoms and prevent its pathological damage. The suggested mechanism of this event is preventing mitochondrial damage and oxidative stress induced by morphine.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111364"},"PeriodicalIF":3.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913004","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":"Biological age prediction in schizophrenia using brain MRI, gut microbiome and blood data","authors":"Rui Han ,&nbsp;Wei Wang ,&nbsp;Jianhao Liao ,&nbsp;Runlin Peng ,&nbsp;Liqin Liang ,&nbsp;Wenhao Li ,&nbsp;Shixuan Feng ,&nbsp;Yuanyuan Huang ,&nbsp;Lam Mei Fong ,&nbsp;Jing Zhou ,&nbsp;Xiaobo Li ,&nbsp;Yuping Ning ,&nbsp;Fengchun Wu ,&nbsp;Kai Wu","doi":"10.1016/j.brainresbull.2025.111363","DOIUrl":"10.1016/j.brainresbull.2025.111363","url":null,"abstract":"<div><div>The study of biological age prediction using various biological data has been widely explored. However, single biological data may offer limited insights into the pathological process of aging and diseases. Here we evaluated the performance of machine learning models for biological age prediction by using the integrated features from multi-biological data of 140 healthy controls and 43 patients with schizophrenia, including brain MRI, gut microbiome, and blood data. Our results revealed that the models using multi-biological data achieved higher predictive accuracy than those using only brain MRI. Feature interpretability analysis of the optimal model elucidated that the substantial contributions of the frontal lobe, the temporal lobe and the fornix were effective for biological age prediction. Notably, patients with schizophrenia exhibited a pronounced increase in the predicted biological age gap (BAG) when compared to healthy controls. Moreover, the BAG in the SZ group was negatively and positively correlated with the MCCB and PANSS scores, respectively. These findings underscore the potential of BAG as a valuable biomarker for assessing cognitive decline and symptom severity of neuropsychiatric disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111363"},"PeriodicalIF":3.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942883","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":"BNSTGABA neurons regulate autophagy to alleviate depression with gastric dysfunction symptoms","authors":"Yi Yuan ,&nbsp;Jiangang Xu ,&nbsp;Shanlan Zhu ,&nbsp;Hongkun Ma ,&nbsp;Hao Wang ,&nbsp;Xiyang Wang ,&nbsp;Guoming Shen","doi":"10.1016/j.brainresbull.2025.111360","DOIUrl":"10.1016/j.brainresbull.2025.111360","url":null,"abstract":"<div><div>Gastric dysfunction is very common in depressed patients, and the coupling mechanism between the brain and the stomach is a key point in its occurrence. Electroacupuncture (EA) can act on both ‘form’ (i.e., the physical level) and ‘spirit’ (i.e., the mental-emotional level) in the treatment of negative emotions and gastrointestinal co-morbidities, realising the therapeutic effect of‘form-spirit co-medication’. The neurological mechanism is not clear.We developed a chronic unpredictable stress (CUMS) model, and gastric electrophysiological and behavioural results suggest that EA can alleviate depressive symptoms and improve gastric dysfunction accompanying depression. We found that the CUMS model inhibits GABAergic neurons in the bed nucleus of the stria terminalis (BNST), whereas BNST^GABA neurons are de-suppressed after EA intervention. Chemical activation of BNST^GABA neurons eliminated CUMS-induced depressive symptoms and gastric dysfunction with effects similar to EA treatment. In addition, transcriptomics data showed that excessive autophagy was present in the gastric tissues of CUMS model mice, which was alleviated by EA, and it was verified by Western Blot that EA may ameliorate depression-induced gastric dysfunction by modulating BNST^GABA neurons, which effectively inhibited excessive autophagy in the cells of gastric tissues. Thus, our study describes a neural mechanism that regulates autophagy in gastric cells via BNST^GABA neurons, thereby alleviating gastric dysfunction in depression, and provides a theoretical basis for electroacupuncture in the treatment of mood disorders with comorbid somatic symptoms.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111360"},"PeriodicalIF":3.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894474","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 janus face of astrocytes in multiple sclerosis: Balancing protection and pathology","authors":"Ahmad A. Abulaban ,&nbsp;Hayder M. Al-kuraishy ,&nbsp;Ali I. Al-Gareeb ,&nbsp;Ali K. Albuhadily ,&nbsp;Mustafa M. Shokr ,&nbsp;Athanasios Alexiou ,&nbsp;Marios Papadakis ,&nbsp;Gaber El-Saber Batiha","doi":"10.1016/j.brainresbull.2025.111356","DOIUrl":"10.1016/j.brainresbull.2025.111356","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neurodegeneration in the central nervous system (CNS), predominantly affecting young adults with a notable female predominance. While the pathogenesis of MS involves complex interactions between peripheral immune cells and CNS glia, astrocytes—the most abundant glial cells—play a dual role in disease progression. Traditionally classified into pro-inflammatory A1 and neuroprotective A2 phenotypes, recent single-cell and spatial transcriptomics reveal that human astrocytes exhibit a continuum of states beyond this binary paradigm. In MS, reactive astrocytes contribute to neurotoxicity by disrupting the blood-brain barrier (BBB), promoting glutamate excitotoxicity, and presenting antigens to autoreactive T cells. Conversely, they also support repair through neurotrophic factor release (e.g., BDNF, CNTF) and remyelination. Emerging therapies like dimethyl fumarate (DMF) and fingolimod modulate astrocyte reactivity, targeting oxidative stress and sphingosine-1-phosphate receptors to mitigate neuroinflammation. However, challenges persist in translating murine A1/A2 concepts to human MS, as human astrocytes display heterogeneous, context-dependent responses influenced by regional microenvironments and disease stages. Advanced techniques, including spatial multi-omics, highlight astrocyte-microglia crosstalk and metabolic reprogramming as key drivers of MS pathology. This review synthesizes current evidence on astrocyte heterogeneity, their Janus-faced roles in MS, and the therapeutic potential of astrocyte-targeted strategies, advocating for precision approaches that account for human-specific astrocyte biology. Future research must priorities human-centric biomarkers and dynamic modelling to bridge the gap between experimental findings and clinical applications.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111356"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894472","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":"Response of astrocytes and their interaction with surrounding brain cells after acute ischemia-reperfusion analyzed by single-cell transcriptome sequencing","authors":"YongHong Wu ,&nbsp;Lei Xie ,&nbsp;Jing Sun ,&nbsp;Qing Wang ,&nbsp;WangXiao Xia ,&nbsp;Qiang Cai ,&nbsp;XiaoYun Lu ,&nbsp;XingChun Gou","doi":"10.1016/j.brainresbull.2025.111355","DOIUrl":"10.1016/j.brainresbull.2025.111355","url":null,"abstract":"<div><div>Astrocytes play a key role in the occurrence and development of ischemic stroke. However, reactive astrocytes have both detrimental and protective roles in ischemic stroke. Regrettably, the stimulation signals associated with the transformation of astrocytes into different subclusters lack systemic analysis, and the mechanism by which astrocytes produce multiple effects is not entirely clear. We investigated the heterogeneity of mouse astrocytes 12 h after cerebral ischemia-reperfusion via Single-cell RNA sequencing and verified gene expressions by reverse transcription-polymerase chain reaction. We acquired astrocyte subclusters’ transcriptional characteristics involved in diversified functions. To explore what stimulus signals cause astrocyte heterogeneity, we present a blueprint for cellular communication between astrocyte subclusters and other surrounding brain cells 12 h after ischemia-reperfusion, and identified 9 genes which are potential and promising for being therapeutic targets and 6 genes were specific to astrocyte subcluster 2 that tend to resist ischemia-reperfusion injury. At 12 h after ischemia-reperfusion, each subcluster of astrocytes is characteristic in terms of function and communication with surrounding cells, which is based on the activation genes and transcription molecules that we have revealed with subcluster characteristics. Our results provide a basis for revealing the anti-injury response of astrocytes to cerebral ischemia-reperfusion, which involves coordination of different subclusters and the coordination of astrocytes with surrounding brain cells.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"226 ","pages":"Article 111355"},"PeriodicalIF":3.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881405","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}