Molecular Neurobiology最新文献

{"title":"Mbnl1 Protects Against Cerebral Ischemia-Reperfusion Injury by Modulating Microglia/Macrophage Polarization via NF-κB Pathway.","authors":"Wenting Xu, Mengjia Zhou, Linlin Li, Yuqing Zhang, Tianya Zhang, Xiangjian Zhang","doi":"10.1007/s12035-025-05180-1","DOIUrl":"10.1007/s12035-025-05180-1","url":null,"abstract":"<p><p>Activated and polarized microglia regulate neuroinflammatory responses and programmed cell death processes in ischemic stroke. Although the inactivation of muscleblind-like 1 (Mbnl1) is known to cause structural defects in the brain, its role in microglial apoptosis and polarization remains unclear. This study aims to explore the mechanism of Mbnl1 in ischemic stroke, particularly its role in the regulation of microglial apoptosis and polarization, as well as its impact on neuroinflammatory responses and cognitive dysfunction. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. Mbnl1 overexpression exerts a protective effect against ischemic stroke by regulating microglia-mediated neuroinflammation through inhibition of the NF-κB signaling pathway. This modulation promotes cognitive recovery in C57BL/6N mice with stroke, highlighting Mbnl1 as a potential therapeutic target for stroke treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13899-13916"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Link Between IL-6 rs1800795 G > C SNP and the Severity of Epstein-Barr Virus-Associated Multiple Sclerosis: Potential Impact on Cognitive Impairment.","authors":"Tokka M Hassan, Azza M El Amir, Nahla Elsayed Nagy, Nashwa El-Khazragy","doi":"10.1007/s12035-025-05211-x","DOIUrl":"10.1007/s12035-025-05211-x","url":null,"abstract":"<p><p>Multiple Sclerosis (MS) is a chronic immune-mediated neurological disorder frequently accompanied by cognitive impairment, which affects up to 60% of patients and is associated with faster disease progression and greater disability. Interleukin-6 (IL-6), a key proinflammatory cytokine involved in neuroinflammation, has been implicated in MS pathogenesis, and the rs1800795 (-174 G>C) single nucleotide polymorphism (SNP) in the IL6 gene may influence disease susceptibility and clinical severity. This study investigated the association between the IL6 rs1800795 polymorphism and clinical outcomes in Epstein-Barr virus (EBV)-positive MS patients, with a particular focus on cognitive dysfunction. A case-control design was employed, including 300 participants: 150 EBV-positive MS patients and 150 matched healthy controls. Genotyping was performed using TaqMan-based PCR, and clinical data such as disability status, disease progression, and cognitive performance were analyzed. The CC genotype was significantly more frequent in MS patients and was associated with a higher risk of severe disability (OR = 6.11, p = 0.0004), faster disease progression, and increased likelihood of cognitive impairment. These findings suggest that the IL6 rs1800795 polymorphism, particularly the CC genotype, contributes to MS susceptibility and adverse clinical outcomes. IL6 genotyping may hold promise as a predictive tool for disease progression and cognitive decline in EBV-associated MS, offering insights for more personalized therapeutic strategies.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14089-14100"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Fatty Acid Binding Protein 7 in Neurological Diseases.","authors":"Yingxi Chen, Jiarui Liu, Yurou He, Yang Lü, Weihua Yu","doi":"10.1007/s12035-025-05071-5","DOIUrl":"10.1007/s12035-025-05071-5","url":null,"abstract":"<p><p>Fatty acid binding protein 7 (FABP7) is a pivotal cytoplasmic protein involved in the transport and metabolism of fatty acids, with critical functions in the nervous system. This review highlights recent advances in understanding the role and mechanisms of FABP7 in neurological diseases. It begins with an overview of FABP7's distribution and expression in the nervous system, emphasizing its involvement in essential biological processes such as lipid metabolism, energy regulation, synaptic transmission, cell growth, and neuroinflammation. This review also explores FABP7's associations with major neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), schizophrenia, and depression, shedding light on its dual roles in neuroprotection and neurodegeneration. These findings position FABP7 as a promising target for novel therapeutic strategies. By unraveling its precise mechanisms and contributions to both neural health and disease, future research on FABP7 has the potential to revolutionize treatments for neurological disorders, offering innovative directions for therapeutic development.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14801-14810"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Connection Between BDNF/TrkB and AC/cAMP/PKA/CREB Signaling Pathways: Potential for Neuroprotection and Therapeutic Targets for Neurological Disorders.","authors":"Abhishek Kumar Gupta, Sumedha Gupta, Sidharth Mehan, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula","doi":"10.1007/s12035-025-05001-5","DOIUrl":"10.1007/s12035-025-05001-5","url":null,"abstract":"<p><p>The BDNF/TrkB and AC/cAMP/PKA/CREB signaling pathways play a vital role in neuroplasticity, neuronal survival, and cognitive functions. This review explores its physiological and pathological implications in neurological disorders, with a focus on neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs). Neurological conditions increasingly burden public health, making understanding the biochemical mechanisms that underpin these diseases critical. BDNF, a neurotrophic factor, binds to the TrkB receptor, activating multiple intracellular signaling cascades that regulate cellular responses essential for neurogenesis, memory, and learning. Dysregulation within this pathway has been linked to various NDDs, as well as NPDs. Key components of the path, including adenylyl cyclase and cyclic AMP, mediate the effects of neurotransmitters and growth factors, influencing downstream targets like PKA and CREB, which are crucial for gene expression and synaptic changes. Furthermore, the review discusses the challenges of targeting this pathway for therapeutic interventions, including receptor isoform diversity, blood-brain barrier penetration, and potential side effects. Future strategies may include the development of selective TrkB modulators, nanoparticle carriers for drug delivery, and innovative gene therapy techniques. Advancing the understanding of this complex signaling network holds promise for effective interventions in treating neurological and psychiatric disorders, ultimately enhancing neuroprotection and cognitive resilience.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14627-14659"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"17β-Trenbolone Increases the Release of Lipocalin 2 via the Brain-Liver Axis and Causes Alzheimer's Disease-Like Symptoms in CSDS-Induced Mice.","authors":"Xiang Zuo, Xiaochen Kuang, Yudi Zhao, Jingyi Tuo, Huijuan Bai, Qili Zhao, Xin Zhao, Xizeng Feng","doi":"10.1007/s12035-025-05186-9","DOIUrl":"10.1007/s12035-025-05186-9","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate the neurological and behavioural effects of exposure to the environmental endocrine disruptor 17β-trenbolone (17-TB) exposure in chronic social defeat stress (CSDS)-induced mice and elucidate the role of lipocalin 2 (LCN2) in linking peripheral inflammation to neurodegeneration.</p><p><strong>Methods and materials: </strong>Male BALB/c mice were subjected to the CSDS paradigm and treated with 17-TB (100 μg/kg) or vehicle control for 10 consecutive days. Behavioural assessments, including novel object recognition test, novel object location test and social interaction test, were conducted to evaluate cognitive memory and social behaviour. Western blotting, ELISA and immunofluorescence were used to analyse LCN2 expression and related inflammatory markers in the liver and brain.</p><p><strong>Results: </strong>The results showed that 17-TB exposure exacerbated the induction of serum TNF-α and IL-1β inflammation in CSDS-induced mice, leading to activation of the hepatic IL-6 inflammatory factor pathway. This enhanced the release of hepatic LCN2 and stimulated its expression in the medial prefrontal cortex (mPFC) via the peripheral circulation, which subsequently activated the dorsal motor vagal nucleus (DMX) through cholinergic neuron (ChAT⁺) hyperactivation and c-Fos⁺ upregulation. This neurovisceral circuit ultimately induces hippocampal and cortical amyloid-β (Aβ) deposition, leading to cognitive memory and social deficits, thereby inducing Alzheimer's disease (AD)-like pathological changes.</p><p><strong>Conclusion: </strong>This study highlights the critical role of the brain-liver axis in inducing LCN2 release and ultimately cognitive deficits similar to AD-like symptoms in a 17-TB-exposed CSDS-induced mouse model, highlighting the risk of environmental endocrine disruptors causing neurodegenerative diseases that require further investigations and safety assessments.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"13958-13974"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Predictive Value of Oxylipins for Cognitive Measures and White Matter Hyperintensities in Alzheimer's Disease Continuum Compared to Conventional Beta‑amyloid and Tau Protein Biomarkers.","authors":"Alireza Shaabanpoor Haghighi, Mahsa Mayeli, Elham Ramezannezhad, Negin Pouroushaninia, Rezvan Barzegar Parizi, Mahtab Nourollahi-Foumeshi, Nasim Idelkhani, Zahra Dadjou, Niloofar Saeedipour, Negar Safaee, Homa Partoandaz, Mahan Shafie, Mohammad Sadeghi, Marjan Falahati","doi":"10.1007/s12035-025-05185-w","DOIUrl":"10.1007/s12035-025-05185-w","url":null,"abstract":"<p><p>Oxylipins are signaling molecules that result from the oxidation of long-chain polyunsaturated fatty acids, and they have been attracting attention due to their potential use as biomarkers for the early detection of Alzheimer's disease (AD) and other disorders. In contrast to beta-amyloid and tau protein biomarkers, we aimed to investigate the potential of oxylipins as an AD biomarker to predict cognitive measures. This study analyzed data from 703 participants (mean age 60 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We included 150 cognitively normal (CN) participants, 240 patients with early mild cognitive impairment (EMCI), 145 with late mild cognitive impairment (LMCI), 59 with subjetive memory complaints (SMC), and 109 with AD. Cognitive assessments were conducted using the clinical dementia rating scale (CDR), and cerebrospinal fluid (CSF) biomarkers (Aβ1-42 and p-tau181) were measured via the Luminex platform. Metabolite associations with CSF biomarkers were evaluated using random forest regression and linear regression models, with adjustments for age and sex and normalization for total intracranial volume (tICV). In the random forest regression model, Aβ42 was the most significant predictor for EMCI, while BSH_Sphingosine1P18.2 and BSL_GCDCA were significant for LMCI and MCI, respectively. Aβ42 appeared in SMC and CN but with lower significance than in EMCI. In CN, ASL_ResolvinE2 was most important. BSL_12_HETE was the strongest predictor for AD (R-squared = 0.199, metabolite-CSF R-squared = 0.024). Additionally, BSH_FA20.4_w6 (R-squared = 0.1772) outperformed CSF metabolites in EMCI detection, and BSH_Sphingosine1P16.1 (R-squared = 0.19) outperformed CSF metabolites in LMCI detection. Our findings suggest that select oxylipins may serve as predictive biomarkers of cognitive performance, although conventional CSF biomarkers remain superior for predicting the cognitive findings in the early stages.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14156-14166"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alexander's Disease: Potential Drug Targets and Future Directions.","authors":"Emily Zavala, Tahl Zimmerman","doi":"10.1007/s12035-025-05083-1","DOIUrl":"10.1007/s12035-025-05083-1","url":null,"abstract":"<p><p>Alexander's disease is a rare neurodegenerative disorder primarily characterized by upregulation of the GFAP gene and the formation of Rosenthal fibers. Its prognosis is fatal, with limited treatment options currently available. The GFAP protein is a marker for mature astrocytes. It results in the upregulation of reactive astroglioses. Reactive astroglioses is a neuroprotective condition that, when functioning correctly, helps protect the brain from stress and injury and prevents further injury. However, unregulated reactive astroglioses is linked with many neurodegenerative diseases. Due to the relative rarity in the incidence of AxD, treatment options have not been as widely investigated. This review explores potential drug targets that may impact GFAP gene expression, such as STAT3, GDNF, NF-kB, LCN-2, and the LPS pathway. These drug targets have previously been or are currently being explored in other neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The only treatment option currently in clinical trial phases involves methods to induce the knockout of the GFAP gene. Due to GFAP's neuroprotective role in brain injury and stress, it is important to explore alternative treatment options that downregulate GFAP as opposed to shutting it off entirely.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"15010-15023"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Availability of Essential Amino Acids Disrupts Differentiation of Anorexigenic POMC Neurons in the Fetal Rat Hypothalamus.","authors":"Pieter Vancamp, Isabelle Grit, Marie Demonceaux, Véronique Ferchaud-Roucher, Patricia Parnet, Valérie Amarger","doi":"10.1007/s12035-025-05201-z","DOIUrl":"10.1007/s12035-025-05201-z","url":null,"abstract":"<p><p>Intrauterine growth restriction (IUGR) is associated with an elevated risk of long-term metabolic disorders, including obesity and type 2 diabetes, aligning with the Developmental Origins of Health and Disease hypothesis. However, the mechanisms underlying metabolic programming remain elusive. This study investigates the impact of gestational protein restriction (PR) on fetal hypothalamic development, focusing on the formation of neuronal populations regulating appetite and energy balance. Using a rat isocaloric PR model (8% protein preconception, 4% during gestation), we examined hypothalamic development at gestational days 15 and 17-critical stages for cell fate determination and differentiation. We measured maternal, fetal, and placental weights, and maternal plasma amino acid concentrations. Then, we performed single-cell RNA-seq to assess the impact on neuronal differentiation and uncover mechanisms, which were further investigated via EdU-labeling, immunohistochemistry, and RNAscope. Additionally, we assessed mTOR signaling and analyzed methylation patterns in the Pomc gene. Gestational PR reduced maternal concentrations of essential amino acids, impaired fetal growth, and selectively disrupted the differentiation of ISL1-precursors into POMC neurons, while sparing NPY precursor differentiation. This correlated with downregulated differentiation genes and disrupted mTOR signaling, linked to decreased maternal branched-chain amino acids and altered expression of the amino acid transporter Lat1. Epigenetic alterations in the Pomc promoter but not its enhancers may contribute to the phenotype. Adequate protein intake is crucial for POMC differentiation in the fetal arcuate nucleus. Further studies should investigate additional developmental windows to optimize dietary recommendations for at-risk pregnancies.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14261-14285"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and Relationship Between Homocysteine and H₂S in Ischemic Stroke.","authors":"Weizhuo Lu, Jiyue Wen","doi":"10.1007/s12035-025-04968-5","DOIUrl":"10.1007/s12035-025-04968-5","url":null,"abstract":"<p><p>Homocysteine (Hcy), a sulfur-containing amino acid, is an important intermediate product of methionine metabolism. Hcy can be either metabolized to cysteine, a precursor for glutathione synthesis and hydrogen sulfide (H₂S) production, or regenerated back to methionine. Besides, the Hcy metabolism is central to supply methyl groups, which are essential for DNA methylation. In the transsulfuration pathway of Hcy metabolism, Hcy is metabolized to form cysteine and H₂S by catalytic enzymes, containing cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). Hcy metabolism-related enzymes and coenzymes, such as vitamin B6, vitamin B12, and folic acid, are closely related to hyperhomocysteinemia (HHcy), which is frequently accompanied by reduced H₂S content. An accumulating study has revealed that HHcy is a risk factor for ischemic stroke, while H₂S, served as a gaseous mediator at the physiological level, has protective effects against ischemic stroke. This review outlined the literature data from recent research related to Hcy metabolism and H₂S production and described the roles and relationship among Hcy metabolism and H₂S in ischemic stroke.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14613-14626"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial Responses to MSC-EVs Treatment in Animal and Cellular Models of Ischemic Stroke: a Systematic Review with Meta-analysis.","authors":"Luis Pedro Bernardi, Thomas Hugentobler Schlickmann, Giovanna Carello-Collar, Marco Antonio De Bastiani, Eduardo Rigon Zimmer, Elizandra Braganhol, Francieli Rohden, Diogo Onofre Souza","doi":"10.1007/s12035-025-05025-x","DOIUrl":"10.1007/s12035-025-05025-x","url":null,"abstract":"<p><p>The modulation of microglial reactivity has emerged as a potential target for developing ischemic stroke therapies. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) possess immunomodulatory properties that may influence microglial responses following ischemia. However, individual studies assessing this influence have provided limited results. Therefore, we conducted a systematic review and meta-analysis to investigate whether MSC-EVs treatment alters microglial responses in animal and cellular models of ischemic stroke. In accordance with the PRISMA 2020 statement, we searched PubMed, Web of Science, and EMBASE until January 2025 for studies assessing cellular and molecular parameters of microglial reactivity following MSC-EVs treatment in models of ischemic stroke. We estimated treatment effects using a random-effects meta-analysis of standardized mean differences and estimated heterogeneity via the I² statistic. The risk of bias was assessed using the SYRCLE questionnaire. The search identified 386 studies, 35 of which met the inclusion criteria. In animal models, MSC-EVs reduced the number, surface area, and fluorescence intensity of Iba1⁺ cells, as well as the number of Iba1⁺ cells co-expressing the pro-inflammatory markers CD16, CD32, CD85, and iNOS. Conversely, MSC-EVs increased the number of Iba1⁺ cells co-expressing the anti-inflammatory markers Arg-1 and CD206. In cellular models, we observed decreased concentrations of TNF-α, IL-1β, and IL-6 in the culture medium. Our meta-analysis consolidates the immunomodulatory effects of MSC-EVs on microglial responses to ischemia, underscoring the potential of microglia-specific therapeutics in the development of MSC-EVs-based and regenerative treatments for ischemic stroke.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"14834-14857"},"PeriodicalIF":4.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}