Journal of neuroimmunology最新文献

{"title":"Comparative efficacy of rituximab versus azathioprine in the treatment of MOG antibody-associated disease (MOGAD)","authors":"Sedat Şen ,&nbsp;Murat Kürtüncü ,&nbsp;Serkan Demir ,&nbsp;Tuncay Gündüz ,&nbsp;Ezgi Demirel ,&nbsp;Melih Tütüncü ,&nbsp;Cihat Uzunköprü ,&nbsp;Damla Cetinkaya Tezer ,&nbsp;Ferah Kızılay ,&nbsp;Belgin Petek Balcı ,&nbsp;Gökhan Arslan ,&nbsp;Caner Feyzi Demir ,&nbsp;Nazire Pınar Acar Özen ,&nbsp;Yeşim Beckmann ,&nbsp;İpek Güngör Doğan ,&nbsp;Uğur Uygunoğlu ,&nbsp;Serkan Özakbaş ,&nbsp;Mesrure Köseoğlu ,&nbsp;Haluk Gümüş ,&nbsp;Nuray Bilge ,&nbsp;Aslı Tuncer","doi":"10.1016/j.jneuroim.2025.578686","DOIUrl":"10.1016/j.jneuroim.2025.578686","url":null,"abstract":"<div><h3>Background</h3><div>Azathioprine (AZA) and rituximab (RTX) are frequently used drugs in the treatment of Myelin Oligodendrocyte Glycoprotein Associated Disease (MOGAD).</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate the efficacy and safety data of AZA and RTX treatments in MOGAD.</div></div><div><h3>Methods</h3><div>Patients diagnosed according to the 2023 MOGAD diagnostic criteria and receiving AZA or RTX treatment were included in the study.</div></div><div><h3>Results</h3><div>In 142 patients included in the study, the female/male value was 1.2. The rate of OCB positivity in MOGAD patients was 22.6 %. Patients on RTX had higher EDSS values than patients on AZA. However, the RTX group demonstrated a more pronounced improvement in disability, reflected by a greater negative trend in the ΔEDSS values. The attack-free rate was 78 % in the RTX group and 68 % in the AZA group during their treatment period. Both groups had no difference in the time of the first attack. The main factor affecting the time to first attack was having a higher EDSS at the time of treatment initiation. The survival analysis found that EDSS scores improved significantly in patients treated with RTX.</div></div><div><h3>Conclusion</h3><div>Although survival analyses for both treatments appear to be similar, using RTX provides better EDSS scores.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"407 ","pages":"Article 578686"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictors from systemic and neuro-inflammation in amyotrophic lateral sclerosis: A monocentric experience","authors":"Ilaria Martinelli ,&nbsp;Cecilia Simonini ,&nbsp;Elisabetta Zucchi ,&nbsp;Giulia Gianferrari ,&nbsp;Roberta Bedin ,&nbsp;Andrea Ghezzi ,&nbsp;Jessica Mandrioli","doi":"10.1016/j.jneuroim.2025.578683","DOIUrl":"10.1016/j.jneuroim.2025.578683","url":null,"abstract":"<div><div>While the role of systemic and neuroinflammatory players is actually consolidated in amyotrophic lateral sclerosis (ALS) pathogenesis, a representative and reliable panel of inflammatory prognostic biomarkers is still lacking.</div><div>This retrospective study on 182 ALS patients from the Modena ALS Center, investigates biomarkers of axonal injury (neurofilaments) and microglial and astrocytic activation (SerpinA1, TREM2, CHI3L1, OPN and S100B, respectively). In a subpopulation of patients, we examined blood count-derived parameters, including the Systemic-Immune-Inflammation index (SII), Systemic Inflammation Response Index (SIRI) and Aggregate Systemic Inflammation Index (AISI). All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups.</div><div>SerpinA1_CSF was significantly lower in females [4.43 μg/ml (IQR 2.76–6.3) vs 5.61 μg/ml (IQR 3.39–9.16),<em>p</em> = 0.032], while SII indexes was oppositely distributed [higher in females, 540.67 (IQR 363.05–807.24) vs 384.89 (IQR 307.5–578.52),<em>p</em> = 0.015]. In univariate survival analysis, without overcoming neurofilaments, SIRI (HR 1.43, 95 %CI 1.03–1.966,<em>p</em> = 0.03), AISI (HR 1.002, 95 %CI 1.001–1.003, <em>p</em> = 0.002) and SII (HR 1.001, 95 %CI 1.0003–1.001,<em>p</em> = 0.003) impact negatively on survival, with AISI retaining its power at multivariate analysis (HR 1.002, 95 %CI 1.0004–1.001,<em>p</em> = 0.012). SerpinA1_CSF levels influenced survival only for females (HR 1.042, 95 %CI 1.0065–1.078,<em>p</em> = 0.02), in a similar manner of SIRI (HR 1.483, 95 %CI 1.082–2.0334,<em>p</em> = 0.014) and SII (HR 1.00099, 95 %CI 1.0008–1.003,<em>p</em> = 0.001).</div><div>Our data revealed the influence of sex on survival by SerpinA1_CSF, CHI3L1_CSF and systemic biomarkers in females. However, both neurofilaments and CHI3L1_CSF outperform the other neuroinflammatory biomarkers at predicting rate of disease progression, so the prognostic meaning of these measure alone remains unconclusive, requiring larger collaborative studies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578683"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microscopic Polyangiitis With a Twist: A Rare Case of CRAO and Brainstem Infarction","authors":"Govind Singh Mann,&nbsp;Saurabh Nandwani,&nbsp;Nitin Jain","doi":"10.1016/j.jneuroim.2025.578685","DOIUrl":"10.1016/j.jneuroim.2025.578685","url":null,"abstract":"<div><div>Microscopic polyangiitis (MPA) is a rare autoimmune vasculitis of small vessels. It is often linked with ANCA. Central retinal artery occlusion (CRAO) is characterized by sudden, painless vision loss and is typically connected with embolic or inflammatory causes. However, limited literature exists on its association with MPA. This case report uniquely highlights a 50 year old patient diagnosed with MPA exhibiting CRAO and brainstem infarct. The report stresses the importance of early recognition of uncommon vascular manifestations, multidisciplinary diagnostic approaches, and the integration of immunosuppressive therapies for optimal management of systemic vasculitis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578685"},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone mitigates NLRP3 inflammasome activation and GSDMD-mediated pyroptosis and enhances the negative regulatory pathways of pyroptosis in microglia","authors":"Mehmet Erdem ,&nbsp;Şeniz Erdem ,&nbsp;Süleyman Caner Karahan ,&nbsp;Ahmet Alver ,&nbsp;Soner Karabulut ,&nbsp;Gökhan Yıldız","doi":"10.1016/j.jneuroim.2025.578684","DOIUrl":"10.1016/j.jneuroim.2025.578684","url":null,"abstract":"<div><div>Microglia are resident immune cells of brain, which serves as a driver of the innate immunity within the central nervous system (CNS). The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex that is critical component of the innate immunity and hyperactivation of inflammasome under various conditions contributing to the pathogenesis of neurodegenerative diseases (NDs). 7,8-Dihydroxyflavone (7,8-DHF) have become the focus of attention in studies on NDs due to exert its neurotrophic effects in the CNS. Recent studies have shown encouraging outcomes targeting immune regulatory and neuroprotective properties. 7,8-DHF is a specific tropomyosin-related kinase receptor B (TrkB) agonist and bioavailable brain-derived neurotrophic factor (BDNF) mimetic, which has immunomodulator properties in the CNS. In the present study, we researched the effects of BDNF mimetic 7,8-DHF on NLRP3 inflammasome activation, GSDMD-mediated pyroptosis, NF-κB signaling, ESCRT-III-dependent plasma membrane repair, and selective autophagy in LPS plus ATP-induced murine N9 microglial cells. These findings demonstrated that BDNF mimetic 7,8-DHF significantly reduced NLRP3 inflammasome activation, decreased active caspase-1 the levels, inhibited secretion of proinflammatory cytokine IL-1β and IL-18 levels through the IκBα/NF-κB axis. Furthermore, we showed that BDNF mimetic 7,8-DHF activated selective autophagy and ESCRT-III-dependent plasma membrane repair, both of which play crucial roles in the negative regulation of NLRP3 inflammasome activation. Our study reveals that BDNF mimetic 7,8-DHF effectively prevents microglial NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by inhibiting IκBα/NF-κB, promoting ESCRT-III-dependent plasma membrane repair and enhancing selective autophagy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578684"},"PeriodicalIF":2.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144580669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piceatannol attenuates chronic unpredictable stress-induced neurobehavioral deficits in mice via SIRT1-mediated modulation of neuroinflammation, oxidative stress, and neurotransmitter imbalance","authors":"Parneet Kaur ,&nbsp;Ojashvi Sharma ,&nbsp;Amarjot Kaur Grewal ,&nbsp;Amit Kumar ,&nbsp;Heena Khan ,&nbsp;Varinder Singh ,&nbsp;Tanveer Singh ,&nbsp;Pragati Silakari ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Sheikh F. Ahmad ,&nbsp;Sabry M. Attia","doi":"10.1016/j.jneuroim.2025.578682","DOIUrl":"10.1016/j.jneuroim.2025.578682","url":null,"abstract":"<div><div>Exposure to chronic unpredictable stress (CUS) serves as the major contributor for the neurobehavioral changes. The current study explores the possible involvement of the SIRT1 pathway in mediating the neuroprotective properties of piceatannol in CUS induced neurobehavioral changes. Molecular docking studies showed binding interactions of piceatannol with SIRT1, suggesting that it may modulate SIRT1 activity. For evaluating effect of CUS and pharmacological interventions on neurobehavioral changes, the mice (Swiss Albino, Male) were subjected to the EPM, TST, FST, SPT, MWM and PA test. In current study, the effect on levels of corticosterone and neurotransmitters (dopamine and serotonin); various parameters of oxidative stress and neuroinflammation; acetylcholinesterase and histological changes in hippocampus and cortex were also assessed. It was observed that piceatannol (10 and 20 mg/kg; <em>p.o</em>) reduced the deleterious impact of CUS on oxidative stress and neuroinflammation; reduced corticosterone and dopamine levels; increased serotonin levels and improved neurobehavioral and histological changes. Pre-treatment with sirtinol (10 mg/kg; <em>i.p.</em>), a SIRT1 inhibitor, greatly reduced the neuroprotective properties of piceatannol. Thus, it may be concluded that activation of SIRT1 pathway may be responsible for the neuroprotective effects of piceatannol on CUS induced neurobehavioral alterations.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578682"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-type voltage-gated calcium channel antibody testing lacks diagnostic value in Lambert-Eaton myasthenic syndrome","authors":"Friederike A. Arlt ,&nbsp;Masoud Majed ,&nbsp;Jack Wu ,&nbsp;Anastasia Zekeridou ,&nbsp;Shahar Shelly ,&nbsp;Vanda A. Lennon ,&nbsp;Sean J. Pittock ,&nbsp;Andrew McKeon ,&nbsp;Christopher J. Klein ,&nbsp;Divyanshu Dubey ,&nbsp;John R. Mills","doi":"10.1016/j.jneuroim.2025.578681","DOIUrl":"10.1016/j.jneuroim.2025.578681","url":null,"abstract":"<div><h3>Introduction/aims</h3><div>Diagnostic evaluation for Lambert-Eaton myasthenic syndrome (LEMS) includes serological testing for voltage-gated calcium channel antibodies (VGCC-P/Q-type [VGCC-PQ] and VGCC-N-type [VGCC-N]). While VGCC-PQ antibodies are well-established biomarkers in LEMS, the clinical utility of VGCC-N antibody testing remains obscure. We aimed to determine the diagnostic value of VGCC-N antibody testing.</div></div><div><h3>Methods</h3><div>A retrospective cross-sectional study was performed. The Mayo Clinic electronic medical record from 1995 to 2021 was reviewed for inclusion of patients fitting clinical electrodiagnostic criteria for LEMS, who were evaluated for serum VGCC antibodies (<em>n</em> = 123). Available sera were additionally tested for SOX1 antibodies (<em>n</em> = 68). Healthy adults were tested for VGCC-PQ and VGCC-N antibodies (<em>n</em> = 122). Clinical performance of each antibody test was evaluated statistically.</div></div><div><h3>Results</h3><div>Among adult LEMS cases, 84.6 % (<em>n</em> = 99/117) tested positive for VGCC-PQ antibody while none of the healthy controls did. In contrast, 20.5 % (<em>n</em> = 24/117) were VGCC-N antibody positive, of which 95.8 % (<em>n</em> = 23/24) co-occurred with VGCC-PQ antibodies. The frequency of isolated VGCC-N antibody positivity was higher in controls than in LEMS (2.5 % [<em>n</em> = 3/122] vs. 0.9 % [<em>n</em> = 1/117]), and pediatric patients had no VGCC-N antibody reactivity. Neither VGCC-N antibody positivity nor titer was predictive of an associated small-cell lung cancer (SCLC-LEMS). By contrast, SOX1-IgG seropositivity associated significantly with SCLC-LEMS.</div></div><div><h3>Discussion</h3><div>Inclusion of VGCC-N antibody testing does not improve diagnostic accuracy for LEMS, nor does it serve as a predictor of LEMS-associated cancers in contrast to SOX1-IgG testing. We recommend the exclusion of VGCC-N antibody testing given its non-specific disease associations and poor positive predictive value in LEMS screening.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578681"},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of plasma IL-33 levels with aggression in schizophrenia: A clinical study","authors":"Qi Zhang ,&nbsp;Li Li ,&nbsp;Zheng Gao ,&nbsp;Xue Li ,&nbsp;Peng Zhang ,&nbsp;Yujing Yang ,&nbsp;Caiyi Zhang","doi":"10.1016/j.jneuroim.2025.578680","DOIUrl":"10.1016/j.jneuroim.2025.578680","url":null,"abstract":"<div><div>Aggression in schizophrenia (SCZ) poses a serious risk to others and complicates treatment. Inflammation has been confirmed to be associated with aggression in SCZ, but specific biomarkers remain unidentified. This study aimed to measure plasma interleukin-33 (IL-33) levels and explore their association with aggression in SCZ for the first time. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IL-33 in SCZ with aggression (SCZ-Ag, <em>n</em> = 31) and non-aggression (NSCZ-Ag, <em>n</em> = 32), and healthy controls (HCs, <em>n</em> = 26). Aggression was measured using the Modified Overt Aggression Scale (MOAS), and clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The results showed that the plasma IL-33 levels were elevated in SCZ-Ag compared with NSCZ-Ag and HCs, with no significant difference between NSCZ-Ag and HCs. In the patient group, partial correlation analysis indicated a positive correlation between IL-33 levels and PANSS total scores, positive symptom subscores, and MOAS total scores. Regression analysis showed that a higher likelihood of aggression in SCZ was associated with elevated plasma IL-33 levels (OR = 1.075, 95 % <em>CI</em>: 1.023–1.129). ROC curve analysis showed that IL-33 (AUC = 0.713, 95 % <em>CI</em>: 0.582–0.844) demonstrated moderate performance in distinguishing SCZ-Ag from NSCZ-Ag. These findings suggest that elevated plasma IL-33 levels are a potential risk factor for aggression in patients with SCZ and are implicated in the clinical symptoms of patients. Increased plasma IL-33 levels may serve as a potential marker for aggression in SCZ. These findings require further validation in future studies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578680"},"PeriodicalIF":2.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network analysis of intrathecally synthesized proteins to unravel mechanisms of disease course in multiple sclerosis","authors":"Nora C. Welsh ,&nbsp;Krista D. DiSano ,&nbsp;Steven C. Pike,&nbsp;Michael Linzey ,&nbsp;Andrew D. Smith III,&nbsp;Andrew R. Pachner,&nbsp;Francesca Gilli","doi":"10.1016/j.jneuroim.2025.578678","DOIUrl":"10.1016/j.jneuroim.2025.578678","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a heterogeneous disease, in both clinical presentation and neuro-immunopathology. Proteins secreted into the cerebrospinal fluid (CSF) can serve as molecular proxies of these pathologies in the central nervous system (CNS) but are biased by leakage of serum proteins into the CSF. Thus, a detailed analysis of intrathecal protein production, i.e., the fraction of CSF protein synthesized locally within the CNS, rather than derived from passive transfer across the blood-CSF barrier, can provide valuable insights into the heterogenous immunological and neurodegenerative processes at play. To understand the dynamic biological processes involved in MS disease course mechanisms, we used network analysis to untangle the intricacies of intrathecally produced protein-to-protein relationships in 60 patients diagnosed with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and primary progressive MS (PMS). These analyses revealed distinct immunological phenotypes linked to inflammation and neurodegeneration in the CNS in each disease course, providing novel insight into the disease course-specific pathophysiology of MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578678"},"PeriodicalIF":2.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraneoplastic bilateral vocal cord paralysis in a patient with anti-Hu syndrome after receiving nivolumab: Case report and literature review","authors":"Seyda Erdoğan ,&nbsp;Elif Peker ,&nbsp;Ahmet Demirkazık ,&nbsp;Nursel Aydın ,&nbsp;Canan Yücesan","doi":"10.1016/j.jneuroim.2025.578679","DOIUrl":"10.1016/j.jneuroim.2025.578679","url":null,"abstract":"<div><div>Bilateral vocal cord paralysis (BVCP), a life-threatening condition often necessitating tracheotomy, has been infrequently reported as a paraneoplastic manifestation. We present the case of a 75-year-old male with small cell lung cancer who experienced distinct episodes of paraneoplastic neurological syndromes. The initial episode, occurring concomitant with the diagnosis of cancer and initiation of chemotherapy, was characterized by epileptic seizures and ataxia, which resolved following treatment with immunotherapy. The subsequent episode, presenting as BVCP, developed after the fourth dose of nivolumab as part of the patient's paraneoplastic syndrome. Brain magnetic resonance imaging revealed bilateral hyperintense lesions in the anterior medulla oblongata on T2/FLAIR-weighted sequences. To the best of our knowledge, this represents the first documented case of paraneoplastic BVCP associated with bilateral bulbar lesions, potentially triggered by immune checkpoint inhibitor therapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578679"},"PeriodicalIF":2.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-223-3p promote microglia “M2” polarization by targeting FOXO3a in subarachnoid hemorrhage","authors":"Xiaolong Yao ,&nbsp;Bizhou Bie ,&nbsp;Zhizhong Wang ,&nbsp;Yingchun Chen ,&nbsp;Liuqing Sheng ,&nbsp;Mingchang Li","doi":"10.1016/j.jneuroim.2025.578677","DOIUrl":"10.1016/j.jneuroim.2025.578677","url":null,"abstract":"<div><h3>Objective</h3><div>Exosome-derived micorRNAs (miRs) play important role in regulation the inflammatory response in subarachnoid hemorrhage (SAH). However, the ability of miR-223-3p, which is enriched in astrocyte-derived exosomes, to regulate FOXO3a in microglia is still unclear.</div></div><div><h3>Methods</h3><div>MiR-223-3p in CSF from SAH patients was measured by qRT–PCR. Rats and BV2 cells were used to establish SAH model. Neurological function was evaluated by the mNSS, rotarod test, and Morris water maze. QRT–PCR and enzyme-linked immunosorbent assay (ELISA) were used to analyze oxidative stress and inflammatory factors interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α). The levels of FOXO3a, TLR4, NLRP3, NF-κB, iNOS, Cox2, Nrf2 and HO-1 were detected by WB. The exosomes were labeled with KPH67, and uptaken by microglia, detecting by IF.</div></div><div><h3>Results</h3><div>Among the miRs involved in SAH, miR-223-3p exhibited one of the greatest change. MiR-223-3p in the brain tissue of SAH rats was upregulated. Moreover, the upregulation of miR-223-3p significantly improved neurological deficits and reduced brain edema. Meanwhile, miR-223-3p reduced the inflammatory factors like IL-1β, IL-6, TNF-α, and decreased oxidative stress, inhibited the activation of NF-κB, TLR4/NLRP3 in microglia by targeting Foxo3a. The “M1” polarization marker, including iNOS, Cox2, TLR4, NLRP3 and NF-κB, in microglia decreased markedly after the overexpression of miR-223-3p. Moreover, miR-223-3p targets FOXO3a and inhibits it expression no matter <em>in vitro</em> or <em>in vivo</em>. <em>In vitro</em>, both miR-223-3p mimics and astrocyte-derived exosomes obviously increased the expression of miR-223-3p in microglia.</div></div><div><h3>Conclusion</h3><div>In SAH, astrocyte-derived exosomes rich in miR-223-3p may regulate the activation and phenotype of microglia by targeting FOXO3a, resulting in the inhibition of inflammatory injury.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578677"},"PeriodicalIF":2.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}