Pub Date : 2026-01-15Epub Date: 2025-11-10DOI: 10.1016/j.jneuroim.2025.578805
Chiara Marotta , Elisabetta Rolla , Martina Fabris , Rossana Domenis , Jérôme Honnorat , Donatella Iacono , Giuseppe Aprile , Mariarosaria Valente , Alberto Vogrig
Immune checkpoint inhibitors (ICIs) have radically improved cancer therapy but are associated with a spectrum of immune-related adverse events (irAEs), including infrequent (1–3 %) neurological complications. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances antitumor immunity but may disrupt self-tolerance, leading to autoimmune phenomena. This case report describes a patient with triple metachronous malignancies (cerebral hemangioblastoma, clear cell renal carcinoma, and non-small cell lung cancer, NSCLC), who developed glial fibrillary acidic protein (GFAP)-antibody-associated autoimmune encephalitis following pembrolizumab therapy initiated as NSCLC treatment. The clinical course was marked by subacute neurocognitive decline followed by new-onset refractory status epilepticus (NORSE). Diagnostic workup revealed GFAP antibodies in cerebrospinal fluid as well as serum, with no evidence of tumor progression or infectious causes. Although GFAP astrocytopathy has been rarely linked to ICIs, this appears to be the first report manifesting with NORSE. The temporal association with cancer immunotherapy, the presence of GFAP autoantibodies, and a positive steroid response collectively suggest that ICI-induced immune dysregulation is the primary disease mechanism. This report, in conjunction with other isolated descriptions form the literature with other antibody specificities, paves the way to a new spectrum of etiologies for NORSE, namely iatrogenic causes related to cancer immunotherapy.
{"title":"Iatrogenic NORSE: Immune checkpoint inhibitor-related anti-GFAP autoimmune astrocytopathy","authors":"Chiara Marotta , Elisabetta Rolla , Martina Fabris , Rossana Domenis , Jérôme Honnorat , Donatella Iacono , Giuseppe Aprile , Mariarosaria Valente , Alberto Vogrig","doi":"10.1016/j.jneuroim.2025.578805","DOIUrl":"10.1016/j.jneuroim.2025.578805","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have radically improved cancer therapy but are associated with a spectrum of immune-related adverse events (irAEs), including infrequent (1–3 %) neurological complications. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances antitumor immunity but may disrupt self-tolerance, leading to autoimmune phenomena. This case report describes a patient with triple metachronous malignancies (cerebral hemangioblastoma, clear cell renal carcinoma, and non-small cell lung cancer, NSCLC), who developed glial fibrillary acidic protein (GFAP)-antibody-associated autoimmune encephalitis following pembrolizumab therapy initiated as NSCLC treatment. The clinical course was marked by subacute neurocognitive decline followed by new-onset refractory status epilepticus (NORSE). Diagnostic workup revealed GFAP antibodies in cerebrospinal fluid as well as serum, with no evidence of tumor progression or infectious causes. Although GFAP astrocytopathy has been rarely linked to ICIs, this appears to be the first report manifesting with NORSE. The temporal association with cancer immunotherapy, the presence of GFAP autoantibodies, and a positive steroid response collectively suggest that ICI-induced immune dysregulation is the primary disease mechanism. This report, in conjunction with other isolated descriptions form the literature with other antibody specificities, paves the way to a new spectrum of etiologies for NORSE, namely iatrogenic causes related to cancer immunotherapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578805"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513088","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}
Autoimmune cerebellar ataxia (ACA), whether paraneoplastic, classically associated with PCA-1 autoimmunity, or non-paraneoplastic, causes substantial morbidity. Antibodies inform clinical decisions given prognostic differences. The modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) underrepresent cerebellar change. We aimed to characterize seropositive ACA, compare PCA-1 with other seropositive cases, identify predictors of poor function, and compare outcome measures.
Methods
We performed a retrospective cohort study of adults with seropositive ACA at Massachusetts General Brigham (2004–2025). We compared anti-PCA-1 positive with other seropositive cohorts. Time to wheelchair dependence was estimated by Kaplan-Meier and compared by log-rank. Univariable Cox models identified predictors. Outcomes were assessed with mRS, CASE, and Brief Ataxia Rating Scale (BARS).
Results
Nineteen patients (median age 66.3 years; 68.4 % female) were included. Eleven (57.9 %) were anti-PCA-1 positive and all of them were paraneoplastic. Tubo-ovarian serous carcinoma was most common (63.6 %). The anti-PCA-1 positive group was more often female (90.9 % vs. 37.5 % p = 0.04), had worse BARS at last follow up (20 vs. 9.5 p < 0.01), and had higher wheelchair dependence (100 % vs. 37.5 % p < 0.01). Acute onset (< 2 weeks) and PCA-1 positivity were associated with wheelchair dependence. BARS monitored symptoms more precisely than mRS or CASE.
Conclusion
In this seropositive ACA cohort, PCA-1 autoimmunity was associated with wheelchair dependence despite immunotherapy and cancer treatment. Acute onset may predict severe decline. A cerebellar symptom specific measure such as BARS may assess clinical change better than mRS or CASE for monitoring ACA.
自身免疫性小脑性共济失调（ACA），无论是与典型的PCA-1自身免疫相关的副肿瘤性，还是非副肿瘤性，都会导致大量的发病率。鉴于预后差异，抗体可为临床决策提供信息。改进的Rankin量表（mRS）和自身免疫性脑炎临床评估量表（CASE）不能充分反映小脑的变化。我们的目的是表征血清ACA阳性，比较PCA-1与其他血清阳性病例，确定功能不良的预测因素，并比较结果测量。方法：我们对2004-2025年在马萨诸塞州布里格姆总医院（Massachusetts General Brigham）的成人血清ACA阳性患者进行了回顾性队列研究。我们比较了抗pca -1阳性与其他血清阳性的队列。到轮椅依赖的时间用Kaplan-Meier法估计，用log-rank法比较。单变量Cox模型确定了预测因子。结果用mRS、CASE和简短共济失调评定量表（BARS）进行评估。结果共纳入19例患者，中位年龄66.3岁，女性68.4%。抗pca -1阳性11例（57.9%），均为副肿瘤。输卵管卵巢浆液性癌最常见（63.6%）。抗pca -1阳性组多为女性（90.9%比37.5% p = 0.04），最后随访时BARS较差（20比9.5 p < 0.01），轮椅依赖性较高（100%比37.5% p < 0.01）。急性发作（2周）和PCA-1阳性与轮椅依赖有关。BARS比mRS或CASE更精确地监测症状。结论在这个血清ACA阳性的队列中，尽管免疫治疗和癌症治疗，PCA-1自身免疫与轮椅依赖相关。急性发作可预示严重衰退。在监测ACA方面，小脑症状特异性测量（如BARS）可能比mRS或CASE更好地评估临床变化。
{"title":"Characteristics and prognosis of PCA-1 (anti-Yo) autoimmunity and the utility of the Brief Ataxia Rating Scale in a seropositive cerebellar ataxia cohort","authors":"Sophia Cerroni , Yoji Hoshina , Trevor Glenn , Nupur Goel , Bruna Leles Vieira de Souza , Joao Vitor Mahler , Mattia Wruble , Giovanna S. Manzano","doi":"10.1016/j.jneuroim.2025.578812","DOIUrl":"10.1016/j.jneuroim.2025.578812","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune cerebellar ataxia (ACA), whether paraneoplastic, classically associated with PCA-1 autoimmunity, or non-paraneoplastic, causes substantial morbidity. Antibodies inform clinical decisions given prognostic differences. The modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) underrepresent cerebellar change. We aimed to characterize seropositive ACA, compare PCA-1 with other seropositive cases, identify predictors of poor function, and compare outcome measures.</div></div><div><h3>Methods</h3><div>We performed a retrospective cohort study of adults with seropositive ACA at Massachusetts General Brigham (2004–2025). We compared anti-PCA-1 positive with other seropositive cohorts. Time to wheelchair dependence was estimated by Kaplan-Meier and compared by log-rank. Univariable Cox models identified predictors. Outcomes were assessed with mRS, CASE, and Brief Ataxia Rating Scale (BARS).</div></div><div><h3>Results</h3><div>Nineteen patients (median age 66.3 years; 68.4 % female) were included. Eleven (57.9 %) were anti-PCA-1 positive and all of them were paraneoplastic. Tubo-ovarian serous carcinoma was most common (63.6 %). The anti-PCA-1 positive group was more often female (90.9 % vs. 37.5 % <em>p</em> = 0.04), had worse BARS at last follow up (20 vs. 9.5 <em>p</em> < 0.01), and had higher wheelchair dependence (100 % vs. 37.5 % p < 0.01). Acute onset (< 2 weeks) and PCA-1 positivity were associated with wheelchair dependence. BARS monitored symptoms more precisely than mRS or CASE.</div></div><div><h3>Conclusion</h3><div>In this seropositive ACA cohort, PCA-1 autoimmunity was associated with wheelchair dependence despite immunotherapy and cancer treatment. Acute onset may predict severe decline. A cerebellar symptom specific measure such as BARS may assess clinical change better than mRS or CASE for monitoring ACA.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578812"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569196","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}
Autoimmune encephalitis (AE) is increasingly recognized in clinical practice, yet drug-related encephalitic syndromes remain a diagnostic challenge. Immune checkpoint inhibitors (ICIs) are well-established triggers, whereas vascular endothelial growth factor (VEGF) inhibitors such as Bevacizumab are only rarely implicated, with evidence confined to case reports. Awareness of this association is essential as targeted therapies gain prominence in metastatic cancer care.
Case presentation
We describe a 58-year-old woman with hypothyroidism and advanced ovarian carcinoma, who had previously undergone surgery and adjuvant chemotherapy in 2022 and metastasectomy for bowel involvement in 2024. She was in remission under Bevacizumab–chemotherapy combination therapy when, following reoperation for peritoneal adhesions in February 2025, she developed two episodes of transient loss of consciousness. During the attacks, fluctuating blood pressure, visual phenomena, and transient foreign-language speech were observed. MRI initially revealed left occipital leptomeningeal enhancement, and EEG showed lateralized epileptiform discharges and non-convulsive status epilepticus was considered. Although initial events were interpreted as seizure-related changes, follow-up imaging on day 15 revealed persistent abnormalities with new cortical and thalamic FLAIR hyperintensities. Neurological examination demonstrated drowsy consciousness, right homonymous hemianopia, motor aphasia, dystonic posturing of the right hand, and sensory integration deficits. Cerebrospinal fluid cytology, paraneoplastic, and autoimmune antibody panels were negative. Pulse intravenous methylprednisolone was initiated, leading to significant clinical improvement and partial radiologic regression, although word-finding difficulties persisted at last follow-up.
Conclusion
This case illustrates an atypical, steroid-responsive encephalitic syndrome temporally associated with Bevacizumab. Unlike the well-characterized bilateral parieto-occipital patterns of PRES, our patient demonstrated unilateral leptomeningeal and cortical–thalamic involvement. The case underscores the importance of repeated neuroimaging, systematic exclusion of alternative etiologies, and timely immunotherapy in suspected drug-related encephalitis. Accumulation of further cases will be essential to clarify incidence, mechanisms, and optimal management of Bevacizumab-associated encephalitis.
{"title":"Autoimmune encephalitis following bevacizumab therapy in ovarian carcinoma: A case report and review","authors":"Bengül Fatma Gölge , Cansu Sarıkaya , Canan Aykut Bingöl , Berrin Aktekin , Rana Karabudak , Gazanfer Ekinci , Serkan Çelik","doi":"10.1016/j.jneuroim.2025.578804","DOIUrl":"10.1016/j.jneuroim.2025.578804","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune encephalitis (AE) is increasingly recognized in clinical practice, yet drug-related encephalitic syndromes remain a diagnostic challenge. Immune checkpoint inhibitors (ICIs) are well-established triggers, whereas vascular endothelial growth factor (VEGF) inhibitors such as Bevacizumab are only rarely implicated, with evidence confined to case reports. Awareness of this association is essential as targeted therapies gain prominence in metastatic cancer care.</div></div><div><h3>Case presentation</h3><div>We describe a 58-year-old woman with hypothyroidism and advanced ovarian carcinoma, who had previously undergone surgery and adjuvant chemotherapy in 2022 and metastasectomy for bowel involvement in 2024. She was in remission under Bevacizumab–chemotherapy combination therapy when, following reoperation for peritoneal adhesions in February 2025, she developed two episodes of transient loss of consciousness. During the attacks, fluctuating blood pressure, visual phenomena, and transient foreign-language speech were observed. MRI initially revealed left occipital leptomeningeal enhancement, and EEG showed lateralized epileptiform discharges and non-convulsive status epilepticus was considered. Although initial events were interpreted as seizure-related changes, follow-up imaging on day 15 revealed persistent abnormalities with new cortical and thalamic FLAIR hyperintensities. Neurological examination demonstrated drowsy consciousness, right homonymous hemianopia, motor aphasia, dystonic posturing of the right hand, and sensory integration deficits. Cerebrospinal fluid cytology, paraneoplastic, and autoimmune antibody panels were negative. Pulse intravenous methylprednisolone was initiated, leading to significant clinical improvement and partial radiologic regression, although word-finding difficulties persisted at last follow-up.</div></div><div><h3>Conclusion</h3><div>This case illustrates an atypical, steroid-responsive encephalitic syndrome temporally associated with Bevacizumab. Unlike the well-characterized bilateral parieto-occipital patterns of PRES, our patient demonstrated unilateral leptomeningeal and cortical–thalamic involvement. The case underscores the importance of repeated neuroimaging, systematic exclusion of alternative etiologies, and timely immunotherapy in suspected drug-related encephalitis. Accumulation of further cases will be essential to clarify incidence, mechanisms, and optimal management of Bevacizumab-associated encephalitis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578804"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517667","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}
Pub Date : 2026-01-15Epub Date: 2025-11-19DOI: 10.1016/j.jneuroim.2025.578811
Ruoling Jia, Xubin Yao, Qingling Liu, Xun Wang
This study investigates the shared molecular mechanisms between major depressive disorder (MDD) and systemic lupus erythematosus (SLE) through integrated bioinformatics analysis. Analysis of multiple GEO datasets identified 23 common differentially expressed genes (coDEGs), primarily enriched in immune and metabolic pathways. Among 13 high-confidence hub genes derived from protein-protein interaction networks, two biomarkers—KLRB1 and RETN—were consistently selected by machine learning algorithms (including LASSO, SVM, and Random Forest) and validated across independent cohorts. Both biomarkers demonstrated high diagnostic accuracy, with combined AUC values of 0.929 for MDD and 0.948 for SLE. Immune infiltration analysis revealed common reductions in NK cells and elevated monocyte levels in both disorders. KLRB1 expression was positively correlated with NK cell function, while RETN showed disease-specific immune correlations. Gene Set Enrichment Analysis (GSEA) indicated associations between both genes and neurodegeneration-related pathways. Additionally, a predicted ceRNA network suggested potential upstream non-coding RNA regulators. These results underscore dysregulated innate immunity and inflammatory pathways as key common features of MDD and SLE, providing new insights into their diagnosis and therapeutic targeting.
{"title":"Identification of the core genes KLRB1 and RETN as potential shared diagnostic markers for major depressive disorder and systemic lupus erythematosus through bioinformatics and machine learning methodologies","authors":"Ruoling Jia, Xubin Yao, Qingling Liu, Xun Wang","doi":"10.1016/j.jneuroim.2025.578811","DOIUrl":"10.1016/j.jneuroim.2025.578811","url":null,"abstract":"<div><div>This study investigates the shared molecular mechanisms between major depressive disorder (MDD) and systemic lupus erythematosus (SLE) through integrated bioinformatics analysis. Analysis of multiple GEO datasets identified 23 common differentially expressed genes (coDEGs), primarily enriched in immune and metabolic pathways. Among 13 high-confidence hub genes derived from protein-protein interaction networks, two biomarkers—KLRB1 and RETN—were consistently selected by machine learning algorithms (including LASSO, SVM, and Random Forest) and validated across independent cohorts. Both biomarkers demonstrated high diagnostic accuracy, with combined AUC values of 0.929 for MDD and 0.948 for SLE. Immune infiltration analysis revealed common reductions in NK cells and elevated monocyte levels in both disorders. KLRB1 expression was positively correlated with NK cell function, while RETN showed disease-specific immune correlations. Gene Set Enrichment Analysis (GSEA) indicated associations between both genes and neurodegeneration-related pathways. Additionally, a predicted ceRNA network suggested potential upstream non-coding RNA regulators. These results underscore dysregulated innate immunity and inflammatory pathways as key common features of MDD and SLE, providing new insights into their diagnosis and therapeutic targeting.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578811"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569185","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}
Pub Date : 2026-01-15Epub Date: 2025-11-20DOI: 10.1016/j.jneuroim.2025.578807
Claudia Vinciguerra , Giuseppe Montalbano , Valentina Virzì , Nicasio Rini , Christian Messina , Liliana Bevilacqua , Paolo Barone , Maria D’Apolito , Eliana Liberatoscioli , Antonio Di Muzio , Roberto Monastero , Filippo Brighina , Vincenzo Di Stefano
Introduction
Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by neuromuscular impairment. While its motor symptoms are well-documented, its neuropsychological impact remains underexplored. This multicenter retrospective case-control study explores the prevalence of psychopathology in MG patients compared to healthy controls (HCs), analyzing correlations between disease severity and psychiatric disorders.
Methods
We retrospectively analyzed 116 MG patients and 119 HCs from three Italian MG centers. Neuropsychological assessment included the Frontal Assessment Battery (FAB) for executive functions, the Beck Depression Inventory (BDI-II) for depression, the 12-Item Short-Form Health Survey (SF-12) for quality of life, the Insomnia Severity Index (ISI) for sleep disturbances, and the Symptom Checklist-90 Revised (SCL-90-R) for psychological distress. Group differences were assessed using ANOVA. In MG patients, correlations between clinical and neuropsychological measures were explored through Pearson's coefficient, while multivariate logistic regression identified predictors of psychiatric involvement.
Results
MG patients exhibited significantly higher SCL-90 total scores and all subdomains (p ≤ 0.001), more frequent sleep disturbances (p = 0.028), and higher BDI-II scores (p ≤ 0.001) than HCs. Increased steroid dosage correlated with anxiety (r = 0.39, p = 0.04), psychoticism (p = 0.021), and depression (p = 0.015). Regression analysis identified disease severity (OR = 2.14, 95 % CI: 1.30–3.51, p = 0.002) and corticosteroid dosage (OR = 1.78, 95 % CI: 1.12–2.83, p = 0.015) as independent predictors of psychiatric symptoms.
Conclusions
MG patients show a significantly higher psychiatric burden, with disease severity and corticosteroid exposure as key contributors. These findings highlight the need for integrated neuropsychiatric monitoring in MG care.
重症肌无力（MG）是一种以神经肌肉损伤为特征的慢性自身免疫性疾病。虽然其运动症状有充分的记录，但其神经心理影响仍未得到充分探讨。这项多中心回顾性病例对照研究探讨了MG患者与健康对照（hc）相比精神病理学的患病率，分析了疾病严重程度与精神障碍之间的相关性。方法回顾性分析来自意大利三个MG中心的116例MG患者和119例hc。神经心理学评估包括执行功能的正面评估组（FAB）、抑郁症的贝克抑郁量表（BDI-II）、生活质量的12项简短健康调查（SF-12）、睡眠障碍的失眠严重程度指数（ISI）和心理困扰的症状检查表-90修订版（SCL-90-R）。采用方差分析评估组间差异。在MG患者中，通过皮尔逊系数探讨临床和神经心理学测量之间的相关性，而多变量逻辑回归确定了精神疾病累及的预测因子。结果smg组患者SCL-90总分及各子域均高于hc组（p≤0.001），睡眠障碍发生率高于HCs组（p = 0.028）， BDI-II评分高于HCs组（p≤0.001）。类固醇剂量增加与焦虑（r = 0.39, p = 0.04）、精神状态（p = 0.021）和抑郁（p = 0.015）相关。回归分析确定疾病严重程度（OR = 2.14, 95% CI: 1.30-3.51, p = 0.002）和皮质类固醇剂量（OR = 1.78, 95% CI: 1.12-2.83, p = 0.015）是精神症状的独立预测因子。结论smg患者精神负担明显加重，疾病严重程度和皮质类固醇暴露是主要影响因素。这些发现强调了在MG护理中进行综合神经精神监测的必要性。
{"title":"Psychopathology in myasthenia gravis: Results from a multicenter Italian study","authors":"Claudia Vinciguerra , Giuseppe Montalbano , Valentina Virzì , Nicasio Rini , Christian Messina , Liliana Bevilacqua , Paolo Barone , Maria D’Apolito , Eliana Liberatoscioli , Antonio Di Muzio , Roberto Monastero , Filippo Brighina , Vincenzo Di Stefano","doi":"10.1016/j.jneuroim.2025.578807","DOIUrl":"10.1016/j.jneuroim.2025.578807","url":null,"abstract":"<div><h3>Introduction</h3><div>Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by neuromuscular impairment. While its motor symptoms are well-documented, its neuropsychological impact remains underexplored. This multicenter retrospective case-control study explores the prevalence of psychopathology in MG patients compared to healthy controls (HCs), analyzing correlations between disease severity and psychiatric disorders.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 116 MG patients and 119 HCs from three Italian MG centers. Neuropsychological assessment included the Frontal Assessment Battery (FAB) for executive functions, the Beck Depression Inventory (BDI-II) for depression, the 12-Item Short-Form Health Survey (SF-12) for quality of life, the Insomnia Severity Index (ISI) for sleep disturbances, and the Symptom Checklist-90 Revised (SCL-90-R) for psychological distress. Group differences were assessed using ANOVA. In MG patients, correlations between clinical and neuropsychological measures were explored through Pearson's coefficient, while multivariate logistic regression identified predictors of psychiatric involvement.</div></div><div><h3>Results</h3><div>MG patients exhibited significantly higher SCL-90 total scores and all subdomains (<em>p</em> ≤ 0.001), more frequent sleep disturbances (<em>p</em> = 0.028), and higher BDI-II scores (p ≤ 0.001) than HCs. Increased steroid dosage correlated with anxiety (<em>r</em> = 0.39, <em>p</em> = 0.04), psychoticism (<em>p</em> = 0.021), and depression (<em>p</em> = 0.015). Regression analysis identified disease severity (OR = 2.14, 95 % CI: 1.30–3.51, <em>p</em> = 0.002) and corticosteroid dosage (OR = 1.78, 95 % CI: 1.12–2.83, <em>p</em> = 0.015) as independent predictors of psychiatric symptoms.</div></div><div><h3>Conclusions</h3><div>MG patients show a significantly higher psychiatric burden, with disease severity and corticosteroid exposure as key contributors. These findings highlight the need for integrated neuropsychiatric monitoring in MG care.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578807"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569195","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}
Pub Date : 2026-01-15Epub Date: 2025-10-17DOI: 10.1016/j.jneuroim.2025.578777
Hengchang Ren , Jinyuan Li , Mei Ding , Wenli Yu
The incidence of brain injury in sepsis patients has been as high as 70 %, which has been a significant cause of septic patients' death. However, the pathophysiology of brain injury in sepsis is multifactorial and inconclusive. There are no clear reasons or effective treatments for brain injury induced by sepsis. The experiment aims to research how Hydrogen sulfide (H2S) affects sepsis-induced brain injury. Male ICR mice developed sepsis via cecal ligation and puncture (CLP). Isodose H₂S was administered before operation and at 1、12 h post-operation. Zinc protoporphyrin IX (ZnPPIX, a HO-1 inhibitor) was intraperitoneally injected 1 h before surgery. After an operation, the survival rate of 7 days was observed and recorded. Morris water maze and Y-maze were applied to evaluate cognitive function. The expression level of Bad and Bcl-2 and neuronal apoptosis by TUNEL assay in the hippocampus were assessed. We used different methods to measure the protein expression and mRNA levels of heme oxygenase-1(HO-1), high-mobility group box 1 (HMGB1) and the activity of HO-1 in hippocampus neurons. The rate of survivors and cognitive impairment of septic mice were markedly improved after H2S treatment, and the brain injury in septic mice such as pathological damage and the expression change of Bad and Bcl-2 significantly alleviated. We discovered that the useful effects of H2S on brain injury in septic mice were related to the decreased level of HMGB1 in the hippocampus. In addition, H2S treatment alleviated brain injury of septic mice by promoting the expression and activity of HO-1. Moderate exogenous H2S treatment would be a potential treatment to relieve sepsis brain injury.
{"title":"Hydrogen sulfide (H₂S) ameliorates sepsis-induced brain injury by upregulating heme oxygenase-1 (HO-1) to inhibit high-mobility group box 1 (HMGB1) release","authors":"Hengchang Ren , Jinyuan Li , Mei Ding , Wenli Yu","doi":"10.1016/j.jneuroim.2025.578777","DOIUrl":"10.1016/j.jneuroim.2025.578777","url":null,"abstract":"<div><div>The incidence of brain injury in sepsis patients has been as high as 70 %, which has been a significant cause of septic patients' death. However, the pathophysiology of brain injury in sepsis is multifactorial and inconclusive. There are no clear reasons or effective treatments for brain injury induced by sepsis. The experiment aims to research how Hydrogen sulfide (H<sub>2</sub>S) affects sepsis-induced brain injury. Male ICR mice developed sepsis via cecal ligation and puncture (CLP). Isodose H₂S was administered before operation and at 1、12 h post-operation. Zinc protoporphyrin IX (ZnPPIX, a HO-1 inhibitor) was intraperitoneally injected 1 h before surgery. After an operation, the survival rate of 7 days was observed and recorded. Morris water maze and Y-maze were applied to evaluate cognitive function. The expression level of Bad and Bcl-2 and neuronal apoptosis by TUNEL assay in the hippocampus were assessed. We used different methods to measure the protein expression and mRNA levels of heme oxygenase-1(HO-1), high-mobility group box 1 (HMGB1) and the activity of HO-1 in hippocampus neurons. The rate of survivors and cognitive impairment of septic mice were markedly improved after H<sub>2</sub>S treatment, and the brain injury in septic mice such as pathological damage and the expression change of Bad and Bcl-2 significantly alleviated. We discovered that the useful effects of H<sub>2</sub>S on brain injury in septic mice were related to the decreased level of HMGB1 in the hippocampus. In addition, H<sub>2</sub>S treatment alleviated brain injury of septic mice by promoting the expression and activity of HO-1. Moderate exogenous H<sub>2</sub>S treatment would be a potential treatment to relieve sepsis brain injury.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578777"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458609","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}
Pub Date : 2026-01-15Epub Date: 2025-11-23DOI: 10.1016/j.jneuroim.2025.578815
Vera Fominykh , Irina Kovaleva , Ekaterina Aksenova , Elena Kondrasheva , Narine Arzumanian , Dmitrii Averchenkov , Sergey Lapin , Vladimir Nazarov , Anna Moshnikova , Mikhail Levin , Alena Prusova , Larisa Burygina , Lev Brylev , Angelina Khannanova
Background
Autoimmune encephalitis (AE) comprises a group of immune-mediated central nervous system disorders and can present with psychiatric symptoms. This study aimed to prospectively identify and characterize the AE group in first psychotic episode (FEP) at the tertiary psychiatric hospital using clinical and instrumental data in combination with modified algorithm for AE in FEP; and retrospectively evaluate current diagnostic algorithms for AE and autoimmune psychosis (AP) based on obtained empirical data.
Methodology
We consecutively assessed all FEP patients admitted to psychiatric hospital according to inclusion-exclusion criteria. In all included patient's clinical picture was assessed, serum and cerebrospinal fluid (CSF) were taken at the acute stage of disorders. CSF oligoclonal bands, cytosis and protein level were tested in all CSF samples. Serum antineuronal antibodies (Abs) to intracellular antigens, NMDA, CASPR2, LGi1, GABAb, AMPA1,2, GAD Abs, thyroid serology, ANA, dsDNA Abs were measured. After the warning signs assessment, the second set of analyses were performed in patients with “red flags” and/or positive laboratory tests: CSF antineuronal antibodies (NMDA, CASPR2, LGi1, GABAb, AMPA1,2, GAD Abs), brain MRI, and oncological screening. AE diagnosis was made by Graus criteria. Immunosuppressive treatment was used in AE patients. We assessed the outcome after the treatment, and for all patients after 9–12 months follow-up.
Results
784 consecutive patients underwent the screening procedure as patients referred to the tertiary psychiatric hospital with FEP. After the inclusion/exclusion procedure, 143 patients were included in the study. We confirmed AE diagnosis in 5 patients (3.5 % of included patients): anti-AMPH, anti-AMPA 2, anti-GABAb, anti-yo AE, and AE with CSF antineuronal antibodies. 1 out of 5 patients died in the acute stage, 3 have good outcomes and return to work.
Conclusion
We revealed 3.5 % AE in the FEP cohort in an East-European tertiary psychiatric hospital. No clinical “red flags” were detected in 1 patient. In 1 patient Ab was detected only in CSF. AE criteria + “red flags” assessment help to reveal 4 out 5 cases. 1 case was found at serum screening and confirmed by CSF analysis. Our results supported the necessity of valid “red flags” panel, serum and CSF antibody testing in the FEP cohort at admission for improving AE diagnostics in FEP.
{"title":"Autoimmune encephalitis in first episode psychosis: Prospective non-interventional longitudinal study in tertiary psychiatric center","authors":"Vera Fominykh , Irina Kovaleva , Ekaterina Aksenova , Elena Kondrasheva , Narine Arzumanian , Dmitrii Averchenkov , Sergey Lapin , Vladimir Nazarov , Anna Moshnikova , Mikhail Levin , Alena Prusova , Larisa Burygina , Lev Brylev , Angelina Khannanova","doi":"10.1016/j.jneuroim.2025.578815","DOIUrl":"10.1016/j.jneuroim.2025.578815","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune encephalitis (AE) comprises a group of immune-mediated central nervous system disorders and can present with psychiatric symptoms. This study aimed to prospectively identify and characterize the AE group in first psychotic episode (FEP) at the tertiary psychiatric hospital using clinical and instrumental data in combination with modified algorithm for AE in FEP; and retrospectively evaluate current diagnostic algorithms for AE and autoimmune psychosis (AP) based on obtained empirical data.</div></div><div><h3>Methodology</h3><div>We consecutively assessed all FEP patients admitted to psychiatric hospital according to inclusion-exclusion criteria. In all included patient's clinical picture was assessed, serum and cerebrospinal fluid (CSF) were taken at the acute stage of disorders. CSF oligoclonal bands, cytosis and protein level were tested in all CSF samples. Serum antineuronal antibodies (Abs) to intracellular antigens, NMDA, CASPR2, LGi1, GABAb, AMPA1,2, GAD Abs, thyroid serology, ANA, dsDNA Abs were measured. After the warning signs assessment, the second set of analyses were performed in patients with “red flags” and/or positive laboratory tests: CSF antineuronal antibodies (NMDA, CASPR2, LGi1, GABAb, AMPA1,2, GAD Abs), brain MRI, and oncological screening. AE diagnosis was made by Graus criteria. Immunosuppressive treatment was used in AE patients. We assessed the outcome after the treatment, and for all patients after 9–12 months follow-up.</div></div><div><h3>Results</h3><div>784 consecutive patients underwent the screening procedure as patients referred to the tertiary psychiatric hospital with FEP. After the inclusion/exclusion procedure, 143 patients were included in the study. We confirmed AE diagnosis in 5 patients (3.5 % of included patients): anti-AMPH, anti-AMPA 2, anti-GABAb, anti-yo AE, and AE with CSF antineuronal antibodies. 1 out of 5 patients died in the acute stage, 3 have good outcomes and return to work.</div></div><div><h3>Conclusion</h3><div>We revealed 3.5 % AE in the FEP cohort in an East-European tertiary psychiatric hospital. No clinical “red flags” were detected in 1 patient. In 1 patient Ab was detected only in CSF. AE criteria + “red flags” assessment help to reveal 4 out 5 cases. 1 case was found at serum screening and confirmed by CSF analysis. Our results supported the necessity of valid “red flags” panel, serum and CSF antibody testing in the FEP cohort at admission for improving AE diagnostics in FEP.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578815"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615378","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}
Baló's concentric sclerosis (BCS) is a rare demyelinating disorder with concentric ring lesions on MRI, which can mimic tumefactive demyelinating lesions (TDL), especially present in tumefactive multiple sclerosis (TMS). Recent neuropathological studies suggest the involvement of activated microglia and astrocytes in BCS lesion expansion. However, advanced imaging techniques like Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have not been fully utilized to differentiate BCS from other TDL or explore their metabolic differences.
Methods
We retrospectively analyzed MRI data from 12 BCS patients (mean age 29.6 years, 50 % male) and 16 patients with TDL (mean age 30.9 years, 37.5 % male). MRS and QSM data were stratified into acute/subacute and chronic phases. Long echo-time acquisitions (TE =144 ms) were used for metabolite ratio analysis, while short echo-time (TE =35 ms) allowed absolute quantification of 34 metabolites. Lesion, peri-lesional, and normal-appearing white matter (NAWM) regions were compared. Patients tested positive for MOG or AQP4 were excluded.
Results
In long echo-time MRS, BCS lesions demonstrated lower Cho/Cr (p = 0.0029) and Cho/NAA (p = 0.019) ratios compared to TDL, indicating greater axonal preservation and lower cellular turnover in BCS. When compared to their respective NAWM, BCS lesions exhibited significantly reduced NAA/Cr (p = 0.001) and TDL reduced NAA/Cr (p = 0.002), Cho/Cr (p = 0.001), and increased Cho/NAA (p < 0.0001). Absolute quantification showed increased myo-inositol in BCS lesions, while TDL showed increased glutamate metabolism. Layer-wise QSM analysis revealed a centrifugal gradient in BCS lesions, with the core exhibiting the highest susceptibility.
Conclusion
BCS presents distinct metabolic and structural features compared to TDL, with biomarkers such as lower Cho/Cr ratios, elevated myo-inositol, and centrifugal QSM gradients, which may enhance diagnostic accuracy and provide insight into lesion expansion.
{"title":"Advanced quantitative MRI reveals a unique pattern of metabolic alterations and iron-pathology linked to glial activation in Baló's concentric sclerosis","authors":"Christina-Athanasia Dempegioti , Giorgos Broumpoulis , Maria-Evgenia Brinia , Ioannis Papadopoulos , Efstratios Karavasilis , Maria-Eleftheria Evangelopoulos , Leonidas Stefanis , Christine Stadelmann , Georgios Velonakis , Constantinos Kilidireas , Aigli G. Vakrakou","doi":"10.1016/j.jneuroim.2025.578798","DOIUrl":"10.1016/j.jneuroim.2025.578798","url":null,"abstract":"<div><h3>Background</h3><div>Baló's concentric sclerosis (BCS) is a rare demyelinating disorder with concentric ring lesions on MRI, which can mimic tumefactive demyelinating lesions (TDL), especially present in tumefactive multiple sclerosis (TMS). Recent neuropathological studies suggest the involvement of activated microglia and astrocytes in BCS lesion expansion. However, advanced imaging techniques like Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have not been fully utilized to differentiate BCS from other TDL or explore their metabolic differences.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed MRI data from 12 BCS patients (mean age 29.6 years, 50 % male) and 16 patients with TDL (mean age 30.9 years, 37.5 % male). MRS and QSM data were stratified into acute/subacute and chronic phases. Long echo-time acquisitions (TE =144 ms) were used for metabolite ratio analysis, while short echo-time (TE =35 ms) allowed absolute quantification of 34 metabolites. Lesion, peri-lesional, and normal-appearing white matter (NAWM) regions were compared. Patients tested positive for MOG or AQP4 were excluded.</div></div><div><h3>Results</h3><div>In long echo-time MRS, BCS lesions demonstrated lower Cho/Cr (<em>p</em> = 0.0029) and Cho/NAA (<em>p</em> = 0.019) ratios compared to TDL, indicating greater axonal preservation and lower cellular turnover in BCS. When compared to their respective NAWM, BCS lesions exhibited significantly reduced NAA/Cr (<em>p</em> = 0.001) and TDL reduced NAA/Cr (<em>p</em> = 0.002), Cho/Cr (p = 0.001), and increased Cho/NAA (<em>p</em> < 0.0001). Absolute quantification showed increased myo-inositol in BCS lesions, while TDL showed increased glutamate metabolism. Layer-wise QSM analysis revealed a centrifugal gradient in BCS lesions, with the core exhibiting the highest susceptibility.</div></div><div><h3>Conclusion</h3><div>BCS presents distinct metabolic and structural features compared to TDL, with biomarkers such as lower Cho/Cr ratios, elevated myo-inositol, and centrifugal QSM gradients, which may enhance diagnostic accuracy and provide insight into lesion expansion.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578798"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482174","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}
Pub Date : 2026-01-15Epub Date: 2025-10-21DOI: 10.1016/j.jneuroim.2025.578772
Xixi Chen , Baojun Huang , Jianya Xiang , Hai Lin , Liqun Yang , Wujun Geng
MicroRNA-126 (miR-126) has emerged as a potential key regulator in ischemic stroke. Yet, its exact mechanism of action is still unexplored. This study aims to investigate whether miR-126 targets and regulates the low-density lipoprotein receptor-related protein (LRP6), an important co-receptor in the Wnt/β-catenin signaling pathway, to reduce ischemic brain injury in mice. C57BL/6 J mice were randomly divided into Sham group, Middle Cerebral Artery Occlusion (MCAO) group, MCAO+miR-126 antagomir group, MCAO+ antagomir NC group, MCAO+miR-126 agomir group and MCAO + agomir NC group. The Garcia nervous system score assessed the neurobehavior of the mice. Infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the extent of cerebral ischemia-reperfusion injury was assessed by Nissl staining. The miR-126 level was detected by real-time PCR, and the apoptosis index was detected by Western blot. A luciferase reporter assay was applied to demonstrate that LRP6 is the target protein of miR-126. The increased expression of miR-126 in MCAO mice inhibits the Wnt/LRP6/β-catenin pathway and enhances neuronal apoptosis. Inhibition of miR-126 alleviates the infarct area, motor ability damage, and apoptosis in MCAO mice. Additionally, Western blot results and luciferase reporter assay showed that inhibition of miR-126 activates the Wnt/β-catenin signaling pathway via LRP6. Our data suggest that inhibition of microRNA-126 attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway.
{"title":"Inhibition of microRNA-126-3p attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway","authors":"Xixi Chen , Baojun Huang , Jianya Xiang , Hai Lin , Liqun Yang , Wujun Geng","doi":"10.1016/j.jneuroim.2025.578772","DOIUrl":"10.1016/j.jneuroim.2025.578772","url":null,"abstract":"<div><div>MicroRNA-126 (miR-126) has emerged as a potential key regulator in ischemic stroke. Yet, its exact mechanism of action is still unexplored. This study aims to investigate whether miR-126 targets and regulates the low-density lipoprotein receptor-related protein (LRP6), an important co-receptor in the Wnt/β-catenin signaling pathway, to reduce ischemic brain injury in mice. C57BL/6 J mice were randomly divided into Sham group, Middle Cerebral Artery Occlusion (MCAO) group, MCAO+miR-126 antagomir group, MCAO+ antagomir NC group, MCAO+miR-126 agomir group and MCAO + agomir NC group. The Garcia nervous system score assessed the neurobehavior of the mice. Infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the extent of cerebral ischemia-reperfusion injury was assessed by Nissl staining. The miR-126 level was detected by real-time PCR, and the apoptosis index was detected by Western blot. A luciferase reporter assay was applied to demonstrate that LRP6 is the target protein of miR-126. The increased expression of miR-126 in MCAO mice inhibits the Wnt/LRP6/β-catenin pathway and enhances neuronal apoptosis. Inhibition of miR-126 alleviates the infarct area, motor ability damage, and apoptosis in MCAO mice. Additionally, Western blot results and luciferase reporter assay showed that inhibition of miR-126 activates the Wnt/β-catenin signaling pathway via LRP6. Our data suggest that inhibition of microRNA-126 attenuates ischemic stroke by targeting endogenous neuroprotective receptor LRP6 in the Wnt/β-catenin signaling pathway.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578772"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419762","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}
Pub Date : 2026-01-15Epub Date: 2025-11-06DOI: 10.1016/j.jneuroim.2025.578801
Alexandra L. Palmer , Ruiqi Wang , Yohan R. Zonta , Zachary D.J. Bailey , Hedwich F. Kuipers , Shalina S. Ousman
Astrocytes play essential roles during homeostasis as structural and functional components of tripartite synapse signaling, blood brain barrier integrity, and neurotransmitter buffering. However, these glia can become reactive in diseases such as multiple sclerosis (MS), where they can exacerbate pro-inflammatory environments by recruiting and promoting immune cell activity through secretion of cytokines and chemokines and possibly antigen presentation. What is incompletely known are the molecular regulators of astrocyte activation. Variable levels of Cst3 mRNA and Cystatin C (CysC) protein have been recorded in a variety of MS tissues, and CysC plays a detrimental role in the experimental autoimmune encephalomyelitis (EAE) model of MS. Further, CysC promotes glial fibrillary acidic protein (Gfap) expression, and contributes to the number of GFAP-positive cells during development. As such, we investigated if CysC is expressed by astrocytes in MS and EAE central nervous system (CNS) cord tissue, and what the functional consequence may be of CysC expression in these glia. We found that CysC is robustly expressed by astrocytes in MS and EAE CNS tissues, that CysC contributes to cytokine and chemokine production by mixed glial cells enriched in astrocytes, and that these CysC-impacted secretory factors can promote cytokine production by CD4+ T cells in vitro. Thus, CysC expression in astrocytes contributes to activation of these glial cells.
{"title":"Cytokine and chemokine production by astrocytes is influenced by Cystatin C","authors":"Alexandra L. Palmer , Ruiqi Wang , Yohan R. Zonta , Zachary D.J. Bailey , Hedwich F. Kuipers , Shalina S. Ousman","doi":"10.1016/j.jneuroim.2025.578801","DOIUrl":"10.1016/j.jneuroim.2025.578801","url":null,"abstract":"<div><div>Astrocytes play essential roles during homeostasis as structural and functional components of tripartite synapse signaling, blood brain barrier integrity, and neurotransmitter buffering. However, these glia can become reactive in diseases such as multiple sclerosis (MS), where they can exacerbate pro-inflammatory environments by recruiting and promoting immune cell activity through secretion of cytokines and chemokines and possibly antigen presentation. What is incompletely known are the molecular regulators of astrocyte activation. Variable levels of <em>Cst3</em> mRNA and Cystatin C (CysC) protein have been recorded in a variety of MS tissues, and CysC plays a detrimental role in the experimental autoimmune encephalomyelitis (EAE) model of MS. Further, CysC promotes glial fibrillary acidic protein (<em>Gfap</em>) expression, and contributes to the number of GFAP-positive cells during development. As such, we investigated if CysC is expressed by astrocytes in MS and EAE central nervous system (CNS) cord tissue, and what the functional consequence may be of CysC expression in these glia. We found that CysC is robustly expressed by astrocytes in MS and EAE CNS tissues, that CysC contributes to cytokine and chemokine production by mixed glial cells enriched in astrocytes, and that these CysC-impacted secretory factors can promote cytokine production by CD4<sup>+</sup> T cells in vitro. Thus, CysC expression in astrocytes contributes to activation of these glial cells.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578801"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517670","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}
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