Journal of Neuroinflammation最新文献

{"title":"Coexistence of CN1A autoantibodies in GAD65 encephalitis exacerbates neurodegeneration : Novel autoantibodies in GAD65 encephalitis.","authors":"Annika Breuer, Delara Kamalizade, Tobias Baumgartner, Juliane L Berns, Thoralf Opitz, Franziska S Thaler, Susanne Schoch, Lars Komorowski, Christoph Helmstaedter, Rainer Surges, Albert J Becker, Julika Pitsch","doi":"10.1186/s12974-025-03521-4","DOIUrl":"https://doi.org/10.1186/s12974-025-03521-4","url":null,"abstract":"<p><strong>Background: </strong>Autoantibodies targeting the intracellular 65-kDa isoform of glutamic acid decarboxylase (anti-GAD65) have been associated with a variety of autoimmune-related syndromes involving a spectrum of difficult-to-treat neurological disorders. However, the pathophysiological role of anti-GAD65 in neuroinflammation remains vague. Its understanding may be complicated by the possible pathogenic interaction between anti-GAD65 and potentially coexisting autoantibodies.</p><p><strong>Methods: </strong>We combined a broad spectrum of approaches ranging from antibody-antigen identification, immunoblotting, immunoprecipitation, mass-spectrometry, cell-based assays, subcellular binding pattern analysis in primary neuronal cultures, and immunohistochemistry to in vitro assays of neuronal uptake, viability, and multi-electrode arrays.</p><p><strong>Results: </strong>In anti-GAD65-positive neurological patients, mass-spectrometric analysis revealed cytosolic 5'-nucleotidase 1 A (CN1A syn. NT5C1A) as the most abundant antigen. Subsequent screening of 118 anti-GAD65-positive patients revealed that 32 of them had additional autoantibodies targeting CN1A, which were also present in all available corresponding CSF samples. Limbic encephalitis was more often diagnosed in anti-CN1A/anti-GAD65-positive compared to the anti-GAD65-positive patients. Functionally, incubation of primary hippocampal neurons with anti-GAD65, but not with anti-CN1A, resulted in uptake into GABAergic neurons, neuronal cell death, and increased neuronal network activity. Moreover, simultaneous incubation with both antibodies (anti-CN1A/anti-GAD65) resulted in concomitant intraneuronal uptake in a concentration-dependent manner, which correlated with enhanced autophagy followed by massive neuronal death.</p><p><strong>Conclusion: </strong>GAD65 antibodies directly affect neuronal viability and network activity. Co-existing autoantibodies against CN1A, present in anti-GAD65-positive patients, enhance autophagy and subsequent neuronal death in vitro. Clinically, anti-GAD65-positive patients should be screened for anti-CN1A-associated diseases, and evaluation of anti-CN1A in anti-GAD65-related autoimmune conditions may clarify links between systemic autoimmunity and epilepsy.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"194"},"PeriodicalIF":9.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.","authors":"Dorottya Szabó, Lilla Otrokocsi, Beáta Sperlágh","doi":"10.1186/s12974-025-03509-0","DOIUrl":"https://doi.org/10.1186/s12974-025-03509-0","url":null,"abstract":"<p><p>Immune activation in the prenatal and early postnatal periods is increasingly implicated in the aetiology of neurodevelopmental disorders, such as autism spectrum disorder and schizophrenia, by disrupting critical neurodevelopmental processes. The impact of immune activation on brain development can be influenced by the type, timing, location, and severity of the infection. Viral, bacterial, and parasitic infections, as well as maternal autoimmune diseases, can lead to the activation of the purinergic P2X7 receptors, thereby contributing to neuroinflammation. Upon activation, P2X7 induces the assembly of the NLRP3 inflammasome, leading to the release of the pro-inflammatory cytokine IL-1β. Besides activation of additional inflammatory mediators, excessive IL-1β during critical periods of brain development can disrupt neuronal migration, synapse formation, dendritic morphology and blood-brain barrier integrity, contributing to a range of neurodevelopmental abnormalities. Animal studies have shown that inhibiting the components of the P2X7/NLRP3/IL-1β pathway can mitigate these adverse effects. This review examines the role of the P2X7/NLRP3/IL-1β pathway in mediating the effects of infection and neuronal inflammation on brain development. We discuss the therapeutic potential of targeting this pathway with a balanced approach that reduces long-term neuronal inflammation while preserving essential immune functions.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"192"},"PeriodicalIF":9.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-targeting CSF1R signaling attenuates neurotoxic myeloid activation and preserves photoreceptors in retinitis pigmentosa.","authors":"Jiangmei Wu, Jing Zhang, Bin Lin","doi":"10.1186/s12974-025-03525-0","DOIUrl":"https://doi.org/10.1186/s12974-025-03525-0","url":null,"abstract":"<p><p>Retinitis pigmentosa (RP), a group of inherited retinal diseases characterized by progressive photoreceptor degeneration, features prominent microglial activation and monocyte-derived macrophage infiltration. While colony-stimulating factor 1 receptor (CSF1R) shows diverse roles in regulating microglial survival and behaviors in various neurodegenerative diseases, its functional significance in RP pathogenesis remains unclear. In this study, we observed upregulated CSF1R signaling specifically within disease-associated myeloid cells in the rd10 mouse model of RP. Targeted intervention via intravitreal CSF1R neutralizing antibodies and systemic PLX5622 administration achieved reduced myeloid proliferation and pro-inflammatory cytokine production and greater photoreceptor survival. Notably, CSF1R potentiation using recombinant IL-34 or CSF1 exacerbated neuroinflammation and accelerated photoreceptor degeneration. Mechanistic investigations revealed that infiltrating monocyte depletion by clodronate liposomes significantly reduced macrophage infiltration and preserved visual function. Using CX3CR1^CreER/+/R26^iDTR/+/rd10 mouse model, we observed that diphtheria toxin-mediated microglia ablation preserved retinal function. Overall, our findings demonstrate the prominent role of CSF1R in neurotoxic myeloid activation in the context of RP. Our results provide preclinical proof-of-concept that dual targeting of retinal and peripheral CSF1R pathways may offer a mutation-agnostic therapeutic strategy for inherited retinal degenerations.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"193"},"PeriodicalIF":9.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term stress preconditioning activates sympathetic innervation in the testes to mitigate testicular ischemia-reperfusion injury.","authors":"Liyong Liu, Ruiming Xu, Heshe Li, Yuanchen Ma, Yue Shu, Hongjie Liang, Tao Wang, Jiang Hao, Weiqiang Li, Andy Peng Xiang, Mei Hua Jiang, Weijun Huang","doi":"10.1186/s12974-025-03515-2","DOIUrl":"10.1186/s12974-025-03515-2","url":null,"abstract":"<p><p>Testicular tissues are highly vulnerable to oxidative stress and external insults due to their unique physiological microenvironment; thus, developing protective interventions is critical. We reveal that preconditioning through short-term stress-induced sympathetic nervous system (SNS) activation effectively mitigates testicular ischemia-reperfusion injury (IRI) in mice. Pre-activation of the SNS via diverse stressors markedly reduced seminiferous tubular damage and oxidative biomarkers compared to untreated controls. Mechanistically, the protective effect is mediated by dopamine-beta hydroxylase-expressing neurons in the rostral ventrolateral medulla (DBH^RVLM), which enhance sympathetic innervation in the testes. Optogenetic and chemogenetic approaches confirmed that DBH^RVLM neuron activation elevates testicular norepinephrine levels and attenuates tissue damage. Furthermore, we identify testicular macrophages as one of key mediators of this protection, demonstrating their immunomodulatory response to sympathetic signaling. These results support the \"good stress\" hypothesis, underscoring the beneficial effects of acute stress. Since the short-term stress response is a conserved adaptive mechanism in mammals, our findings suggest that SNS-mediated preconditioning could extend beyond testicular protection, potentially offering therapeutic insights for other oxidative stress-sensitive organs.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"191"},"PeriodicalIF":9.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences on laser-induced choroidal neovascularization and short-chain fatty acid treatment in a mouse model.","authors":"Chufan Yan, Caio Andreeta Figueiredo, Inga-Marie Pompös, Bilge Ugursu, Paula Arribas-Lange, Sergej Skosyrski, Seulkee Yang, Petra Althoff, Norbert Kociok, Antonia M Joussen, Susanne A Wolf","doi":"10.1186/s12974-025-03508-1","DOIUrl":"10.1186/s12974-025-03508-1","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is a leading cause of blindness worldwide, with a clinical presentation that varies between sexes. In late-stage AMD, choroidal neovascularization (CNV) triggers retinal inflammation and degeneration, processes that are exacerbated by an overactive response of retinal microglial cells. Short-chain fatty acids (SCFAs) have emerged as potential treatments for AMD due to their anti-inflammatory properties. In this study, we investigate the effects of SCFA treatment in a laser-induced CNV mouse model, focusing on sex-dependent differences in disease progression and microglial response. Our findings demonstrate distinct sex-specific patterns in the development of CNV and associated pathological hallmarks. SCFA treatment resulted in a slight increase in density of Iba1⁺ microglial cells in females at 3 days post-laser (3dpl), while it prevented an increase in males at 7 dpl, with both sexes showing enhanced microglial ramification. The dynamics of microglial density were likely linked to protective effects on CNV lesion, leakage size, and inflammation, which occurred earlier in females and later in males. At transcriptional level, SCFA showed mixed effects, mainly targeting inflammation resolution, mitochondrial support, and neuronal repair in a sex-dependent manner. In vitro, SCFAs reduced microglial phagocytosis of retinal debris, suggesting a potential anti-inflammatory action. This study underscores the importance of considering sex-specific responses in the development of AMD treatments, such as SCFAs, and highlights the need for personalized therapeutic strategies.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"188"},"PeriodicalIF":9.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated TBK1 promotes ACSL1-mediated microglia lipid droplet accumulation and neuroinflammation in Parkinson's disease.","authors":"Chunlei Han, Huizhi Wang, Moxuan Zhang, Liuliu Wu, Anni Wang, Pengda Yang, Yuan Gao, Chaonan Zhang, Jianing Gao, Tao Xue, Tingting Du, Yucheng Ji, Lin Shi, Chunkui Zhang, Renpeng Li, Yilei Xiao, Jianguo Zhang, Fangang Meng","doi":"10.1186/s12974-025-03517-0","DOIUrl":"10.1186/s12974-025-03517-0","url":null,"abstract":"","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"190"},"PeriodicalIF":9.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profile of microglia following inflammation-sensitized hypoxic-ischemic brain injury in neonatal rats suggests strong contribution to neutrophil chemotaxis and activation.","authors":"Anna-Sophie Bremer, Nico Henschel, Hannah Burkard, Maria Eugenia Bernis, Thomas Ulas, Hemmen Sabir","doi":"10.1186/s12974-025-03516-1","DOIUrl":"10.1186/s12974-025-03516-1","url":null,"abstract":"<p><strong>Background: </strong>Inflammation-sensitized hypoxic-ischemic brain injury significantly contributes to neonatal mortality as affected neonates do not benefit from standard cooling treatments. To get further insight into inflammatory responses involved, we experimentally investigated the immune response of microglia in an inflammation-sensitized neonatal hypoxia-ischemia (HI) model.</p><p><strong>Results: </strong>Transcriptomic analysis of microglia isolated from brains following inflammation-sensitized HI brain injury revealed a strong upregulation of leukocyte recruitment and pro-inflammatory markers. Specifically, markers associated with neutrophil-mediated immune responses and chemotaxis were upregulated in the inflammation-sensitized HI group compared to the non-inflammation-sensitized HI and control groups. Serpine 1 and Selp could be identified as specifically upregulated markers indicating an acute inflammatory condition before HI injury.</p><p><strong>Conclusion: </strong>Our study revealed preliminary data about a microglia population which is primed to recruit peripheral neutrophils to infiltrate the brain and mediate neutrophil immune response. We showed a contribution to neutrophil activation in case of inflammation following HI in the brain. Targeting microglia-mediated neutrophil recruitment can indicate a possible treatment approach in case of inflammation-sensitized HI brain injury.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"189"},"PeriodicalIF":9.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of microglia priming by NLRP3 reduces the impact of early life stress and mild TBI.","authors":"Fabiola Placeres-Uray, Aditi S Gorthy, Maria Dominguez Torres, Coleen M Atkins","doi":"10.1186/s12974-025-03512-5","DOIUrl":"10.1186/s12974-025-03512-5","url":null,"abstract":"<p><p>Although most patients with mild traumatic brain injury (mTBI) experience rapid recovery, some report persistent chronic symptoms such as cognitive dysfunction. One risk factor for prolonged recovery after mTBI is early life stress (ELS). We hypothesized that ELS mediates prolonged cognitive dysfunction after mTBI by exacerbating the NRLP3 inflammasome signaling pathway, and that these effects could be reversed by inhibiting NLRP3.</p><p><strong>Methods: </strong>To test this hypothesis, Sprague Dawley rat pups were maternally separated for 3 h daily from P2-P14. Subsequently, the rats underwent a mild-to-moderate fluid percussion brain injury (1.4 atm) or sham surgery during young adulthood and were then treated with either the NLRP3 inhibitor MCC950 or vehicle.</p><p><strong>Results: </strong>We found that ELS significantly increased microglia and macrophage cell numbers within the hippocampus during mTBI recovery. Quantitative PCR demonstrated that the combination of ELS and mTBI significantly increased levels of HMGB1, TLR4, NLRP3, caspase 1, and IL-1β mRNA levels in the ipsilateral hippocampus at 24 h after injury. This upregulation was persistent and TLR4, NLRP3, caspase 1, and IL-1β levels remained elevated for up to 2 months after injury. Inhibition of the NLRP3 inflammasome with MCC950 reduced this upregulation both 24 h and 2 months after injury. Hippocampal microglia isolated by fluorescence-activated cell sorting demonstrated increased levels of NLRP3 after ELS alone, but not IL-1β. The upregulation in microglial IL-1β required the combination of ELS and mTBI and was ameliorated with MCC950. Additionally, MCC950 treatment improved glucocorticoid receptor downregulation in the hippocampus after ELS, mTBI alone and mTBI + ELS. The combinatory insult of ELS and mTBI also impaired associative fear memory which was prevented with MCC950 treatment.</p><p><strong>Conclusion: </strong>In summary, ELS limits recovery after mTBI by upregulating the expression of NLRP3 inflammasome signaling molecules in microglia. Inhibition of NLRP3 is an effective therapeutic for treating chronic cognitive deficits after ELS and mTBI.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"185"},"PeriodicalIF":9.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of neuronal α1-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING/NF-κB/NLRP3 signaling pathway in Alzheimer's disease mice.","authors":"Bo Li, Li Wang, Yan Xiao, Zhi Tang, Yang Wang, Ting Sun, Xiaolan Qi","doi":"10.1186/s12974-025-03506-3","DOIUrl":"10.1186/s12974-025-03506-3","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is closely associated with the pathological progression of Alzheimer's disease (AD). The α1-adrenergic receptor (ADRA1), a G protein-coupled receptor, has been identified as a critical therapeutic target in inflammatory disorders. However, its precise mechanistic role in AD pathogenesis remains unclear.</p><p><strong>Methods: </strong>To investigate ADRA1's role in AD, we employed 3xTg-AD and wild-type (WT) mice, modulating neuronal ADRA1 expression via intracerebroventricular delivery of adeno-associated viruses. Cognitive function, tau pathology, neuronal morphology, and activation of the STING/NF-κB/NLRP3 signaling pathway were evaluated using behavioral tests, Western blot, Golgi-Cox staining, immunohistochemistry, and immunofluorescence. In vitro AD models were established using Aβ₄₂ oligomer-stimulated SH-SY5Y cells and primary murine neurons, along with SH-SY5Y cells transfected with full-length human tau (SH-SY5Y/htau). Pharmacological antagonists, inhibitors, lentiviral transduction, co-immunoprecipitation, and calcium flux assays were utilized to dissect ADRA1-mediated molecular mechanisms in tauopathy and neuroinflammation.</p><p><strong>Results: </strong>Hippocampal ADRA1 expression was significantly elevated in 10-month-old 3xTg-AD mice. Neuronal ADRA1 knockdown suppressed STING/NF-κB/NLRP3 pathway activation, ameliorated tauopathy and neuroinflammation, restored neuronal structure/function, and improved cognitive deficits in 3xTg-AD mice. Conversely, ADRA1 overexpression in C57/BL6 mice induced tauopathy, neuroinflammation, and cognitive impairment. Mechanistically, ADRA1 interacts with CXCR4 to form heterodimers, triggering cytoplasmic Ca²⁺ overload and subsequent STING/NF-κB/NLRP3 pathway activation.</p><p><strong>Conclusions: </strong>ADRA1 critically mediates tauopathy and neuroinflammation through STING/NF-κB/NLRP3 signaling. These results identify ADRA1 as a promising therapeutic target for AD prevention and treatment.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"187"},"PeriodicalIF":9.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of progressive multiple sclerosis decrease following autologous hematopoietic stem cell transplantation.","authors":"Ida Erngren, Katarina Lundblad, Ivan Pavlovic, Asma Al-Grety, Anders Larsson, Kim Kultima, Joachim Burman","doi":"10.1186/s12974-025-03511-6","DOIUrl":"10.1186/s12974-025-03511-6","url":null,"abstract":"<p><strong>Background: </strong>Autologous hematopoietic stem cell transplantation (AHSCT) has been increasingly used for treatment of relapsing-remitting multiple sclerosis (RRMS). Existing data suggest that AHSCT might alter the natural course of multiple sclerosis (MS) and postpone or even prevent the occurrence of progressive MS. This study aimed to investigate whether three cerebrospinal fluid biomarkers of progressive MS: Galectin-9, GDF-15, and YKL-40, were affected by treatment intervention with AHSCT for RRMS.</p><p><strong>Methods: </strong>RRMS patients treated with AHSCT at Uppsala University Hospital between 2011 and 2018 were considered for participation and included if CSF samples from baseline and at least one follow-up were available. CSF from healthy volunteers was included as controls. Galectin-9 and GDF-15 concentrations were determined with ELISA, and YKL-40 with electrochemiluminescence.</p><p><strong>Results: </strong>The final cohort comprised 45 RRMS patients and 32 controls. At baseline, MS patients had markedly higher CSF concentrations of Galectin-9 and YKL-40 and slightly higher GDF-15 than controls. Following AHSCT, biomarker concentrations decreased from baseline to the 1-year follow-up, with a median (IQR) of 454 (357-553) vs. 408 (328-495) pg/mL (P = 0.0002) for Galectin-9; 49 (38-79) vs. 45 (35 to 75) pg/mL (P = 0.012) for GDF-15, and 100 (54-164) vs. 58 (43-92) ng/mL (P < 0.0001) for YKL-40. Galectin-9 and YKL-40 concentrations decreased further and were even lower at the 2-year follow-up; median (IQR) 408 (328-495) vs. 376 (289-478) pg/mL (P = 0.0009) for Galectin-9; and 62 (37-96) vs. 56 (30-83) ng/mL (P < 0.0001) for YKL-40. Thereafter, the levels of all biomarkers were stable throughout the follow-up.</p><p><strong>Conclusion: </strong>Treatment with AHSCT was associated with sustained reductions in biomarkers linked to progressive MS, indicating its potential not only to achieve lasting remission but also to delay or prevent transition to SPMS. However, additional studies are necessary to confirm these findings and elucidate their long-term clinical significance.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"186"},"PeriodicalIF":9.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}