Inflammation最新文献

{"title":"Nicotine-Induced Transient Activation of Monocytes Facilitates Immunosuppressive Macrophage Polarization that Restrains T Helper 17 Cell Expansion.","authors":"Lei Zhan, Siwei Luo, Han Wang, Junxia Wang, Xiaowei Pan, Yun Lin, Baofeng Jin, Yaoxing Liang, Chen Peng","doi":"10.1007/s10753-024-02191-3","DOIUrl":"10.1007/s10753-024-02191-3","url":null,"abstract":"<p><p>Macrophages in smoking environment exhibit a distinct immunosuppressive phenotype, but the mechanisms that allow nicotine to \"educate\" macrophages are incompletely understood. Here, we identified that nicotine transiently activates and subsequently deactivates monocytes, leading to reduced anti-infective capability of macrophages. This deactivation results in a suppression of IL-17-producing cell expansion through decreased IL-1β production. Mechanistically, nicotine induces the expression of IRAK-M in macrophages, which inhibits NF-κB signaling and restrains NLRP3 inflammasome-mediated IL-1β production. Moreover, the induction of IRAK-M by nicotine is mediated through α7 nAChR binding, which activates downstream STAT3 and AKT signaling pathways. Targeting the interaction between nicotine and α7 nAChR can decrease IRAK-M expression and restore LPS-mediated NLRP3 inflammasome-driven IL-1β production. Collectively, these findings elucidate how nicotine modulates macrophage function through complex signaling mechanisms, ultimately impacting their anti-infective responses and inflammatory processes.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2313-2322"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UVB Induces Sympathetic Nervous System Activation and Norepinephrine Secretion to Regulate The Skin Color of Mice Through the β2-AR/AP-1 Pathway in Epidermal Keratinocytes.","authors":"Qirui Deng, Xinyan Liu, Xiujuan Wen, Hao Huang, Hongfeng Tang","doi":"10.1007/s10753-024-02221-0","DOIUrl":"10.1007/s10753-024-02221-0","url":null,"abstract":"<p><p>The aim of this study was to investigate how ultraviolet B (UVB) light regulates AP-1 expression via the β2-adrenergic receptor (β2-AR) in epidermal keratinocytes, which in turn regulates melanin synthesis in melanocytes, thereby modulating downstream melanin production in skin hair follicles and altering mouse skin color. We established a UV-irradiated mouse model to investigate the effects of UV radiation on changes in skin color. By measuring changes in the expression of genes related to cutaneous sympathetic nerves, norepinephrine synthesis and melanin synthesis, we investigated the relationship between β2-AR expression and cutaneous melanogenesis and determined the localization of β2-AR in cells. The results of the siRNA-mediated transfection of keratinized cells with downregulated β2-AR expression were further verified in vitro. Our results suggest that UVB alters the color of the dorsal skin in mice by activating the AP-1/IL-6 pathway, which triggers the sympathetic release of norepinephrine, thereby increasing β2-AR expression in keratinocytes. Overall, our study improves the current understanding of how UVB light influences skin color changes and highlights the complex interplay between ultraviolet radiation and skin physiology.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2704-2719"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA-seq Reveals Increased and Activated Post-Capillary Venule Endothelial Cells in Erythrodermic Psoriasis.","authors":"Xiaoyan Wu, Yun Luo, Leying Liu, Changxu Han, Yuhua Liu, Zhenying Zhang","doi":"10.1007/s10753-024-02216-x","DOIUrl":"10.1007/s10753-024-02216-x","url":null,"abstract":"<p><p>Erythrodermic psoriasis (EP) is a life-threatening variant of psoriasis. In this study, we contrasted the vascular endothelial cells (ECs) in EP lesions against those in psoriasis vulgaris and healthy controls. Utilizing single-cell RNA sequencing, immunofluorescence, and flow cytometry on human and mouse samples, we observed a marked increase and activation of EP ECs, which upregulated genes relative to angiogenesis, leukocyte adhesion and antigen presentation. This was particularly evident in the subpopulation post-capillary venules (PCV), especially the cluster from EP. Cell-cell communication studies revealed intensified interactions between PCV and leukocytes, mediated by SELE and ICAM1, predominantly in EP. Trajectory analysis suggested differentiation direction of venules-PCV-CAP. 1 with a concomitant reduction in NF2R2 expression. Elevated and activated PCVs were found in EP patient biopsies and mouse models. These findings underscore the significance of PCV in EP pathogenesis, presenting new therapeutic avenues for this debilitating disease.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2640-2649"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andrographolide Attenuates Myocardial Ischemia-Reperfusion Injury in Mice by Up-Regulating PPAR-α.","authors":"Shenjie Zhang, Ying Ye, Qi Li, Juan Zhao, Rongrong Song, Chao Huang, Xu Lu, Chen Huang, Le Yin, Qingsheng You","doi":"10.1007/s10753-024-02193-1","DOIUrl":"10.1007/s10753-024-02193-1","url":null,"abstract":"<p><p>Andrographolide (AGP), a bioactive diterpene lactone, is an active constituent extracted from Andrographis paniculata. It has many biological activities, such as antioxidant, antitumor, antivirus, anti-inflammation, hepatoprotection, and cardioprotection. The aim of the present study is to investigate the cardioprotective effects of AGP in a mouse model of myocardial ischemia-reperfusion injury (MIRI). Adult male C57BL/6 J mice were pre-treated orally with AGP (25 mg/kg) for six days. After 30 min of the left anterior descending coronary artery occlusion followed by 24 h of reperfusion, mice received an additional dose of AGP. The results showed that: (i) AGP pretreatment significantly reduced myocardial infarct size and cardiac injury biomarkers in MIRI mice and improved left ventricular ejection fraction (EF) and fractional shortening (FS); (ii) AGP pretreatment attenuated MIRI-induced oxidative stress imbalance in MIRI mice by increasing total antioxidant capacity (T-AOC) and reducing the levels of hydrogen peroxide (H₂O₂), nitric oxide (NO), malondialdehyde (MDA), and dihydroethidium (DHE); (iii) AGP pretreatment increased Bcl-2 expression and decreased caspase-3 and Bax expression in ischemic myocardial tissue, along with a reduction in TUNEL-positive cells. Further analysis showed that stimulation by I/R decreased peroxisome proliferator-activated receptor-α (PPAR-α) expression in ischemic cardiac tissue, which was prevented by AGP administration. Moreover, administration of the PPAR-α antagonist GW6471 (1 mg/kg) abolished the protective effect of AGP on oxidative stress and apoptosis in the ischemic heart tissue of mice stimulated by ischemia-reperfusion. Taken together, these results suggest that AGP attenuates MIRI-induced cardiac injury by up-regulating PPAR-α expression, thereby preventing oxidative stress and cellular apoptosis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2341-2354"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircIRAK3 Promotes Neutrophil Extracellular Trap Formation by Improving the Stability of ELANE mRNA in Sepsis.","authors":"Yao Lu, Huang Wu, Yuanyuan Luo, Wenjun Xia, Denglian Sun, Ruichi Chen, Zeqing Miao, Weiwei Zhang, Yang Yu, Aiqing Wen","doi":"10.1007/s10753-024-02206-z","DOIUrl":"10.1007/s10753-024-02206-z","url":null,"abstract":"<p><p>Excessive formation of neutrophil extracellular traps (NETs) has been shown to exacerbate inflammatory injury and organ damage in patients with sepsis. Circular RNAs (circRNAs) abnormally expressed in immune cells of sepsis patients, and play an important role in the pathogenesis of dysregulated immune responses. However, the functions of circRNAs in NET formation during sepsis remain unknown. Here, we identified circIRAK3, a novel circRNA that was upregulated in peripheral blood neutrophils of sepsis patients. Combining clinical data, we revealed that elevated circIRAK3 was positively correlated with blood NET levels. Furthermore, knockdown and overexpression in differentiated HL-60 (dHL-60) neutrophil-like cells demonstrated that circIRAK3 promoted NET formation. In addition, we found that circIRAK3 promoted NET formation via positively regulating elastase expression in dHL-60 cells when treated with inflammatory stimuli. Mechanistically, circIRAK3 directly interacted with ELAVL1 to improve ELANE mRNA stability and consequently promote elastase protein expression. In summary, our study reveals that circIRAK3 promotes NET formation in sepsis by increasing ELANE mRNA levels.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2503-2515"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Triamcinolone Acetonide Protects Against Light-Induced Retinal Degeneration by Activating Anti-Inflammatory STAT6/Arg1 Signaling in Microglia.","authors":"Xiangcheng Tang, Wei Liu, Jia Liang, Xingfei Zhu, Xiangyu Ge, Dong Fang, Lirong Ling, Fanglan Yuan, Kun Zeng, Qingshan Chen, Guoming Zhang, Lili Gong, Shaochong Zhang","doi":"10.1007/s10753-024-02224-x","DOIUrl":"10.1007/s10753-024-02224-x","url":null,"abstract":"<p><p>Microglia are highly specialized resident macrophages in the central nervous system that play a pivotal role in modulating neuroinflammation. Microglial plasticity is essential for their function, allowing them to polarize into proinflammatory M1-like or anti-inflammatory M2-like phenotypes. However, the mechanisms driving M1 and M2 microglial induction during retinal degeneration remain largely unexplored. In addition, drugs that regulate retinal microglial polarity have not been fully investigated. The synthetic glucocorticoid triamcinolone acetonide (TA) is widely utilized in ophthalmology clinics for its anti-inflammatory properties. Here, we investigated microglial polarity in a light-induced retinal degeneration mouse model, along with the effects and mechanisms of intravitreal injection of TA on microglial polarity, retinal inflammation, and visual function following light damage (LD). Our findings demonstrated that LD induced a pro-inflammatory M1 microglial signature, with levels of M1 marker proteins in the retina increasing in a time-dependent manner following LD. Intravitreal TA treatment mitigated LD-induced retinal inflammation, photoreceptor death, and retinal blood vessel leakage, and preserved retinal responsiveness to light stimuli. Mechanistically, TA suppressed the proinflammatory microglial phenotype while promoting the anti-inflammatory phenotype by activating the signal transducer and activator of transcription 6/arginase1 (STAT6/Arg1) signaling pathway. These results reveal a new mechanism by which TA protects the retina from LD by shifting microglia toward an anti-inflammatory state through the STAT6/Arg1 axis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2837-2838"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement Molecule C3a Exacerbates Early Brain Injury After Subarachnoid Hemorrhage by Inducing Neuroinflammation Through the C3aR-ERK-P2X7-NLRP3 Inflammasome Signaling Axis.","authors":"Yuanyuan Ming, Panpan Zhao, Hongwei Zhang, Ziyuan Zhang, Zhengqian Huang, Le Zhang, Yong Sun, Xiangdong Li","doi":"10.1007/s10753-024-02155-7","DOIUrl":"10.1007/s10753-024-02155-7","url":null,"abstract":"<p><p>An important aspect of the pathophysiology of early brain damage (EBI) after subarachnoid hemorrhage (SAH) is inflammasome-mediated neuroinflammation. It has been demonstrated that C3aR activation exacerbates neuronal damage in a number of neurological disorders. This study aims to explore the role of C3a in activating the NLRP3 inflammasome and exacerbating neuroinflammation after SAH. Preprocessing of RNA-seq transcriptome datasets using bioinformatics analysis, and screening of differentially expressed genes between SAH patients and healthy individuals from the GEO database. Internal carotid artery puncture was performed to establish SAH models in rats and mice. SAH grading, neurological scoring, brain water content, behavioral analysis, and assessments using ELISA, Western blot, immunofluorescence, and immunohistochemistry were conducted. An in vitro model of SAH was induced in BV-2 cells treated with heme (200 μM). The mechanism of C3a in post-SAH neuroinflammation was studied by interfering with and inhibiting C3aR. Results showed that the expression of C3aR was upregulated in the GEO dataset (serum of SAH patients) and identified as a key differential gene in SAH. Further, elevated levels of C3a were found in the cerebrospinal fluid of clinically collected SAH patients. In the cerebral cortex and/or serum of SAH rats, expression of C3a, IL-1β, IL-6, TNF-α, CD11b, and Ki67 were significantly increased, while IL-10 was significantly decreased. Correlation analysis revealed that C3a showed negative correlation with IL-10 and positive correlation with IL-1β, IL-6, TNF-α, CD11b, and Ki67. After stimulation with heme, protein levels of C3a increased in BV-2 cells. Interfering with C3aR significantly reduced LDH release, IL-1β secretion, Caspase1 activation, levels of NLRP3 expression and ASC oligomerization, and ATP release after heme stimulation in BV-2. Subsequently, the addition of inhibitors of ERK1/2 phosphorylation demonstrated that C3a promotes ATP efflux by activating ERK1/2 phosphorylation, thereby activating P2X7. Further addition of JNJ-55308942 (a P2X7R antagonist) revealed that C3a activated the NLRP3 inflammasome via P2X7. Finally, administering SB290157 (a C3aR inhibitor) in vivo effectively alleviated brain edema, reduced mortality, improved Garcia score, ameliorated motor dysfunction, and suppressed inflammation and NLRP3 inflammasome activation in mice after SAH. Overall, C3a exacerbates EBI-associated NLRP3 inflammasome and neuroinflammation via the C3aR-ERK-P2X7 pathway after SAH. Inhibiting C3aR may serve as a one possible treatment approach to alleviate SAH after EBI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"1791-1810"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble Urokinase-Type Plasminogen Activator Receptor and Inflammatory Biomarker Response with Prognostic Significance after Acute Neuronal Injury - a Prospective Cohort Study.","authors":"Antti Sajanti, Santtu Hellström, Carolyn Bennett, Abhinav Srinath, Aditya Jhaveri, Ying Cao, Riikka Takala, Janek Frantzén, Fredrika Koskimäki, Johannes Falter, Seán B Lyne, Tomi Rantamäki, Jussi P Posti, Susanna Roine, Miro Jänkälä, Jukka Puolitaival, Sulo Kolehmainen, Romuald Girard, Melissa Rahi, Jaakko Rinne, Eero Castrén, Janne Koskimäki","doi":"10.1007/s10753-024-02185-1","DOIUrl":"10.1007/s10753-024-02185-1","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI) are severe conditions impacting individuals and society. Identifying reliable prognostic biomarkers for predicting survival or recovery remains a challenge. Soluble urokinase type plasminogen activator receptor (suPAR) has gained attention as a potential prognostic biomarker in acute sepsis. This study evaluates suPAR and related neuroinflammatory biomarkers in serum for brain injury prognosis. This prospective study included 31 aSAH, 30 IS, 13 TBI, and three healthy controls (n = 77). Serum samples were collected on average 5.9 days post-injury, analyzing suPAR, IL-1β, cyclophilin A, and TNFα levels using ELISA. Outcomes were assessed 90 days post-injury with the modified Rankin Scale (mRS), categorized as favorable (mRS 0-2) or unfavorable (mRS 3-6). Statistical analyses included 2-tailed t-tests, Pearson's correlations, and machine learning linear discriminant analysis (LDA) for biomarker combinations. Elevated suPAR levels were found in brain injury patients compared to controls (p = 0.017). Increased suPAR correlated with unfavorable outcomes (p = 0.0018) and showed prognostic value (AUC = 0.66, p = 0.03). IL-1β levels were higher in the unfavorable group (p = 0.0015). LDA combinatory analysis resulted a fair prognostic accuracy with canonical equation = 0.775[suPAR] + 0.667[IL1-β] (AUC = 0.77, OR 0.296, sensitivity 93.1%, specificity 53.1%, p = 0.0007). No correlation was found between suPAR and CRP or infection status. Elevated suPAR levels in acute brain injury patients were associated with poorer outcomes, highlighting suPAR's potential as a prognostic biomarker across different brain injury types. Combining IL-1β with suPAR improved prognostic accuracy, supporting a multimodal biomarker approach for predicting outcomes.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2217-2229"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide N-oxide Inhibits Microglial Pyroptosis by Upregulating Mitophagy and Alleviates Neural Damage in Rats after TBI.","authors":"Xiaoyan Li, Lan Luo, Pengyu Duan, Yonghong Bi, Yao Meng, Xiaoqian Zhang, Weiyu Feng, Zhehao Jin, Kun Zuo, Xiangcheng Zhao, Bing Zhang","doi":"10.1007/s10753-024-02171-7","DOIUrl":"10.1007/s10753-024-02171-7","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is a severe injury characterized by neuroinflammation and oxidative stress. NAMO (Nicotinamide n-oxide) has anti-inflammatory and inhibits microglial overactivation in neurological disorders. However, the role and mechanism of NAMO in microglial pyroptosis after TBI are unknown. The aim of this study was to investigate the effects of NAMO on TBI and its potential mechanisms through in vivo and in vitro models. In this study, western blot assays were performed by extracting brain tissue mitochondria, and the results showed that NAMO promoted the expression of mitophagy-associated proteins (p62, LC3B, and TOMM20), reduced ROS levels, and inhibited pyroptosis-associated proteins (NLRP3, GSDMD, GSDMD-N, and Caspase-1) and inflammatory cytokines (IL-1β and IL-18). We followed up with immunofluorescence co-localization of GSDMD and IBA 1, which showed that NAMO inhibited microglial pyroptosis. In addition, NAMO promoted neurological recovery after TBI. In vitro experiments showed that NAMO upregulated mitophagy, improved mitochondrial dysfunction, and reduced ROS levels in microglia following lipopolysaccharide (LPS) + adenosine triphosphate (ATP) stimulation in HMC3 cells. We also found that NAMO inhibited pyroptosis-related proteins. To further illustrate whether NAMO affects pyroptosis through mitophagy, we applied the mitophagy inhibitor Mdivi-1 in both in vivo and in vitro models. The results showed that Mdivi-1 reversed NAMO's inhibitory effect on microglial pyroptosis. Taken together, our findings demonstrate that NAMO improves neurological recovery by inhibiting microglial pyroptosis through upregulation of mitophagy, suggesting that NAMO could be a potential therapeutic agent for TBI.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2009-2021"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement Inhibition in Chronic Subdural Hematoma Fluid.","authors":"Niklas Marklund, Shaian Zolfaghari, Gustaf Westerberg, Karsten Ruscher, Elisabet Englund, Henrietta Nittby Redebrandt","doi":"10.1007/s10753-024-02210-3","DOIUrl":"10.1007/s10753-024-02210-3","url":null,"abstract":"<p><strong>Background: </strong>Emerging data suggest a complex pathophysiology of chronic subdural hematoma (CSDH) to which an inflammatory response might contribute. The complement system is activated in acute traumatic setting, although its role in CSDH is unknown. To investigate the complement system in CSDH pathophysiology, we analyzed blood and hematoma fluid biomarkers, as well as immunohistochemistry of the CSDH membrane and dura.</p><p><strong>Materials and methods: </strong>We simultaneously collected CSDH fluid and peripheral blood from 20 CSDH patients at the time of surgery. Biopsies of the dura mater and the CSDH capsule were obtained and analyzed by immunohistochemistry for C5b-C9 or C5a deposition. Biomarkers of inflammation and complement activation were analyzed by a 21-multiplex assay, including Adiponectin, Clusterin, Complement factor C9 and CRP. Complement factor C5a was analyzed separately by a commercial R-plex electrochemiluminescence assay.</p><p><strong>Results: </strong>Ten biomarkers differed significantly between peripheral blood and paired CSDH of which two were significantly increased in CSDH fluid (Clusterin and Cystatin C). Eight of the significantly altered biomarkers were significantly decreased in CSDH fluid, including C5a, Complement 9 and Adiponectin. There was no immunoreactivity for C5a or the C5b-C9 membrane attack complex in the dura or CSDH membrane.</p><p><strong>Conclusions: </strong>In CSDH levels of the complement inhibitor Clusterin were increased, whereas levels of C5a and C9 were decreased. Membrane attack complex C5b-C9 was not detected in the membrane or dura surrounding the CSDH. Inhibition of complement could lead to reduced clearance of debris in the CSDH as well as secondary inflammatory reactions.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"2563-2571"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12336071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}