Inflammation最新文献

{"title":"Acute and Long-Term Consequences of Neonatal NMDA Blockade in the Cx3cr1 Knock-Out Mouse.","authors":"Felipe A Méndez, Mayra Itzel Torres-Flores, Benito Ordaz, Fernando Peña-Ortega","doi":"10.1007/s10753-025-02272-x","DOIUrl":"https://doi.org/10.1007/s10753-025-02272-x","url":null,"abstract":"<p><p>Neuron-microglia communication through the fractalkine pathway is a critical factor mediating microglial proliferation, migration, release of mediators, and clearance of cellular debris, as well as the function of neuronal NMDA receptors. Disruption of the fractalkine-mediated microglia-neuron communication is associated with divergent outcomes, from damaging to protective, in different neurological conditions (including schizophrenia and epilepsy). In the present work we explore the impact of the absence of the fractalkine receptor (CX3CR1) after neonatal blockade of NMDA receptors, which induces acute and long-term alterations in behavior, neuronal integrity and excitability. Wild-type (WT) and Cx3cr1^-/- (KO) mice of both sexes randomly received either a low (0.5 mg/kg) or high dose (1 mg/kg) of MK-801 (NMDA receptor antagonist) or saline, for five consecutive days, during early postnatal development. Neuronal apoptosis was assessed at a midpoint of the pharmacological protocol. Survival and growth rates were determined up to adulthood when innate behaviors, unconditioned anxiety, contextual memory and seizure susceptibility were evaluated, as well as hippocampal local field potential and sensory gating. CX3CR1 depletion and neonatal MK-801 treatment had a synergistic acute effect, increasing neuronal apoptosis and overall mortality. Both factors independently induced long-lasting impairments in the wide array of behavioral tasks assessed during adulthood. However, low MK-801 dose treatment greatly augmented the mortality of pentylenetetrazol-induced seizures in WT mice, an effect prevented by CX3CR1 depletion. MK-801 treatment induced a shift in the power spectrum of the hippocampal local field potential towards higher frequencies that was averted in Cx3cr1^-/- mice by an opposite shift. Our results reveal that CX3CR1 depletion severely increases the vulnerability to neonatal NMDA antagonism with additional complex interactions regarding cognitive and neurophysiological effects, which should be considered in the context of neuron-microglia miscommunication in many neurological disorders including schizophrenia and epilepsy.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995640","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":"A Quinoxaline Derivative as a New Therapeutic Agent for Sepsis through Suppression of TLR4 Signaling Pathways.","authors":"Hamza Hanieh, Manal A Alfwuaires","doi":"10.1007/s10753-025-02292-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02292-7","url":null,"abstract":"<p><p>Sepsis is a severe systemic inflammatory syndrome and one of the leading causes of global morbidity and mortality. Preclinical studies have identified several quinoxaline-based compounds with anti-inflammatory properties, but their effects in sepsis have not been investigated. This study aimed to identify a quinoxaline derivative with anti-inflammatory properties in sepsis. Examining the inflammatory response of primary mouse macrophages to Lipopolysaccharides (LPS) revealed that 2-methoxy-N-(3-quinoxalin-2-ylphenyl)benzamide (2-MQB) is a promising molecule. It suppressed the production of several inflammatory cytokines, including Interleukin-1β (IL-1β), IL-6, IL-12p70, Interferon-γ (IFN-γ), IFN-β, and Tumor necrosis factor-α (TNF-α). Importantly, 2-MQB inhibited the transcriptional activities of Toll-like receptor 4 (TLR4) signaling pathways, including Nuclear factor-κB (NF-κB) and Interferon regulatory factor 3 (IRF3). This was accompanied by lower expression of TLR4, Myeloid differentiation primary response 88 (MyD88), TIR Domain-containing adaptor molecule 1 (Trif), and TNF Receptor-associated factor 3 (Traf3). Additionally, 2-MQB selectively reduced the expression of genes encoding CD80, CD86, and Programmed death-ligand 1 (PD-L1). In vivo, 2-MQB improved mice survival, mitigated tissue damage in the spleen, kidney, and lung, and reduced pro-inflammatory cytokine levels in both LPS-induced endotoxin shock and Cecal ligation and puncture (CLP) models. Notably, 2-MQB decreased the numbers of CD4⁺ and CD8⁺ T cells in the spleen and inhibited TLR4 signaling pathways in LPS-induced endotoxemia. In conclusion, these results introduce the quinoxaline derivative 2-MQB as a potential therapeutic agent for sepsis by inhibiting TLR4 signaling pathways, paving the way for future clinical applications.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144006867","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":"Integrated Analysis of Single-Cell and Transcriptome Data Reveals the Role and Regulatory Mechanisms of Neuroinflammation in Parkinson's Disease.","authors":"Yao Geng, Rui-Yu Wang, Man-Yu Dong, Yi-Lun Qian, Xi-Hui Wang, Wen-Wen Xia, Ying Shen, Ke-Zhong Zhang","doi":"10.1007/s10753-025-02306-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02306-4","url":null,"abstract":"<p><p>There is increasing interest in developing therapeutic interventions aimed at preventing neuroinflammation in Parkinson's disease (PD). However, the specific characteristics of inflammation across different cell types and the underlying mechanisms of PD-related inflammation remain inadequately understood. In this study, we conducted an analysis of single-cell RNA sequencing (scRNA-seq) and microarray data derived from human PD midbrain tissue, specifically focusing on the substantia nigra compacta (SNc). These datasets were sourced from the (GEO) database. We utilized GSVA, GSEA, as well as KEGG and GO analyses to explore transcriptional variations associated with PD. Furthermore, trajectory and SCENIC analyses were conducted to uncover the mechanisms underlying PD progression. Subsequent animal and cellular experiments validated the role of the regulon in regulating neuroinflammation. Results: Our analysis revealed that microglia displayed the highest levels of inflammatory activity, characterized by an increased abundance of microglia in the proinflammatory activated state within the midbrain and SNc of PD patients. This finding was further validated in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The transcription factor STAT3 demonstrated significant upregulation and was implicated in promoting the inflammatory response and activating microglia within the PD context. In the 1-methyl-4-phenylpyridine (MPP +)-induced BV2 cell model, inhibition of STAT3 led to reduced levels of inflammation, hindered STAT3 phosphorylation, and decreased the production of inflammatory factors. Furthermore, the downregulation of P-STAT3 alleviated the harmful effects on SH-SY5Y cells that were cocultured in the conditioned medium. Conclusions: Our study underscored the pivotal role of the transcription factor STAT3 as a central regulator of proinflammatory activation in microglia within PD. These findings offer fresh insights into PD pathogenesis and suggest potential avenues for the development of novel therapeutic strategies.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985040","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":"Inhibition of Macrophage Activation by Minocycline Attenuates CCI-Induced Neuropathic Pain.","authors":"Yan-Zhe Ji, Zhi-Hao Lin, Cai-Xian Liao, Qian Wang, Fang-Yu Chen, Wen-Feng Su, Ya-Yu Zhao, Gang Chen, Zhong-Ya Wei","doi":"10.1007/s10753-025-02300-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02300-w","url":null,"abstract":"<p><p>Neuropathic pain is characterized by a high prevalence and associated with a variety of disorders of the peripheral and central nervous systems. It remains a major challenge for clinical management due to lack effective treatments. Our previous studies have demonstrated that nerve injury-induced neuroinflammation plays a critical role in regulating the development and maintenance of neuropathic pain. In the present study, we found that chronic constriction injury (CCI) led to a significant increase in the number of macrophages at the site of injured nerves. To elucidate the role of macrophage activation in CCI-induced neuropathic pain, we employed chemical agents, including clodronate liposomes, which is known for their ability to deplete macrophages, and minocycline, an inhibitor of macrophage function. Both intravenous injection of liposome-encapsulated clodronate and intrasciatic delivery of minocycline effectively attenuated CCI-induced mechanical and heat hyperalgesia. Furthermore, transfer of polarized M2 macrophages significantly alleviated CCI-induced neuropathic pain, but not under the condition of M1 macrophage transfer. Mechanistically, our findings indicated that pretreatment with minocycline increased the expression level of CD206 but decreased that of IL-1β, while post-polarization treatment markedly decreased the expression level of both. Additionally, an in vitro migration assay revealed that minocycline exerts an inhibitory effect on macrophage migration. In brief, our study elucidates the effect of CCI-induced macrophage activation on neuropathic pain and provides new insights into the potential clinical application of minocycline for managing neuropathic pain.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978148","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":"4,4'-Dimethoxychalcone Mitigates Neuroinflammation Following Traumatic Brain Injury Through Modulation of the TREM2/PI3K/AKT/NF-κB Signaling Pathway.","authors":"Mengran Wang, Rui Zhao, Yue Su, Duhuan Zhai, Hengyan Liang, Lingkun Zhang, Weicheng Wang, Zhichun Wang, Min Qi, Xiaochun Jiang, Shizhang Ling, Guangfu Di","doi":"10.1007/s10753-025-02279-4","DOIUrl":"https://doi.org/10.1007/s10753-025-02279-4","url":null,"abstract":"<p><p>Research on 4,4'-dimethoxychalcone (DMC) in the context of traumatic brain injury (TBI) is extremely limited, and no effective clinical treatments are available to improve outcomes for individuals with TBI. Our study aims to investigate the underlying mechanisms by which DMC may alleviate neuroinflammation and neuronal damage following TBI. This study seeks to provide a theoretical foundation for the development of future pharmacological therapies for TBI. A moderate TBI model was established using the fluid percussion injury (FPI) method. The recovery of neuromotor function following TBI was evaluated using the modified neurological severity score (mNSS), the Morris water maze test, and analysis of cerebral edema. Gene and protein expression levels were quantified using cell viability assays, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. Network pharmacology was employed to predict potential targets of DMC, and gene ontology (GO) analysis along with KEGG pathway enrichment was conducted to predict signaling pathways affected by DMC.DMC treatment significantly improved neuromotor deficits in mice after TBI. In both in vivo and in vitro experiments, DMC suppressed microglial activation and decreased the production and release of inflammatory factors. Additionally, DMC reduced neuronal lesions after TBI. DMC notably decreased the elevated expression of triggering receptor expressed on myeloid cells 2 (TREM2) following TBI. Network pharmacological analysis indicated that DMC's therapeutic effects may be mediated through the PI3K/AKT signaling cascade. These findings indicate that DMC has therapeutic potential for TBI, with significant anti-inflammatory and neuroprotective properties likely mediated by the TREM2/PI3K/AKT/NF-κB signaling cascade.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990155","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":"Proteomic Profiles of Neutrophils from Behcet's Uveitis Patients and their Sex Differences.","authors":"Rong Liu, Qingfeng Wang, Qingyan Jiang, Rui Chang, Yan Zhou, Xingsheng Ye, Xiang Luo, Yujie Lai, Guannan Su, Peizeng Yang","doi":"10.1007/s10753-025-02305-5","DOIUrl":"https://doi.org/10.1007/s10753-025-02305-5","url":null,"abstract":"<p><p>Behcet's uveitis (BU) is one of the most vision-threatening uveitis entities with male-biased incidence and severity. Neutrophil dysfunction has been implicated in the pathogenesis of this disease. However, their proteomic changes are not completely understood. We performed proteomic analysis on peripheral neutrophils from patients with active BU and identified 82 up-regulated and 516 down-regulated differentially expressed proteins (DEPs) compared to healthy controls (HCs). We further performed functional analysis on these DEPs and found that the pathway involved in neutrophil extracellular trap formation was activated, whereas nucleotide metabolism and apoptosis were suppressed. Compared with female patients, male patients presented enhanced pathways associated neutrophil-mediated inflammatory responses and suppressed apoptosis. Additionally, integrative analysis of proteomic profiles and single-cell RNA sequencing (scRNA-seq) data revealed that these sex differences might be related to the enhanced inflammatory response in primed inflammatory and inflammatory neutrophils as well as deficiencies in apoptosis and nucleotide metabolism in ROS-responsive neutrophils. Collectively, our data revealed the proteomic profiles of neutrophils from patients with BU, and their functional changes may play crucial roles in the pathogenesis of this disease and its sex differences.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998879","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":"PTGS2 Silencing Inhibits Ferroptosis in Staphylococcus Aureus-induced Osteomyelitis By Blocking the IL-17A Signaling Pathway.","authors":"Si-Rui Zhou, Wen-Guang Li, Li-Dan Yang, Hao Xiang, Ying Jin, Jian-Bo Feng, Hua-Zhang Xiong, Jiachen Peng","doi":"10.1007/s10753-025-02296-3","DOIUrl":"https://doi.org/10.1007/s10753-025-02296-3","url":null,"abstract":"<p><strong>Objective: </strong>Osteomyelitis caused by Staphylococcus aureus (S. aureus) infection is an inflammatory bone disease characterized by continuous bone destruction, which is difficult to treat. This research aimed to explore the molecular mechanisms of S. aureus-induced osteomyelitis.</p><p><strong>Methods: </strong>Using the GSE166522 and GSE227521 datasets, hub differentially expressed genes (DEGs) were screened by bioinformatics analysis. Hub gene expression levels were validated in S. aureus-induced mouse models. An inhibitor of PTGS2, etoricoxib, was used to assess the role of PTGS2 in the osteomyelitis mouse model. PTGS2 was silenced in an LPS-induced MC3T3-E1 cell model to study its effect on cell function.</p><p><strong>Results: </strong>Six hub genes were screened, including ARG1, TIMP1, NOS2, PTGS2, SOCS3, and IL1B, highly expressed in the S. aureus-induced osteomyelitis model. Etoricoxib treatment attenuated the inflammatory infiltration of tibial tissue in mice with osteomyelitis. In vivo and in vitro, etoricoxib treatment and PTGS2 silencing reduced inflammatory factor (TNF-α, IL-1β, and IL-6) levels. PTGS2 silencing promoted LPS-induced MC3T3-E1 cell viability and inhibited apoptosis and ferroptosis. GPX4 and SLC7A11 protein levels were significantly increased after PTGS2 silencing. Mechanistically, IL-17A intervention significantly counteracted the impact of PTGS2 silencing on cell behaviors and secukinumab combined with PTGS2 silencing more effectively suppressed inflammation and ferroptosis, indicating that PTGS2 impeded the osteomyelitis progression by inhibiting the IL-17A pathway.</p><p><strong>Conclusion: </strong>Silencing PTGS2 reduces ferroptosis in S. aureus-induced osteomyelitis by obstructing the IL-17A pathway, which suggests a new approach for the treatment of osteomyelitis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982029","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":"CLICs Inhibitor IAA94 Alleviates Inflammation and Injury in Septic Liver by Preventing Pyroptosis in Macrophages.","authors":"Jing Liu, Jingwen Hu, Xulei Yao, Mengting Xu, Aini Yuan, Jianan Guo, Cui Wang, Yifei Le, Xingyu Yuan, Dezhao Lu","doi":"10.1007/s10753-025-02304-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02304-6","url":null,"abstract":"<p><p>Macrophage pyroptosis represents a pivotal mechanism underlying acute liver injury during sepsis. Chloride intracellular channel proteins (CLICs) have been linked to inflammatory reflexes, with IAA94 serving as an inhibitor of channel formation characteristic of CLICs. In a mouse model, IAA94 demonstrated efficacy in reducing pro-inflammatory cytokines in liver tissues, decreasing macrophage in the liver, inhibiting the development of the pro-fibrosis phenotype, and alleviating tissue injury. Additionally, IAA94 exhibited inhibitory effects on the activation of NLRP3 inflammasome, leading to the suppression of pyroptosis in J774A.1 cells and the liver. Additionally, IAA94 was observed to impede the interaction between NEK7 and NLRP3. Furthermore, it was observed that the conditioned medium of pyroptotic macrophages treated with IAA94 induced an attenuated inflammatory response in hepatocytes in comparison to that induced by the conditioned medium of pyroptotic macrophages. However, NLRP3 overexpression impeded the beneficial effects of IAA94. In conclusion, IAA94 has the capacity to impede NLRP3 inflammasome formation-mediated pyroptosis by blocking CLICs-mediated chloride efflux and the inhibition of NEK7-NLRP3 interactions, thereby establishing CLICs as a promising therapeutic target against liver inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970088","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":"TFAM Deficiency Triggers mtDNA Leakage and cGAS-STING-Mediated Intestinal Ischemia-Reperfusion Injury.","authors":"Ke Ding, Lele Zhang, Yiguo Zhang, Yixin Jing, Huiyang Liao, Rong Chen, Qingtao Meng","doi":"10.1007/s10753-025-02302-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02302-8","url":null,"abstract":"<p><p>Intestinal Ischemia-Reperfusion (IIR) injury is a common clinical pathophysiological condition, yet the complex molecular mechanisms underlying its pathology remain incompletely understood. This study aims to explore the precise molecular mechanisms of IIR injury, with a focus on the role of the cGAS-STING signaling pathway. Using a mouse IIR model and hypoxia/reoxygenation (HR) model in HT-29 cells and small intestinal organoids, we observed that IIR significantly induces oxidative stress and activates the cGAS-STING pathway, which is associated with exacerbated small intestinal tissue damage and enhanced inflammatory responses. Further investigation revealed that mitochondrial DNA (mtDNA) leakage is a critical trigger for the activation of the cGAS-STING pathway. The introduction of exogenous mtDNA into cells activated the STING pathway and exacerbated cellular damage. In contrast, the depletion of intracellular mtDNA effectively suppressed HR-induced activation of the cGAS-STING pathway. Mechanistically, we found that IIR downregulates mitochondrial transcription factor A (TFAM), which subsequently affects mtDNA stability, promoting the release of mtDNA into the cytoplasm and triggering the cGAS-STING pathway. Overexpression of TFAM stabilized mtDNA, reduced the accumulation of cytoplasmic mtDNA, inhibited cGAS-STING pathway activation, and alleviated cellular damage. Moreover, STING-deficient mice exhibited reduced inflammation, less tissue damage, and improved survival rates following IIR, highlighting the critical role of the STING pathway in IIR-induced injury. Our findings elucidate the close association between oxidative stress, inflammation, and cGAS-STING pathway activation in IIR. mtDNA leakage and TFAM downregulation are key mechanisms driving this activation. Importantly, TFAM plays a crucial role in stabilizing mtDNA and reducing mtDNA leakage during IIR. These results not only deepen our understanding of the molecular pathogenesis of IIR injury but also provide potential therapeutic strategies targeting the cGAS-STING pathway for treating IIR-related diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011142","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":"Effects of Troxerutin on Oxidative Stress, Inflammation and Galectin- 3 Expression in Intracerebroventricular Kainic Acid-Induced Neurotoxicity.","authors":"Mehmet Demir, Hulya Elbe, Dilan Cetinavci, Ercan Saruhan","doi":"10.1007/s10753-025-02301-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02301-9","url":null,"abstract":"<p><p>Excitotoxicity caused by excessive concentration of the excitatory neurotransmitter glutamate causes neuronal cell death and promotes neurodegenerative disorders. The neuroexcitant neurotoxin kainic acid (KA) induces excitotoxicity, leading to neuronal death via oxidative stress and inflammation, and its experimental use is widespread. This study was designed to determine the protective effect of Troxerutin (TXR) and its relationship with Galectin-3 (Gal-3) in experimental excitotoxicity with neuroinflammation and oxidative stress. Fifty male Wistar rats were divided into five groups (n = 10): Control group rats received intraperitoneal (ip) normal saline for 6 days. Sham group rats received a single dose of intracerebroventricular (icv) normal saline on the first day. KA group rats were treated with a single dose of KA; icv-0.5 μg/μl). TXR group rats treated with TXR for 6 days: ip-100 mg/kg) and KA + TXR group rats treated with KA (single dose) and TXR (6 days). It was observed that malondialdehyde (MDA) and interleukin-1β (IL-1β) levels increased and reduced glutathione (GSH) levels decreased in the cerebral cortex of rats with KA neurotoxicity. TXR treatment caused a significant improvement in MDA and GSH levels and a significant decrease in IL-1β levels in rats with the excitotoxicity model. Gal-3 expressions in the hippocampus and cerebellum increased in KA-treated rats, whereas TXR treatment decreased Gal-3 expressions. In addition, histopathological changes caused by KA administration showed improvement in TXR-treated groups. In conclusion, the findings showed that TXR treatment attenuated KA-induced neurotoxicity by reducing oxidative tissue damage, inflammatory response and Gal-3 expression.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965621","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}