T cell receptor activation contributes to brain damage after intracerebral hemorrhage in mice

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 13, 2025

Our previous studies demonstrated that activated T cells accumulate in perihematomal regions following intracerebral hemorrhage (ICH) and exacerbate hemorrhagic brain injury. In the present study, we aimed to explore mechanisms underlying brain-infiltrating cell activation associated pathophysiological effects neurological outcomes ICH. We employed standardized collagenase injection-induced autologous blood injection models of ICH male C57BL/6J mice. receptor (TCR) activation, immune infiltration, cytokine production were quantified through immunostaining, flow cytometry, arrays at 1- 3-days post-ICH. Brain edema volume was measured 3 days post-ICH neurobehavioral assessments conducted up 14 Pharmacological inhibition TCR achieved using TCR-specific inhibitor AX-024, administered intraperitoneally a dosage 10 mg/kg 1-hour Flow cytometry immunostaining detected cells. Specific AX-024 administration markedly reduced pro-inflammatory cytokines Moreover, led significant reduction infiltration other leukocyte populations, significantly while improved long-term sensorimotor cognitive findings underscore critical role mobilization Inhibition via might be developed as promising therapeutic strategy improve However, further research is necessary thoroughly complex processes involved.

Language: Английский

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Research Progress on the Mechanism of Acupuncture Treatment for Sciatica

Journal of Contemporary Medical Practice, Journal Year: 2025, Volume and Issue: 7(2), P. 125 - 127

Published: Feb. 28, 2025

Sciatic neuralgia, a prevalent neuropathic pain condition, has been the focus of numerous clinical studies. Current treatment methods for sciatica encompass acupuncture, catgut embedding at acupoint, physical therapy and surgery. Among these, acupuncture demonstrated notable therapeutic efficacy, not only in alleviating symptoms but also effectively managing progression disease. Notably, exhibits low recurrence rate is characterised by high degree safety. The aim this paper to review research literature on mechanism treating home abroad recent years, summarise its from perspectives spinal cord, centre periphery, order provide theoretical basis sciatica.

Language: Английский

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Umbilical mesenchymal stem cells mitigate T-cell compartments shift and Th17/Treg imbalance in acute ischemic stroke via mitochondrial transfer

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 12, 2025

Acute ischemic stroke (AIS) initiates secondary injuries that worsen neurological damage and hinder recovery. While peripheral immune responses play a key role in outcomes, clinical results from immunotherapy have been suboptimal, with limited focus on T-cell dynamics. Umbilical mesenchymal stem cells (UMSCs) offer therapeutic potential due to their immunomodulatory properties. They can regulate reduce neuroinflammation, potentially enhancing recovery by fostering pro-regenerative environment. However, the effect of UMSCs dynamics AIS remains underexplored. This study investigates following examines how may mitigate dysregulation develop better treatment strategies. patients (NIHSS scores 0–15) were recruited within 72 h onset, blood samples collected Day 0 (enrollment) 7. compartments identified flow cytometry, plasma cytokine levels quantified using cytometric bead array (CBA). Mitochondria labeled MitoTracker. Peripheral mononuclear isolated, treated lipopolysaccharide (LPS), cocultured both direct contact Transwell systems. Flow CBA, RT-qPCR, immunofluorescence assays used detect compartments, gene expression markers for helper T (Th) cell differentiation, profiles, mitochondrial transfer, reactive oxygen species (ROS) production, membrane potential. Additionally, DNA was depleted. The effects mitochondria-depleted mice compared through behavioral assessments analysis microenvironment. In AIS, underwent phenotypic shift naïve effector or memory states, specific increase Th17 decrease regulatory cells, leading alterations T-cell-mediated functions. an ex vivo co-culture system, LPS stimulation further amplified these disparities, inducing dysfunction oxidative stress cells. Notably, restored function reversed transfer. Critically, UMSC significantly improved deficits disorders mice, whereas failed produce this effect. Our comprehensive insights into attributes acute mechanisms provide crucial theoretical foundation understanding treatment.

Language: Английский

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TREM2 Modulates Postoperative Cognitive Function in Aged Mice by Inhibiting the NLRP3/caspase-1 Pathway and Apoptosis via PLCγ2 Activation

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

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Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 16, 2025

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that remains incurable. Although the etiologies of ALS are diverse and precise pathogenic mechanisms not fully understood, approximately 20% cases caused by genetic factors. Therefore, advancing targeted gene therapies holds significant promise, at least for patients with etiologies. In this review, we summarize main strategies techniques current based on risk genes, review recent findings from animal studies clinical trials. Additionally, highlight ALS-related genes well-understood potential numerous emerging gene-targeted therapeutic approaches ALS.

Language: Английский

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Neuroinflammation and acute ischemic stroke: impact on translational research and clinical care

Frontiers in Surgery, Journal Year: 2025, Volume and Issue: 12

Published: April 28, 2025

Background Stroke, encompassing both ischemic and hemorrhagic subtypes, is a leading cause of mortality disability globally current treatments remain limited. Neuroinflammation plays crucial role in the pathophysiology stroke, influencing acute injury long-term recovery. Objective This review aims to provide comprehensive overview neuroinflammation detailing mechanisms, clinical implications, potential therapeutic strategies. Methods A detailed literature was conducted, focusing on recent advancements understanding neuroinflammatory processes including roles thromboinflammation, blood-brain barrier (BBB) disruption, immune response. Results The initial insult triggers an inflammatory cascade involving innate adaptive responses. BBB disruption allows peripheral cells neurotoxic substances infiltrate brain, exacerbating neuronal damage increasing risk infections such as pneumonia urinary tract infections. Thromboinflammation, characterized by platelet activation cell interactions, further complicates environment. Proteomic studies have identified key biomarkers that offer insights into mechanisms targets. Advances imaging techniques, PET MRI, enable real-time monitoring neuroinflammation, facilitating personalized treatment approaches. Conclusion significantly impacts stroke outcomes, presenting challenges opportunities for treatment. Current immunologic strategies are Future research should aim elucidate complex interactions refine use, develop effective interventions mitigate neuroinflammation.

Language: Английский

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The impact of inflammation and iron metabolism on gene expression alterations in ischemic stroke: a bioinformatics approach

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 30, 2025

This study explores the differential expression of inflammation and iron metabolism-related genes (IIMRDEGs) in Ischemic Stroke (IS), a major contributor to global morbidity mortality. Using Gene Expression Omnibus (GEO) query tool, we integrated gene datasets GSE22255 GSE16561. We identified 56 differentially expressed (DEGs), including 42 that were upregulated 14 downregulated, according criteria |logFC| > 0.5 p < 0.05. An intersection with known IIMRDEGs revealed 16 significant relevance IS, such as SLC22A4 DUSP1. Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses indicated these are mainly involved leukocyte chemotaxis responses bacterial molecules, addition IL-17 TNF signaling pathways. A protein-protein interaction (PPI) network 12 8 hub genes, IL7R ADM, which exhibited differences (p 0.001) potential diagnostic utility AUC values between 0.7 0.9 ROC curve analysis. Furthermore, immune infiltration analysis showed notable 7 cell types IS control samples. Our findings advance understanding ischemic stroke mechanisms present biomarkers for improving diagnosis therapeutic strategies.

Language: Английский

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Employ machine learning to identify NAD+ metabolism-related diagnostic markers for ischemic stroke and develop a diagnostic model

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 196, P. 112584 - 112584

Published: Sept. 19, 2024

Language: Английский

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The impact of maternal anti-inflammatory drugs on surgical anesthesia-induced neuroinflammation and cognitive impairment in offspring mice

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 8, 2024

Background The impact of maternal surgery combined with general anesthesia on neuroinflammation and the development learning memory impairment in offspring remains unclear. This study utilized a pathogen-free laparotomy model to investigate these changes during second trimester, as well their response anti-inflammatory therapy. Methods C57BL/6 pregnant mice at 14.5-day embryo stage (E 14.5) were either exposed sevoflurane alone or underwent procedure. neuroinflammatory was evaluated 7, 14, 21, 28 days postnatal (P7, P14, P21, P28). Tau phosphorylation cognitive ability assessed P28 P30, respectively. perioperative administration ibuprofen (60 mg/kg) aforementioned subsequently evaluated. Results In group, levels inflammatory factors (IL-4, IL-8, IL-17A, TGF-β, M-CSF, CCL2) brains mice, including cerebral cortex hippocampus, remained consistently elevated from P7 P28. At while majority cytokine has no statistical difference, there still significant reactivation cytokines observed frontal hippocampus Furthermore, abnormal tau deficits P30. Administration led improvements performance, reduction systemic inflammation, inhibiting hippocampus. Conclusion Our findings indicate that dysfunction is correlated phosphorylation. Cognitive after can persist least until Anti-inflammatory medications have been shown enhance function by rapidly reducing inflammation brain, also impacting neurological changes. discovery may implications for treatment strategies aimed managing post-operative patients.

Language: Английский

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Assessment of corticospinal tract damage and cytokines response in early and late stages of acute unilateral brainstem infarction patients

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 29, 2024

Acute brainstem infarction is associated with high morbidity and mortality, the integrity of corticospinal tract (CST) detected via diffusion tensor imaging (DTI) can assist in predicting motor recovery patients. In addition to damage caused by ischemia reperfusion, sterile inflammation also contributes brain injury after stroke. However, changes CST DTI acute have yet be fully elucidated, it still unclear whether cause CST.

Language: Английский

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