ArticleJournal of neuroinflammation2017
Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke.
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 3 of them syntheses that pooled it.
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Who cites it
124 citing papers in PubMed, 3 syntheses or guidelines pooled it, 210 citations in OpenAlex.
- Homocysteine level at the acute stage of ischemic stroke as a biomarker of poststroke depression: A systematic review and meta-analysis.Frontiers in psychiatry · 2022Pooled it
- Identification of novel biomarkers in ischemic stroke: a genome-wide integrated analysis.BMC medical genetics · 2020Pooled it
- The association between homocysteine and ischemic stroke subtypes in Chinese: A meta-analysis.Medicine · 2020Pooled it
- HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation.Gut microbes · 2026Article
- Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.Current nutrition reports · 2026Review
- Integrated Transcriptomics and Machine Learning Reveal Lipid Metabolism Related Genes in Ischemic Stroke.Journal of molecular neuroscience : MN · 2026Article
- Mechanistic Study of S100A8-mediated Ferroptosis in Vascular Dementia Through the JAK2/STAT3 Pathway.Applied biochemistry and biotechnology · 2026Article
- Consumption of Cashew Nuts on Oxidative Stress and Neuroinflammation Markers in Methionine-Induced Hyperhomocysteinemia in Rats.Food science & nutrition · 2026Article
- Resibufogenin ameliorates cerebral ischemia-reperfusion injury by modulating microglial redox homeostasis via Keap1-Nrf2-TFR1/ARE axis.Acta pharmacologica Sinica · 2026Article
- IGF2BP1 Aggravates NLRP3 Inflammasome Activation and Pro-Inflammatory Phenotype in Microglia-like Cells by Promoting TRIM45 Expression.Neurotoxicity research · 2026Article
- Role and regulation of kinases in age-related macular degeneration.Journal of translational medicine · 2026Review
- HDAC1 dysregulation promotes pro-inflammatory microglial activation and aggravates post-stroke neuroinflammation.Annals of medicine · 2025Article
- Ferroptosis-associated transcriptional factors in neurological diseases: molecular mechanisms and therapeutic prospects.Experimental & molecular medicine · 2025Review
- Article
- Simultaneously infer cell pseudotime, velocity field, and gene interaction from multi-branch scRNA-seq data with scPN.NAR genomics and bioinformatics · 2025Article
- Study on the Efficacy and Pharmacological Mechanism of Innate Immune STING Pathway Regulators in the Treatment of Ischemic Brain Injury.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Role and Relationship Between Homocysteine and HMolecular neurobiology · 2025Review
- Exploring the shared genetic basis between autism spectrum disorder and gastrointestinal disorders: a bioinformatic study.Scientific reports · 2025Article
- STAT1 and STAT6 orchestrate Cbs transcription and transsulfur metabolism in microglia and contribute to parkinson's disease-related neuroinflammation.Cellular and molecular life sciences : CMLS · 2025Article
- Differential relationships among homocysteine levels, cognitive deficits, and low-frequency fluctuation in brain activity in bipolar disorder with suicidal ideation.BMC psychiatry · 2025Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundElevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.
methodsThe cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.
resultsElevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.
conclusionsSTAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.