ArticlePloS one2018
CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral ischemia.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
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- Wild-Type TP53 Predicts Poor Prognosis in Lower-Grade Glioma via TP53-CXCL14-GATA3 Axis.Journal of molecular neuroscience : MN · 2025Article
- Immune-mediated blood-brain barrier disruption after ischemic stroke: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
- The Multifaceted Nature of Macrophages in Cardiovascular Disease.Biomedicines · 2024Review
- The Roles of RhoA/ROCK/NF-κB Pathway in Microglia Polarization Following Ischemic Stroke.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- Sodium Tanshinone IIA Sulfonate Ameliorates Oxygen-glucose Deprivation/Reoxygenation-induced Neuronal Injury via Protection of Mitochondria and Promotion of Autophagy.Neurochemical research · 2023Article
- Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments.The Journal of clinical investigation · 2023Observational
- S100B Affects Gut Microbiota Biodiversity.International journal of molecular sciences · 2023Article
- Microglia as the Critical Regulators of Neuroprotection and Functional Recovery in Cerebral Ischemia.Cellular and molecular neurobiology · 2022Review
- Effects of intraperitoneal injection of lipopolysaccharide-induced peripheral inflammation on dopamine neuron damage in rat midbrain.CNS neuroscience & therapeutics · 2022Article
- Dimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation.EJNMMI research · 2022Article
- MORPHIOUS: an unsupervised machine learning workflow to detect the activation of microglia and astrocytes.Journal of neuroinflammation · 2022Article
- Microglia subtypes show substrate- and time-dependent phagocytosis preferences and phenotype plasticity.Frontiers in immunology · 2022Article
- Host Immunity Influences the Composition of Murine Gut Microbiota.Frontiers in immunology · 2022Article
- Grafted human ESC-derived astroglia repair spinal cord injury via activation of host anti-inflammatory microglia in the lesion area.Theranostics · 2022Article
- Modulating poststroke inflammatory mechanisms: Novel aspects of mesenchymal stem cells, extracellular vesicles and microglia.World journal of stem cells · 2021Review
- CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway.Inflammation · 2021Article
- Characterization of Immune Cell Subsets of Tumor Infiltrating Lymphocytes in Brain Metastases.Biology · 2021Article
- Microglial/Macrophage polarization and function in brain injury and repair after stroke.CNS neuroscience & therapeutics · 2021Review
- Microglial Polarization: Novel Therapeutic Strategy against Ischemic Stroke.Aging and disease · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke. Comparing key receptors involved in M1 polarization (CD8, IFNγR, Clec4, FcγR, TLR3 and TLR4) and their signal transducers (Syk, Stat1, Irf3, and Traf6) at the day 4 time point, we showed a strong upregulation of CD8 along with SYK transducer in dissected perilesional brain tissue. We further showed that CD8 expression in the post-stroke brain was associated with activated (CD68+) macrophages and that progressive accumulation of CD8+CD68+ cells in the post-stroke brain coincided with increased iNOS (M1 marker) and reduced Arg1 (M2 marker) expression on these cells. In vitro ligand-based stimulation of the CD8 receptor caused increased iNOS expression and an enhanced capacity to phagocytose E. coli particles; and interestingly, CD8 stimulation was also able to repolarize IL4-treated M2 cells to an M1 phenotype. Our data suggest that increased CD8 signaling in the post-stroke brain is primarily associated with microglia/macrophages and can independently drive M1 polarization, and that modulation of CD8 signaling could be a potential target to limit secondary post-stroke brain damage.
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Registered trials
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.