ArticleActa pharmacologica Sinica2025
VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives neuroinflammation in mouse ischemic stroke.
Article in Acta pharmacologica Sinica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed.
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Microglial Mitochondrial Dysfunction: The Storm Center of Post-Stroke Neuroinflammation.CNS neuroscience & therapeutics · 2026Review
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Ginsenoside Rg1 Ameliorates LPS-Induced Sepsis-Associated Lung Injury in Mice via VEGFC/D-VEGFR3 Signaling-Mediated Lymphangiogenesis and Lymphatic Remodeling.The Kaohsiung journal of medical sciences · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- Context-Dependent Regulation of Microglial Metabolic and Immune States via IL-3/CD123 Signaling: Implications for Glial Crosstalk and Cognitive Impairment.Molecular neurobiology · 2026Review
- Neuroinflammation after stroke: initiation, amplification and therapeutic prospects.Journal of translational medicine · 2026Review
- FOXA2 regulated by HDAC3-mediated deacetylation attenuates neuropathic pain by modulating microglial lipid metabolism and synaptic pruning dysregulation.Journal of neuroinflammation · 2025Article
- VEGFR-3 deficiency in astrocytes exacerbates Japanese encephalitis virus-induced neuroinflammation in mouse brains.Zoological research · 2025Article
- Fatty acid-binding protein 4 drives microglia-mediated neuroinflammation through promoting S100A9 expression and lipid droplet accumulation after intracerebral hemorrhage.Journal of neuroinflammation · 2025Article
- Inflammation associated microglial expansion disrupts hippocampal glial network communication, driving postoperative neurocognitive impairment.Journal of neuroinflammation · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocyte-derived IL-3 activates the corresponding receptor IL-3Rα in microglia. This cross-talk between astrocytes and microglia ameliorates the pathology of Alzheimer's disease in mice. In this study we investigated the role of IL-3/IL-3Rα cross-talk and its regulatory mechanisms in ischemic stroke. Ischemic stroke was induced in mice by intraluminal occlusion of the right middle cerebral artery (MCA) for 60 min followed by reperfusion (I/R). Human astrocytes or microglia subjected to oxygen-glucose deprivation and reoxygenation (OGD/Re) were used as in vitro models of brain ischemia. We showed that both I/R and OGD/Re significantly induced decreases in astrocytic IL-3 and microglial IL-3Rα protein levels, accompanied by pro-inflammatory activation of A1-type astrocytes and M1-type microglia. Importantly, astrocyte-derived VEGFD acting on VEGFR3 of astrocytes and microglia contributed to the cross-talk dysfunction and pro-inflammatory activation of the two glial cells, thereby mediating neuronal cell damage. By using metabolomics and multiple biochemical approaches, we demonstrated that IL-3 supplementation to microglia reversed OGD/Re-induced lipid metabolic reprogramming evidenced by upregulated expression of CPT1A, a rate-limiting enzyme for the mitochondrial β-oxidation, and increased levels of glycerophospholipids, the major components of cellular membranes, causing reduced accumulation of lipid droplets, thus reduced pro-inflammatory activation and necrosis, as well as increased phagocytosis of microglia. Notably, exogenous IL-3 and the VEGFR antagonist axitinib reestablished the cross-talk of IL-3/IL-3Rα, improving microglial lipid metabolic levels via upregulation of CPT1A, restoring microglial phagocytotic function and attenuating microglial pro-inflammatory activation, ultimately contributing to brain recovery from I/R insult. Our results demonstrate that VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives pro-inflammatory activation, causing lipid metabolic reprogramming of microglia. These insights suggest VEGFR3 antagonism or restoring IL-3 levels as a potential therapeutic strategy for ischemic stroke.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.