ArticleCNS neuroscience & therapeutics2019
Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway.
Article in CNS neuroscience & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Usage, anti-inflammatory effect and safety of adjunctive acupuncture for cerebral infarction: an Apriori algorithm-based data mining and meta-analysis.Frontiers in neurology · 2025Pooled it
- Recent Advances in Molecular Research on Hydrogen Sulfide (HInternational journal of molecular sciences · 2022Pooled it
- Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic/Rehabilitative Interventions in Acute Ischemic Stroke.International journal of molecular sciences · 2022Pooled it
- Melatonin promotes recovery from ischemic stroke by modulating microglia polarization and inhibiting oligodendrocyte pyroptosis via the RORα/AMPKα/STAT1 pathway.Journal of translational medicine · 2026Article
- LIF and Oncostatin M mitigate LPS-induced acute endometritis via distinct immunoregulatory mechanisms in peritoneal macrophagesiScience · 2026Article
- Nanomedicines and stroke: Advantages in chronic inflammation treatment and neural regeneration.Neural regeneration research · 2026Article
- Mechanistic insights into the neuroprotective effects of yangyin formula on cerebral ischemia-reperfusion injury via the IL-17A/MAPK/NF-κB signaling pathway.Journal of molecular histology · 2026Article
- Restricting Synaptotagmin-3 Internalization Mitigates Cerebral Ischemia/Reperfusion Injury by Curtailed Neuronal Apoptosis and Microglial Re-Programming.CNS neuroscience & therapeutics · 2026Article
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- NLRP3-mediated pyroptosis in cardiovascular disease: from molecular mechanisms to therapeutic targets.Frontiers in pharmacology · 2026Review
- Microglial TIA1-mediated stress granules promote neuroinflammation and aggravate neuron loss in mice after ischemic stroke by inhibiting IGF2 signaling.Theranostics · 2026Article
- Cell membrane-coated nanoparticles against non-alcoholic fatty liver disease via regulating endoplasmic reticulum stress.Regenerative biomaterials · 2026Article
- Melatonin Attenuates the Inflammatory Response of Astrocyte Following Ischemia Stroke through SIRT1/NF-κΒ Signaling Pathway.Molecular neurobiology · 2025Article
- Identification of Key Ferroptosis-Related Genes as Potential Diagnostic Biomarkers for Ischemic Stroke: Evidences from Integrated Bioinformatics Analysis and Experiments.Cellular and molecular neurobiology · 2025Article
- Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation.Stroke and vascular neurology · 2025Article
- Geniposide protects against cerebral ischemic injury by targeting SOX2/RIPK1 axis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- IFITM1 promotes microglial polarization and NLRP3 inflammasome activation in ischemic stroke through up-regulating c-FOS.Cytotechnology · 2025Article
- AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through α7nAChR-ERK-STAT3 Signaling.CNS neuroscience & therapeutics · 2025Article
- The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology.Antioxidants (Basel, Switzerland) · 2025Review
- Melatonin Promotes B-Cell Maturation and Attenuates Post-Ischemic Immunodeficiency in a Murine Model of Transient Focal Cerebral Ischemia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMicroglia and infiltrated macrophages play important roles in inflammatory processes after ischemic stroke. Modulating microglia/macrophage polarization from pro-inflammatory phenotype to anti-inflammatory state has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. Melatonin has been shown to be neuroprotective in experimental stroke models. However, the effect of melatonin on microglia polarization after stroke and underlying mechanisms remain unknown.
methodsIn vivo, cerebral ischemia was induced by distal middle cerebral artery occlusion (dMCAO) in C57BL/6J mice. Melatonin was injected intraperitoneally (20 mg/kg) at 0 and 24 hours after ischemia. In vitro, the microglial cell line BV2 was stimulated to the pro-inflammatory state with conditioned media (CM) collected from oxygen-glucose deprivation (OGD) challenged neuronal cell line Neuro-2a (N2a). Real-time PCR was utilized to detect the mRNA expression of microglia phenotype markers. Activation of signal transducer and activator of transcription 3 (STAT3) pathway was determined by Western blot of phosphorylated STAT3 (pSTAT3). A neuron-microglia co-culture system was used to determine whether melatonin can inhibit the neurotoxic effect of pro-inflammatory microglia to post-OGD neurons.
resultsMelatonin treatment reduced brain infarct and improved neurological functions 3 days after dMCAO, which was accompanied by decreased expression of pro-inflammatory markers and increased expression of anti-inflammatory markers in the ischemic brain. In vitro studies confirmed that melatonin directly inhibited the pro-inflammatory responses in BV2 cells upon exposure to OGD neuron CM. The microglia possessing pro-inflammatory phenotype exacerbated post-OGD N2a cells death, whereas melatonin reduced such neurotoxic effect. Further, melatonin enhanced the otherwise inhibited pSTAT3 expression in BV2 cells treated with OGD neuron CM. STAT3 blockade significantly reduced the effect of melatonin on microglial phenotype shift.
conclusionMelatonin treatment ameliorates brain damage at least partially through shifting microglia phenotype from pro-inflammatory to anti-inflammatory polarity in a STAT3-dependent manner.
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