ArticleFrontiers in immunology2023
Interferon-β modulates microglial polarization to ameliorate delayed tPA-exacerbated brain injury in ischemic stroke.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 11 citations in OpenAlex.
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- Case Report: Lung transplantation for rare anti-MDA5-positive rapidly progressive interstitial lung disease: two cases and a narrative review.Frontiers in immunology · 2026Review
- The multi-target protective effects of quercetin in cerebrovascular diseases: a dietary strategy for endothelial repair and neuroprotection.Frontiers in nutrition · 2026Review
- AD16 Modulates Microglial Activation and Polarization to Mitigate Neuroinflammation in Ischemic Stroke Models Through α7nAChR-ERK-STAT3 Signaling.CNS neuroscience & therapeutics · 2025Article
- Type I Interferon Signalling and Ischemic Stroke: Mechanisms and Therapeutic Potentials.Translational stroke research · 2025Review
- Macrophage-Derived Type 1 IFN, Renal Tubular Epithelial Cell Polyploidization, and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2025Article
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- Systems-level computational modeling in ischemic stroke: from cells to patients.Frontiers in physiology · 2024Review
- Ischemia-induced endogenous Nrf2/HO-1 axis activation modulates microglial polarization and restrains ischemic brain injury.Frontiers in immunology · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue plasminogen activator (tPA) is the only FDA-approved drug for the treatment of ischemic stroke. Delayed tPA administration is associated with increased risks of blood-brain barrier (BBB) disruption and hemorrhagic transformation. Studies have shown that interferon beta (IFNβ) or type I IFN receptor (IFNAR1) signaling confers protection against ischemic stroke in preclinical models. In addition, we have previously demonstrated that IFNβ can be co-administered with tPA to alleviate delayed tPA-induced adverse effects in ischemic stroke. In this study, we investigated the time limit of IFNβ treatment on the extension of tPA therapeutic window and assessed the effect of IFNβ on modulating microglia (MG) phenotypes in ischemic stroke with delayed tPA treatment. Mice were subjected to 40 minutes transient middle cerebral artery occlusion (MCAO) followed by delayed tPA treatment in the presence or absence of IFNβ at 3h, 4.5h or 6h post-reperfusion. In addition, mice with MG-specific IFNAR1 knockdown were generated to validate the effects of IFNβ on modulating MG phenotypes, ameliorating brain injury, and lessening BBB disruption in delayed tPA-treated MCAO mice. Our results showed that IFNβ extended tPA therapeutic window to 4.5h post-reperfusion in MCAO mice, and that was accompanied with attenuated brain injury and lessened BBB disruption. Mechanistically, our findings revealed that IFNβ modulated MG polarization, leading to the suppression of inflammatory MG and the promotion of anti-inflammatory MG, in delayed tPA-treated MCAO mice. Notably, these effects were abolished in MG-specific IFNAR1 knockdown MCAO mice. Furthermore, the protective effect of IFNβ on the amelioration of delayed tPA-exacerbated ischemic brain injury was also abolished in these mice. Finally, we identified that IFNβ-mediated modulation of MG phenotypes played a role in maintaining BBB integrity, because the knockdown of IFNAR1 in MG partly reversed the protective effect of IFNβ on lessening BBB disruption in delayed tPA-treated MCAO mice. In summary, our study reveals a novel function of IFNβ in modulating MG phenotypes, and that may subsequently confer protection against delayed tPA-exacerbated brain injury in ischemic stroke.
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