ArticleAging2022
Regulation of microglial activation in stroke in aged mice: a translational study.
Article in Aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Heme Oxygenase-1 Contributes to Dampening Proinflammatory Activation in the Human Microglial Cell Line HMC3 and Controls the Transcription Factor IRF5.Biomolecules · 2026Article
- Targeting the Biology of Aging in Cerebrovascular Disease: Inflammation, Metabolism, Senescence, and Regeneration.International journal of molecular sciences · 2026Review
- Peripheral CD200R signaling: A critical regulator of post-stroke inflammation in aged mice.Brain research bulletin · 2026Article
- Escape of Kdm6a from X Chromosome Is Detrimental to Ischemic Brains via IRF5 Signaling.Translational stroke research · 2025Article
- Progesterone Receptor Agonist, Nestorone, Exerts Long-Term Neuroprotective Effects Against Permanent Focal Cerebral Ischemia in Adult and Aged Male Rats.Translational stroke research · 2025Article
- Natural polyphenol mangiferin delays neuronal cell senescence by inhibiting neuroinflammation mediated by microglial activation.IBRO neuroscience reports · 2025Article
- The Aging Immune System: A Critical Attack on Ischemic Stroke.Molecular neurobiology · 2025Review
- Profiling X chromosome genes expression relevant to sex dimorphism in stroke: insights from transcriptomics landscape analysis.Frontiers in genetics · 2025Article
- Uncovering a new mechanism of ischemic stroke: a study of the association between γδ T cells and immunoinflammation.Frontiers in immunology · 2025Review
- Mechanisms Underlying Vascular Inflammaging: Current Insights and Potential Treatment Approaches.Aging and disease · 2024Review
- Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling.Research square · 2024Article
- Advancing Post-Stroke Depression Research: Insights from Murine Models and Behavioral Analyses.Life (Basel, Switzerland) · 2024Review
- Central IRF4/5 Signaling Are Critical for Microglial Activation and Impact on Stroke Outcomes.Translational stroke research · 2024Article
- Astrocyte-Derived Extracellular Vesicles for Ischemic Stroke: Therapeutic Potential and Prospective.Aging and disease · 2024Review
- Physical exercise regulates microglia in health and disease.Frontiers in neuroscience · 2024Review
- Updates of the role of B-cells in ischemic stroke.Frontiers in cellular neuroscience · 2024Review
- Possible Implications of Obesity-Primed Microglia that Could Contribute to Stroke-Associated Damage.Cellular and molecular neurobiology · 2023Review
- The mechanism of microglia-mediated immune inflammation in ischemic stroke and the role of natural botanical components in regulating microglia: A review.Frontiers in immunology · 2022Review
- Progress of research into microglial mediation of central post-stroke pain.International journal of immunopathology and pharmacologyReview
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Numerous neurochemical changes occur with aging and stroke mainly affects the elderly. Our previous study has found interferon regulatory factor 5 (IRF5) and 4 (IRF4) regulate neuroinflammation in young stroke mice. However, whether the IRF5-IRF4 regulatory axis has the same effect in aged brains is not known. In this study, aged (18-20-month-old), microglial IRF5 or IRF4 conditional knockout (CKO) mice were subjected to a 60-min middle cerebral artery occlusion (MCAO). Stroke outcomes were quantified at 3d after MCAO. Flow cytometry and ELISA were performed to evaluate microglial activation and immune responses. We found aged microglia express higher levels of IRF5 and lower levels of IRF4 than young microglia after stroke. IRF5 CKO aged mice had improved stroke outcomes; whereas worse outcomes were seen in IRF4 CKO vs. their flox controls. IRF5 CKO aged microglia had significantly lower levels of IL-1β and CD68 than controls; whereas significantly higher levels of IL-1β and TNF-α were seen in IRF4 CKO vs. control microglia. Plasma levels of TNF-α and MIP-1α were decreased in IRF5 CKO vs. flox aged mice, and IL-1β/IL-6 levels were increased in IRF4 CKO vs. controls. The anti-inflammatory cytokines (IL-4/IL-10) levels were higher in IRF5 CKO, and lower in IRF4 CKO aged mice vs. their flox controls. IRF5 and IRF4 signaling drives microglial pro- and anti-inflammatory response respectively; microglial IRF5 is detrimental and IRF4 beneficial for aged mice in stroke. IRF5-IRF4 axis is a promising target for developing new, effective therapeutic strategies for the cerebral ischemia.
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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.