ArticleJournal of neuroinflammation2016
Class I PI3K inhibitor ZSTK474 mediates a shift in microglial/macrophage phenotype and inhibits inflammatory response in mice with cerebral ischemia/reperfusion injury.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Chemerin 15 peptide reduces neuroinflammation via the ChemR23 receptor after ischemia-reperfusion injury.Neural regeneration research · 2026Article
- Article
- Myricetin improves apoptosis after ischemic stroke via inhibiting MAPK-ERK pathway.Molecular biology reports · 2023Article
- Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder.Current neuropharmacology · 2022Review
- Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic neuroinflammation.Journal of neuroinflammation · 2021Review
- Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway.Journal of neuroinflammation · 2021Article
- Bioengineering CXCR4-overexpressing cell membrane functionalized ROS-responsive nanotherapeutics for targeting cerebral ischemia-reperfusion injury.Theranostics · 2021Article
- Autophagy and inflammation in ischemic stroke.Neural regeneration research · 2020Review
- Microglia Mediated Neuroinflammation: Focus on PI3K Modulation.Biomolecules · 2020Review
- Electroacupuncture Ameliorates Cerebral I/R-Induced Inflammation through DOR-BDNF/TrkB Pathway.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- S1PBiomolecules & therapeutics · 2019Article
- Acacetin protects against cerebral ischemia-reperfusion injuryNeural regeneration research · 2019Article
- Different Approaches to Modulation of Microglia Phenotypes After Spinal Cord Injury.Frontiers in systems neuroscience · 2019Review
- PI3K Signaling in Neurons: A Central Node for the Control of Multiple Functions.International journal of molecular sciences · 2018Review
- Humanin analogue, S14G-humanin, has neuroprotective effects against oxygen glucose deprivation/reoxygenation by reactivating Jak2/Stat3 signaling through the PI3K/AKT pathway.Experimental and therapeutic medicine · 2017Article
- Influenza virus replication in macrophages: balancing protection and pathogenesis.The Journal of general virology · 2017Review
- Delayed decompression exacerbates ischemia-reperfusion injury in cervical compressive myelopathy.JCI insight · 2017Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroglia/macrophages play a critical role in the inflammatory and immune processes of cerebral ischemia/reperfusion injury. Since microglia/macrophages can reversibly shift their phenotype toward either a "detrimental" or a "restorative" state in the injured central nervous system (CNS), compounds mediate that shift which could inhibit inflammation and restore the ability to alleviate cerebral ischemia/reperfusion injury would have therapeutic potential.
methodsTransient middle cerebral artery occlusion was induced in male C57BL/6 mice. Mice were randomly separated into a sham-operated group, a control group, and a ZSTK474-treated group. We investigated the effect of ZSTK474 by assessing neurological deficits, infarct volume, and histopathological changes. We then determined the potential mechanism by immunofluorescent staining, quantitative real-time polymerase chain reaction (PCR), and Western blot analysis. The Tukey's test or Mann-Whitney U test was used to compare differences among the groups.
resultsZSTK474 alleviated neurological deficits and reduced infarct volume in the cerebral ischemia/reperfusion injury model. Presumably, ZSTK474 shifted the phenotype of microglia/macrophages to a restorative state, since this treatment decreased the secretion of pro-inflammatory factors and advanced the secretion of anti-inflammatory factors. These neuroprotective properties of ZSTK474 may be mediated by the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway.
conclusionsZSTK474 can mediate a shift in microglia/macrophage phenotype and inhibit the inflammatory response in cerebral ischemia reperfusion injury of mice. These effects appeared to ensue via the PI3K/AKT/mTORC1 pathway. Therefore, ZSTK474 may represent a therapeutic intervention with potential for circumventing the catastrophic aftermath of ischemic stroke.
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