ArticleJournal of neuroinflammation2021
Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 263 citations in OpenAlex.
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- Histidine metabolic reprogramming drives oxidative stress induced mtDNA release to promote necroptosis and airway inflammation in severe asthma.Redox biology · 2026Article
- Reprogramming pulmonary B cells by ANXA1 silencing halts lung metastatic niche formation in breast cancer.Journal of nanobiotechnology · 2026Article
- Tanshinone IIA Inhibits Microglial Activation and Inflammation and Relieves Cerebral Ischemia‒Reperfusion Injury Through TGM2/PANX1.Biochemical genetics · 2026Article
- FPR2/ALX stimulation modulates microglia and natural killer cells to restrict autoimmune astrocytopathy.Acta pharmacologica Sinica · 2026Article
- Regulation of acute myocardial infarction by CircTMCC1 through mitochondrial dysfunction and AMPK/mTOR-driven M1 macrophage polarization: role in QFR assessment.Cell death discovery · 2026Article
- Vespakinin-M delineates an AMPK/mTOR-arginine-TCA cycle axis to act as an immunometabolic switch in post-stroke microglia.Redox biology · 2026Article
- Targeting SLK protects against cerebral ischemia-reperfusion injury by regulating USP8-mediated HIF-1α stabilization and RhoA/ROCK activation.Cellular & molecular biology letters · 2026Article
- Chemerin 15 peptide reduces neuroinflammation via the ChemR23 receptor after ischemia-reperfusion injury.Neural regeneration research · 2026Article
- Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.Nature communications · 2026Article
- Ginsenoside Rb2 alleviates myocardial ischemia/reperfusion injury through IKKα lactylation regulation of macrophage polarization.Cardiovascular diagnosis and therapy · 2026Article
- Annexin A1 in Alzheimer's disease: A new therapeutic strategy focusing on neuroinflammation.Neural regeneration research · 2026Article
- Exercise Improves Mitochondrial Homeostasis: A Potential Neuroprotective Strategy for Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2026Review
- Polydatin Inhibits Neuroinflammation in Cerebral Ischemia-Reperfusion Injury Through Suppressing the CXCL3/CXCR2 Axis.CNS neuroscience & therapeutics · 2026Article
- Tumour-derived SAA1 reprogrammes macrophages to promote CXCL1-mediated metastasis in Ovarian Cancer.Clinical and translational medicine · 2026Article
- Targeting microglial PANoptosis through AMPK activation: Metformin as a promising therapy for spinal cord injury.Journal of pharmaceutical analysis · 2026Article
- Propofol upregulates MFG‑E8 in BV2 cells to inhibit pyroptosis mediated by the NF‑κB/NLRP3 pathway, thereby ameliorating ischemic‑reperfusion neuronal injury.International journal of molecular medicine · 2026Article
- [Mechanisms of gutZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundCerebral ischemia-reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated.
methodsWe retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen-glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization.
resultsThe baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2-3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood-brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments.
conclusionsAc2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.
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