ArticleJournal of neuroinflammation2023
Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
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- Human umbilical cord blood mononuclear cells ameliorate vascular dementia by modulating microglial myelin debris handling and white matter injury.Journal of neuroinflammation · 2026Article
- Physical exercise promotes white matter repair after ischemic stroke.Neural regeneration research · 2026Article
- IL-1β-mediated interaction between Müller cells and microglia through CXCL1/5-CXCR2 aggravates visual dysfunction in experimental glaucoma.Journal of neuroinflammation · 2026Article
- LCN2/SLC22A17 mediates the phagocytosis of GABAergic synapses by oligodendrocyte progenitor cells and contributes to cancer-induced pain and comorbid anxiety-like behaviors in mice.Acta neuropathologica communications · 2026Article
- FGF4 activates FGFR1 - PI3K/AKT signaling to enhance Clec10a-mediated intracellular myelin debris processing and promote spinal cord repair.Journal of neuroinflammation · 2026Article
- Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.Cellular & molecular biology letters · 2026Article
- Overexpression of PGRMC2 in astrocytes improved cognitive function in a mouse model of Alzheimer's disease by modulating neuroinflammation.Journal of translational medicine · 2026Article
- Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair.Acta pharmacologica Sinica · 2026Review
- AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition and Lipid Droplets Accumulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Oligodendrocyte: Development, Plasticity, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Neurovascular unit remodeling: focusing on glial cells in stroke injury and recovery.Frontiers in cellular neuroscience · 2026Review
- Targeting angiogenesis and white matter repair for enhanced functional recovery after acute ischemic stroke: A focus on the roles of glial cells.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Spatiotemporal patterns of gene expression changes in the mouse dentate gyrus following entorhinal denervation.Frontiers in molecular neuroscience · 2026Article
- Caveolin-1 Regulates Ultrastructural Alterations of Astrocytes in Chronic Cerebral Hypoperfusion.Inflammation · 2025Article
- TREML2 Modulates Microglial Phagocytosis of Myelin Debris via TLR9 in Chronic Cerebral Ischemia.Inflammation · 2025Article
- Cadmium-induced gut dysbiosis precedes the onset of hippocampus-dependent learning and memory deficits in mice.Toxicology · 2025Article
- Cellular Communication Networks Mediated by Microglia in Ischemic Stroke.CNS neuroscience & therapeutics · 2025Review
- Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.Diabetologia · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic cerebral ischemia induces white matter injury (WMI) contributing to cognitive decline. Both astrocytes and microglia play vital roles in the demyelination and remyelination processes, but the underlying mechanism remains unclear. This study aimed to explore the influence of the chemokine CXCL5 on WMI and cognitive decline in chronic cerebral ischemia and the underlying mechanism.
methodsBilateral carotid artery stenosis (BCAS) model was constructed to mimic chronic cerebral ischemia in 7-10 weeks old male mice. Astrocytic Cxcl5 conditional knockout (cKO) mice were constructed and mice with Cxcl5 overexpressing in astrocytes were generated by stereotactic injection of adeno-associated virus (AAV). WMI was evaluated by magnetic resonance imaging (MRI), electron microscopy, histological staining and western blotting. Cognitive function was examined by a series of neurobehavioral tests. The proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), phagocytosis of microglia were analyzed via immunofluorescence staining, western blotting or flow cytometry.
resultsCXCL5 was significantly elevated in the corpus callosum (CC) and serum in BCAS model, mainly expressed in astrocytes, and Cxcl5 cKO mice displayed improved WMI and cognitive performance. Recombinant CXCL5 (rCXCL5) had no direct effect on the proliferation and differentiation of OPCs in vitro. Astrocytic specific Cxcl5 overexpression aggravated WMI and cognitive decline induced by chronic cerebral ischemia, while microglia depletion counteracted this effect. Recombinant CXCL5 remarkably hindered microglial phagocytosis of myelin debris, which was rescued by inhibition of CXCL5 receptor C-X-C motif chemokine receptor 2 (CXCR2).
conclusionOur study revealed that astrocyte-derived CXCL5 aggravated WMI and cognitive decline by inhibiting microglial phagocytosis of myelin debris, suggesting a novel astrocyte-microglia circuit mediated by CXCL5-CXCR2 signaling in chronic 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 Socratic graph.