ArticleFrontiers in cellular neuroscience2020
Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Aggravates the Progression of Cerebral Ischemic Pathology.
Article in Frontiers in cellular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Sunitinib attenuates secondary injury via the regulation of peri-hematomal microglia at the acute phase of intracerebral hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Multicolor fate mapping of microglia reveals polyclonal proliferation, heterogeneity, and cell-cell interactions after ischemic stroke in mice.Nature communications · 2025Article
- Changes in Neuroimmunological Synapses During Cerebral Ischemia.Translational stroke research · 2025Review
- Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond.Journal of neuroimmunology · 2025Review
- Electroacupuncture Preconditioning Ameliorates the Ischemic Microenvironment to Improve Long-Term Potentiation in Chronic Cerebral Hypoperfusion Rats With MGE Neural Progenitor Transplantation.Neural plasticity · 2025Article
- Rapamycin Alleviates Neuronal Injury and Modulates Microglial Activation After Cerebral Ischemia.Molecular neurobiology · 2024Article
- An adapted protocol to derive microglia from stem cells and its application in the study of CSF1R-related disorders.Molecular neurodegeneration · 2024Article
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- From static to dynamic: live observation of the support system after ischemic stroke by two photon-excited fluorescence laser-scanning microscopy.Neural regeneration research · 2023Review
- Spatio-Temporal Characterization of Brain Inflammation in a Non-human Primate Stroke Model Mimicking Endovascular Thrombectomy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.Biomolecules · 2023Review
- Microglia dynamic response and phenotype heterogeneity in neural regeneration following hypoxic-ischemic brain injury.Frontiers in immunology · 2023Review
- Immune dynamics in the CNS and its barriers during homeostasis and disease.Immunological reviews · 2022Review
- Microglia-mediated neuroinflammation and neuroplasticity after stroke.Frontiers in cellular neuroscience · 2022Review
- Glial functions in the blood-brain communication at the circumventricular organs.Frontiers in neuroscience · 2022Review
- Colony stimulating factors in the nervous system.Seminars in immunology · 2021Review
- Treatment With the CSF1R Antagonist GW2580, Sensitizes Microglia to Reactive Oxygen Species.Frontiers in immunology · 2021Article
- Immunoresponsive gene 1 modulates the severity of brain injury in cerebral ischaemia.Brain communications · 2021Article
- Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates.Theranostics · 2021Article
- New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery.Frontiers in cellular neuroscience · 2021Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemic stroke can induce rapid activation of the microglia. It has been reported that the microglia's survival is dependent on colony-stimulating factor 1 receptor (CSF1R) signaling and that pharmacological inhibition of CSF1R leads to morphological changes in the microglia in the healthy brain. However, the impact of CSF1R inhibition on neuronal structures and motor ability after ischemia-reperfusion remains unclear. In this study, we investigated microglial de-ramification, proliferation, and activation after inhibition of CSF1R by a tyrosine kinase inhibitor (ki20227) in a mouse model of global cerebral ischemia induced by bilateral common carotid artery ligation (BCAL). In addition to microglial morphology, we evaluated the mRNA expression of cytokines, chemokines, and inflammatory receptors. Our results show that pharmacological inhibition of CSF1R in ischemic mice resulted in the blockade of microglial proliferation and a shift in microglial morphology reflected by excessive de-ramification and a more activated phenotype accompanied by an enhanced innate immune response. Furthermore, we show that pharmacological inhibition of CSF1R in ischemic mice resulted in the aggravation of neuronal degeneration and behavioral impairment. Intravital two-photon imaging revealed that although pharmacological inhibition of CSF1R did not affect the recovery of dendritic structures, it caused a significant increase in spine elimination during reperfusion in ischemic mice. These findings suggest that pharmacological inhibition of CSF1R induces a blockade of microglial proliferation and causes acute activation of the microglia accompanied by a severe inflammatory response. It aggravates neuronal degeneration, loss of dendritic spines, and behavioral deficits after transient global cerebral ischemia.
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