ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Microglial Depletion with CSF1R Inhibitor During Chronic Phase of Experimental Traumatic Brain Injury Reduces Neurodegeneration and Neurological Deficits.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 1 of them a synthesis that pooled it.
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Who cites it
228 citing papers in PubMed, 1 synthesis or guideline pooled it, 334 citations in OpenAlex.
- Research progress on microglial pyroptosis and inflammasomes: a comprehensive analysis.Frontiers in aging neuroscience · 2025Pooled it
- P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics.Brain : a journal of neurology · 2026Article
- Matrix Rigidity Mechanoprimes Microglia for Inflammation Through Cytoskeletal-to-Nuclear Signaling and 3D Spatio-Epigenomic Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deep cerebellar stimulation restores chronic motor deficits and loss of GABAergic neurons following sensorimotor cortex surgical brain injury in female rats.Experimental neurology · 2026Article
- FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice.Nature communications · 2026Article
- A Long-Lived Human Neurovascular PENTA Culture Model Captures Incomplete Vascular Repair and Glia-Associated Signaling After Traumatic Brain Injury.Advanced healthcare materials · 2026Article
- Type I interferon signaling in microglia drives synaptic engulfment and neuronal loss following traumatic brain injury.Research square · 2026Article
- Repeated head impacts establish a senescent cranial bone marrow niche that impairs brain metabolism.Journal of neuroinflammation · 2026Article
- Microglial Ccl4-Ccr5 signaling links systemic inflammation to synaptic loss and memory deficits in chronic kidney disease.Journal of neuroinflammation · 2026Article
- Article
- PLX5622 did not alter anxiety-like behaviour and showed limited microglial depletion efficacy in a spinal cord injury model in female rats.Scientific reports · 2026Article
- The Arp2/3 complex is required for in situ haptotactic response of microglia to iC3b.EMBO reports · 2026Article
- Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.Science advances · 2026Article
- Mild Traumatic Brain Injury and Functional Amnesia: When Concussion Becomes a Gateway to Functional Cognitive Disorder.Brain sciences · 2026Review
- Microglial Lyn Kinase-TRPV4 axis mediates social deficits in a maternal immune activation model.Journal of neuroinflammation · 2026Article
- Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2026Article
- Inhibition of p38 MAPK after repetitive mTBI ameliorates immune signaling and functional deficits.Acta neuropathologica communications · 2026Article
- Repeated Mild Head Injury Establishes a Senescent Cranial Bone Marrow Niche that Impairs Brain Metabolism.bioRxiv : the preprint server for biology · 2026Article
- Novel Pyrazoline Derivatives as Therapeutic Candidate for Alzheimer's Disease: An Integrated Network Pharmacology and 3D-QSAR Modelling.Bioinformatics and biology insights · 2026Article
- Timed microglia depletion promotes functional network reorganization and motor recovery after stroke.Brain communications · 2026Article
168 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Chronic neuroinflammation with sustained microglial activation occurs following severe traumatic brain injury (TBI) and is believed to contribute to subsequent neurodegeneration and neurological deficits. Microglia, the primary innate immune cells in brain, are dependent on colony stimulating factor 1 receptor (CSF1R) signaling for their survival. In this preclinical study, we examined the effects of delayed depletion of chronically activated microglia on functional recovery and neurodegeneration up to 3 months postinjury. A CSF1R inhibitor, Plexxikon (PLX) 5622, was administered to adult male C57BL/6J mice at 1 month after controlled cortical impact to remove chronically activated microglia, and the inhibitor was withdrawn 1-week later to allow for microglial repopulation. Following TBI, the repopulated microglia displayed a ramified morphology similar to that of Sham uninjured mice, whereas microglia in vehicle-treated TBI mice showed the typical chronic posttraumatic hypertrophic morphology. PLX5622 treatment limited TBI-associated neuropathological changes at 3 months postinjury; these included a smaller cortical lesion, reduced hippocampal neuron cell death, and decreased NOX2- and NLRP3 inflammasome-associated neuroinflammation. Furthermore, delayed depletion of chronically activated microglia after TBI led to widespread changes in the cortical transcriptome and altered gene pathways involved in neuroinflammation, oxidative stress, and neuroplasticity. Using a variety of complementary neurobehavioral tests, PLX5622-treated TBI mice also had improved long-term motor and cognitive function recovery through 3 months postinjury. Together, these studies demonstrate that chronic phase removal of neurotoxic microglia after TBI using CSF1R inhibitors markedly reduce chronic neuroinflammation and associated neurodegeneration, as well as related motor and cognitive deficits.
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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.