ArticleFrontiers in immunology2023
Limitations of PLX3397 as a microglial investigational tool: peripheral and off-target effects dictate the response to inflammation.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2026Pooled it
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Glial heterogeneity shapes region-specific angiogenesis and neurovascular integrity in the CNS.Science advances · 2026Article
- Article
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- TMEM119+ microglia MHC class I restricted antigen presentation impacts CD8 T cell memory, effector status, and blood-brain barrier disruption during neurotropic virus infection.Research square · 2026Article
- Enhancing the specificity of microglia genetic targeting using a CSF1R inhibitor.Cell reports · 2026Article
- Immunity in Rodent Models of Stress.Biological psychiatry · 2026Review
- Sex-Dependent Effects of CSF1R-Mediated Myeloid Cell Depletion in a Mouse Model of Multiple System Atrophy.The European journal of neuroscience · 2026Article
- Ginsenoside Rg2 attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3-mediated pyroptosis.Journal of neuroinflammation · 2026Article
- Targeting microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and therapeutic approaches.Frontiers in immunology · 2026Review
- Microglia depletion improves hippocampal circuit function after mild traumatic brain injury in male mice.Brain, behavior, and immunity · 2026Article
- CSF1R and IL1R1 inhibitors synergistically attenuate the early pathogenesis of traumatic brain injury in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Neonatal microglia replacement in mice modulates seizure severity in adulthood.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Neuroinflammation in an Optimized Model of Lysophosphatidic Acid (LPA)-Induced Post-hemorrhagic Hydrocephalus.Neurochemical research · 2025Article
- Dual-targeting CSF1R signaling attenuates neurotoxic myeloid activation and preserves photoreceptors in retinitis pigmentosa.Journal of neuroinflammation · 2025Article
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
- The Influence of Changes in Microglia Development on the Plasticity of the Developing Visual Cortex Circuit in Juvenile Mice.Investigative ophthalmology & visual science · 2025Article
- Is the Relationship Between Adolescent Social Isolation and Anxiety-Like Behaviors Altered by Microglia Ablation in Female Long Evans Rats?Brain and behavior · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microglia, the resident macrophages of the central nervous system (CNS), play a critical role in CNS homeostasis and neuroinflammation. Pexidartinib (PLX3397), a colony-stimulating factor 1 (CSF1) receptor inhibitor, is widely used to deplete microglia, offering flexible options for both long-term depletion and highly versatile depletion-repopulation cycles. However, the potential impact of PLX3397 on peripheral (immune) cells remains controversial. Until now, the microglia-specificity of this type of compounds has not been thoroughly evaluated, particularly in the context of peripherally derived neuroinflammation. Our study addresses this gap by examining the effects of PLX3397 on immune cells in the brain, liver, circulation and bone marrow, both in homeostasis and systemic inflammation models. Intriguingly, we demonstrate that PLX3397 treatment not only influences the levels of tissue-resident macrophages, but also affects circulating and bone marrow immune cells beyond the mononuclear phagocyte system (MPS). These alterations in peripheral immune cells disrupt the response to systemic inflammation, consequently impacting the phenotype irrespective of microglial depletion. Furthermore, we observed that a lower dose of PLX3397, which does not deplete microglia, demonstrates similar (non-)MPS effects, both in the periphery and the brain, but fails to fully replicate the peripheral alterations seen in the higher doses, questioning lower doses as a 'peripheral control' strategy. Overall, our data highlight the need for caution when interpreting studies employing this compound, as it may not be suitable for specific investigation of microglial function in the presence of systemic inflammation.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.