ArticleJournal of neuroinflammation2022
Pentoxifylline alleviates ischemic white matter injury through up-regulating Mertk-mediated myelin clearance.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- A bibliometric analysis of research on cognitive function and carotid atherosclerosis: global trends and hotspots.Frontiers in neurology · 2025Pooled it
- Astrocytic NLRP3 cKO Mitigates Cognitive Impairment Induced by Paclitaxel in Mice.Neurochemical research · 2026Article
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- M2-associated microglial states in oligodendrocyte regulation and white matter repair in vascular dementia.Journal of translational medicine · 2026Review
- PVT inhibition mitigates neuropathology and cognitive deficits in chronic cerebral hypoperfusion.iScience · 2026Article
- Cholesterol Drives IFITM3CNS neuroscience & therapeutics · 2026Article
- Pentoxifylline targets TLR4/MyD88/NF-κB signaling to ameliorate neuroinflammation and metabolic dysfunction in a rat model of chronic hypoperfusion-induced vascular cognitive impairment.Metabolic brain disease · 2026Article
- Melatonin promotes recovery from ischemic stroke by modulating microglia polarization and inhibiting oligodendrocyte pyroptosis via the RORα/AMPKα/STAT1 pathway.Journal of translational medicine · 2026Article
- Human umbilical cord blood mononuclear cells ameliorate vascular dementia by modulating microglial myelin debris handling and white matter injury.Journal of neuroinflammation · 2026Article
- Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Physical exercise promotes white matter repair after ischemic stroke.Neural regeneration research · 2026Article
- Gut Lachnospiraceae improves white matter injury-related cognitive decline by increasing L-arginine.Cellular & molecular biology letters · 2026Article
- AXL Promotes Ischemic Myelin Repair Through Alleviating Myelin Debris Deposition and Lipid Droplets Accumulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 3D-bioprinted adipose-derived stem cell-secreted GAS6Journal of nanobiotechnology · 2026Article
- Notch-1 suppressed vascular dementia via modulating AMPK/mTOR/TFEB/YAP signaling induced ferroptosis.European journal of medical research · 2026Article
- Exploring Exercise-Linked Neurovascular Unit Adaptations and Sema3G Pathway Involvement in Rats with Vascular Cognitive Impairment.Neurochemical research · 2026Article
- Microglial handling of myelin debris and remyelination after ischaemic stroke: recognition, intracellular processing, lipid fate, and oligodendroglial repair.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
- Mertk promotes early microglial-mediated synaptic engulfment in Alzheimer's disease.Theranostics · 2026Article
- Vitamin B12-Loaded Chitosan Nanoparticles Promote Skeletal Muscle Injury Repair in Aged Rats via Amelioration of Aging-Suppressed Efferocytosis.Biomolecules · 2025Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundVascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD.
methodsBilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor.
resultsHere, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression.
conclusionsCollectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia.
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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 OpenQuestion graph.