ArticleJournal of neuroinflammation2021
Inhibition of P2X4R attenuates white matter injury in mice after intracerebral hemorrhage by regulating microglial phenotypes.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 32 citations in OpenAlex.
- Selective Kv1.3 inhibition promotes M2 microglial polarization, accelerates hematoma resolution, and improves neurological recovery following collagenase-induced spontaneous intracerebral hemorrhage in mice.Veterinary world · 2026Article
- Reblastatin as a neuroprotective agent in temporal lobe epilepsy and excitotoxic conditions of Alzheimer's disease and Parkinson's disease.Acta pharmaceutica Sinica. B · 2026Article
- Cellular senescence in migraine - a hypothesis-driven narrative review.The journal of headache and pain · 2026Review
- Human umbilical cord mesenchymal stem cells alleviate hypoxic-ischemia-induced white-matter injury in neonatal rats by regulating polarization of microglia.Scientific reports · 2026Article
- Low-Intensity Pulsed Ultrasound Alleviation of LPS-Induced Depression-Like Behavior via Microglial P2X4R Inhibition and BDNF/TrkB Pathway Activation.CNS neuroscience & therapeutics · 2026Article
- TSPO activation ameliorates maternal immune activation induced PV interneuron deficits via BDNF/TrkB signaling.Psychopharmacology · 2025Article
- Extracellular Vesicles From Bone Marrow-Derived Macrophages Enriched in ARG1 Enhance Microglial Phagocytosis and Haematoma Clearance Following Intracerebral Haemorrhage.Journal of extracellular vesicles · 2025Article
- Unveiling the inflammatory messengers after intracerebral hemorrhage: the crosstalk between peripheral NETs and microglia.Frontiers in immunology · 2025Review
- Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice.Cellular and molecular neurobiology · 2023Article
- Article
- Secondary White Matter Injury Mediated by Neuroinflammation after Intracerebral Hemorrhage and Promising Therapeutic Strategies of Targeting the NLRP3 Inflammasome.Current neuropharmacology · 2023Review
- Research progress of endogenous hematoma absorption after intracerebral hemorrhage.Frontiers in neurology · 2023Review
- Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders.Mediators of inflammation · 2022Article
- Metformin Alleviates Neuroinflammation Following Intracerebral Hemorrhage in Mice by Regulating Microglia/Macrophage Phenotype in a Gut Microbiota-Dependent Manner.Frontiers in cellular neuroscience · 2021Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWhite matter injury (WMI) is a major neuropathological event associated with intracerebral hemorrhage (ICH). P2X purinoreceptor 4 (P2X4R) is a member of the P2X purine receptor family, which plays a crucial role in regulating WMI and neuroinflammation in central nervous system (CNS) diseases. Our study investigated the role of P2X4R in the WMI and the inflammatory response in mice, as well as the possible mechanism of action after ICH.
methodsICH was induced in mice via collagenase injection. Mice were treated with 5-BDBD and ANA-12 to inhibit P2X4R and tropomyosin-related kinase receptor B (TrkB), respectively. Immunostaining and quantitative polymerase chain reaction (qPCR) were performed to detect microglial phenotypes after the inhibition of P2X4R. Western blots (WB) and immunostaining were used to examine WMI and the underlying molecular mechanisms. Cylinder, corner turn, wire hanging, and forelimb placement tests were conducted to evaluate neurobehavioral function.
resultsAfter ICH, the protein levels of P2X4R were upregulated, especially on day 7 after ICH, and were mainly located in the microglia. The inhibition of P2X4R via 5-BDBD promoted neurofunctional recovery after ICH as well as the transformation of the pro-inflammatory microglia induced by ICH into an anti-inflammatory phenotype, and attenuated ICH-induced WMI. Furthermore, we found that TrkB blockage can reverse the protective effects of WMI as well as neuroprotection after 5-BDBD treatment. This result indicates that P2X4R plays a crucial role in regulating WMI and neuroinflammation and that P2X4R inhibition may benefit patients with ICH.
conclusionsOur results demonstrated that P2X4R contributes to WMI by polarizing microglia into a pro-inflammatory phenotype after ICH. Furthermore, the inhibition of P2X4R promoted pro-inflammatory microglia polarization into an anti-inflammatory phenotype, enhanced brain-derived neurotrophic factor (BDNF) production, and through the BDNF/TrkB pathway, attenuated WMI and improved neurological function. Therefore, the regulation of P2X4R activation may be beneficial for the reducing of ICH-induced brain injury.
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