ArticleFree radical biology & medicine2024
Inhibition of acid-sensing receptor GPR4 attenuates neuronal ferroptosis via RhoA/YAP signaling in a rat model of subarachnoid hemorrhage.
Article in Free radical biology & medicine, 2024. 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.
- Inhibition of GPR4 Ameliorates Neuropathic Pain and Neuronal Ferroptosis via Regulation of Spinal RhoA/YAP Signaling in Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Iron overload induces ROS-mediated neural stem/progenitor cells apoptosis via mTOR pathway.BMC neuroscience · 2026Article
- CTRP3 alleviates neuropathic pain by improving mitochondrial biogenesis and mitochondrial unfolded protein response via spinal SIRT1 in rats.International journal of molecular medicine · 2026Article
- PDZD8 overexpression alleviates early brain injury via regulating MERCs integrity after experimental subarachnoid hemorrhage.Journal of neuroinflammation · 2026Article
- The Mechanism of Ferroptosis and Blood-Brain Barrier Damage in Cerebrovascular Diseases.Biomedicines · 2026Review
- Systematic evaluation of cerebral injury stimulating by underwater infrasound.Frontiers in physiology · 2026Article
- Antagonism of GPR4 with NE 52-QQ57 alleviates gestational diabetes mellitus-induced placental insults mediated by inhibiting NF-κB.Histology and histopathology · 2026Article
- Antagonism of GPR4 with NE 52-QQ57 alleviates gestational diabetes mellitus-induced placental insults mediated by inhibiting NF-κB.Histology and histopathology · 2026Article
- Paricalcitol-mediated vitamin D receptor activation attenuates neuronal ferroptosis via cAMP-PKA-DRP1 signaling pathway after intracerebral hemorrhage.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- GPR4 regulates temporally dynamic and sex-dependent cocaine-induced locomotor sensitization.Frontiers in molecular neuroscience · 2026Article
- The TREM1-AQP4 axis mediates neuroinflammatory injury and brain edema after experimental subarachnoid hemorrhage.European journal of medical research · 2025Article
- Iron Hemostasis in Patients With Subarachnoid Hemorrhage and the Role of Early CSF Drainage.Neurology · 2025Review
- Research progress of early brain Injury in subarachnoid hemorrhage from 2004 to 2024: a bibliometric analysis.Neurosurgical review · 2025Review
- Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.International journal of biological sciences · 2025Review
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19 authors.
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Abstract
background and purposeSubarachnoid hemorrhage (SAH) is a devastating stroke, in which acidosis is one of detrimental complications. The extracellular pH reduction can activate G protein-coupled receptor 4 (GPR4) in the brain. Yet, the extent to which proton-activated GPR4 contributes to the early brain injury (EBI) post-SAH remains largely unexplored. Ferroptosis, iron-dependent programmed cell death, has recently been shown to contribute to EBI. We aimed to investigate the effects of GPR4 inhibition on neurological deficits and neuronal ferroptosis after SAH in rats.
methodsA total 253 Sprague Dawley (SD) male rats (weighing 275-330g) were utilized in this study. SAH was induced by endovascular perforation. NE-52-QQ57 (NE), a selective antagonist of GPR4 was administered intraperitoneally 1-h post-SAH. To explore the mechanisms, RhoA activator U-46619 and YAP activator PY-60 were delivered intracerebroventricularly. Short- and long-term neurobehavior, SAH grading, Western blot assay, ELISA assay, immunofluorescence staining, and transmission electron microscopy was performed post-SAH.
resultsFollowing SAH, there was an upregulation of GPR4 expression in neurons. GPR4 inhibition by NE improved both short-term and long-term neurological outcomes post-SAH. NE also reduced neuronal ferroptosis, as evidenced by decreased lipid peroxidation products 4HNE and MDA levels in brain tissues, and reduced mitochondrial shrinkage, increased mitochondria crista and decreased membrane density. The application of either U-46619 or PY-60 partially offset the neuroprotective effects of NE on neuronal ferroptosis in SAH rats.
conclusionsThis study demonstrated that acid-sensing receptor GPR4 contributed to neuronal ferroptosis after SAH via RhoA/YAP pathway, and NE may be a potential therapeutic strategy to attenuate GPR4 mediated neuronal ferroptosis and EBI after SAH.
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