ArticleBrain pathology (Zurich, Switzerland)2025
Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke.
Article in Brain pathology (Zurich, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical and preclinical evidence of meningeal immunity and glymphatic pathways in stroke: a systematic review.Frontiers in immunology · 2026Pooled it
- Chandipura virus encephalitis: an emerging pediatric neurotropic threat in india-virology, epidemiology, pathogenesis, and public health challenges.Journal of neurovirology · 2026Review
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- Integrated Multi-Omics Identifies Core Molecular Targets in Cerebral Venous Sinus Thrombosis-Induced Brain Injury.Biomedicines · 2026Article
- Glymphatic System Dysfunction in Central Nervous System Diseases.CNS neuroscience & therapeutics · 2026Review
- Role of TRP channels in lymphatic function.Frontiers in physiology · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Potential Therapeutic Targets and Emerging Strategies to Promote Hematoma Resolution in Intracerebral Hemorrhage.Revista de neurologia · 2025Review
- Targeting TRPV4 to restore glymphatic system function and alleviate cerebral edema in ischemic stroke.Brain pathology (Zurich, Switzerland) · 2025Article
- The Collapse of Brain Clearance: Glymphatic-Venous Failure, Aquaporin-4 Breakdown, and AI-Empowered Precision Neurotherapeutics in Intracranial Hypertension.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Emerging studies underscore the pivotal role of glymphatic system (GS) dysfunction in the pathogenesis of cerebral edema following brain injury. The transient receptor potential vanilloid 4 (TRPV4) channels have been implicated in modulating the polarization of aquaporin-4 (AQP4), a key protein involved in GS function. This study investigates the potential of targeting TRPV4 to alleviate GS dysfunction and reduce cerebral edema following ischemic stroke. TRPV4 inhibitor HC067047 or a vehicle was administered via lateral ventricle cannulation in a mouse model of middle cerebral artery occlusion and reperfusion (MCAO/R). The function of the GS was assessed through tracer injection experiments, including in vivo transcranial imaging, ex vivo brain tissue and section analysis, and fluorescence retention in deep cervical lymph nodes (dCLNs). Cerebral edema was quantified using magnetic resonance imaging. AQP4 polarization and β-dystroglycan (β-DG) expression were evaluated by immunofluorescence. Western blotting was employed to measure protein levels of β-DG, matrix metalloproteinase-9 (MMP9), and Ras homolog family member A (RhoA). Long-term neurological outcomes were assessed via behavioral testing. MCAO/R mice exhibited significant GS dysfunction, cerebral edema, and disrupted AQP4 polarization. Additionally, β-DG expression was markedly reduced, while TRPV4 expression was elevated in the ischemic penumbra. Western blotting revealed increased expression of MMP9 and RhoA. The inhibition of TRPV4 by HC067047 significantly improved GS function, reduced cerebral edema, and enhanced neurological recovery. Mechanistically, HC067047 partially restored AQP4 polarization, upregulated β-DG expression, and suppressed the expression of MMP9 and RhoA. These findings highlight the therapeutic potential of TRPV4 inhibition in ischemic stroke by restoring GS function, mitigating cerebral edema, and promoting neurological recovery, thereby positioning TRPV4 as a promising target for future interventions.
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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 Socratic graph.