ArticleThe Journal of clinical investigation2020
EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 57 citations in OpenAlex.
- Leptomeningeal Collaterals Constitute an Immune-Responsive Vascular Niche in Ischemic Stroke.Stroke · 2026Article
- Factors Associated with Leptomeningeal Collaterals and Their Impact on Functional Outcomes in Anterior Circulation Acute Ischemic Stroke.Annals of Indian Academy of Neurology · 2026Article
- Serum EphA4 is Associated with both Parenchymal Hematoma and Increased Blood-Brain Barrier Permeability after Ischemic Stroke.Neurocritical care · 2026Article
- Tie2-Dependent Mechanisms Influence Leptomeningeal Collateral Dynamics and Reperfusion Following Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- After Traumatic Brain Injury, EPHA4 Enhances Endoplasmic Reticulum Stress to Promote M1 Microglial Polarization Through the MAPK Signaling Pathway.Mediators of inflammation · 2026Article
- Hematopoietic EphA4 deficiency alters microglial heterogeneity and improves chronic spatial memory after brain injury.Scientific reports · 2025Article
- Meningeal vascular Aβ deposition associates with cerebral hypoperfusion and compensatory collateral remodeling.Alzheimer's research & therapy · 2025Article
- Integrated Strategies for Targeting Arteriogenesis and Angiogenesis After Stroke.Translational stroke research · 2025Review
- The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination.Nature cardiovascular research · 2025Article
- Long non-coding RNA SNHG12 regulates leptomeningeal collateral remodeling via RGMa after ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.Scientific reports · 2024Article
- Inhibition of EphA4 reduces vasogenic edema after experimental stroke in mice by protecting the blood-brain barrier integrity.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Remote Ischemic Conditioning Enhances Collateral Circulation Through Leptomeningeal Anastomosis and Diminishes Early Ischemic Lesions and Infarct Volume in Middle Cerebral Artery Occlusion.Translational stroke research · 2024Article
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Efferocytosis is restricted by axon guidance molecule EphA4 via ERK/Stat6/MERTK signaling following brain injury.Journal of neuroinflammation · 2023Article
- Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Collateral Circulation in Ischemic Stroke: An Updated Review.Journal of stroke · 2023Review
- Article
- Radiation prevents tumor progression by inhibiting the miR‑93‑5p/EphA4/NF‑κB pathway in triple‑negative breast cancer.Oncology reports · 2023Article
- Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4.Aging cell · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Leptomeningeal anastomoses or pial collateral vessels play a critical role in cerebral blood flow (CBF) restoration following ischemic stroke. The magnitude of this adaptive response is postulated to be controlled by the endothelium, although the underlying molecular mechanisms remain under investigation. Here we demonstrated that endothelial genetic deletion, using EphA4fl/fl/Tie2-Cre and EphA4fl/fl/VeCahderin-CreERT2 mice and vessel painting strategies, implicated EphA4 receptor tyrosine kinase as a major suppressor of pial collateral remodeling, CBF, and functional recovery following permanent middle cerebral artery occlusion. Pial collateral remodeling is limited by the crosstalk between EphA4-Tie2 signaling in vascular endothelial cells, which is mediated through p-Akt regulation. Furthermore, peptide inhibition of EphA4 resulted in acceleration of the pial arteriogenic response. Our findings demonstrate that EphA4 is a negative regulator of Tie2 receptor signaling, which limits pial collateral arteriogenesis following cerebrovascular occlusion. Therapeutic targeting of EphA4 and/or Tie2 represents an attractive new strategy for improving collateral function, neural tissue health, and functional recovery following ischemic stroke.
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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.