ArticlePloS one2016
Endothelial-Specific EphA4 Negatively Regulates Native Pial Collateral Formation and Re-Perfusion following Hindlimb Ischemia.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Leptomeningeal Collaterals Constitute an Immune-Responsive Vascular Niche in Ischemic Stroke.Stroke · 2026Article
- Tie2-Dependent Mechanisms Influence Leptomeningeal Collateral Dynamics and Reperfusion Following Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Meningeal vascular Aβ deposition associates with cerebral hypoperfusion and compensatory collateral remodeling.Alzheimer's research & therapy · 2025Article
- Skull bone marrow-derived immune cells infiltrate the injured cerebral cortex and exhibit anti-inflammatory properties.Brain, behavior, and immunity · 2025Article
- 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
- Monocyte proinflammatory phenotypic control by ephrin type A receptor 4 mediates neural tissue damage.JCI insight · 2022Article
- Formation and Maintenance of the Natural Bypass Vessels of the Brain.Frontiers in cardiovascular medicine · 2022Review
- Noninvasive Low-Intensity Focused Ultrasound Mediates Tissue Protection following Ischemic Stroke.BME frontiers · 2022Article
- Human urine-derived stem cell-derived exosomal miR-21-5p promotes neurogenesis to attenuate Rett syndrome via the EPha4/TEK axis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Conditional Deletion of EphA4 on Cx3cr1-Expressing Microglia Fails to Influence Histopathological Outcome and Blood Brain Barrier Disruption Following Brain Injury.Frontiers in molecular neuroscience · 2021Article
- Abrogation of atypical neurogenesis and vascular-derived EphA4 prevents repeated mild TBI-induced learning and memory impairments.Scientific reports · 2020Article
- EphA4/Tie2 crosstalk regulates leptomeningeal collateral remodeling following ischemic stroke.The Journal of clinical investigation · 2020Article
- Peripheral loss of EphA4 ameliorates TBI-induced neuroinflammation and tissue damage.Journal of neuroinflammation · 2019Article
- Angiopoietin/Tie2 Axis Regulates the Age-at-Injury Cerebrovascular Response to Traumatic Brain Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- A Novel Technique for Visualizing and Analyzing the Cerebral Vasculature in Rodents.Translational stroke research · 2018Article
- Temporal remodeling of pial collaterals and functional deficits in a murine model of ischemic stroke.Journal of neuroscience methods · 2018Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Leptomeningeal anastomoses play a critical role in regulating vascular re-perfusion following obstruction, however, the mechanisms regulating their development remains under investingation. Our current findings indicate that EphA4 receptor is a novel negative regulator of collaterogenesis. We demonstrate that EphA4 is highly expressed on pial arteriole collaterals at post-natal day (P) 1 and 7, then significantly reduced by P21. Endothelial cell (EC)-specific loss of EphA4, EphA4f/f/Tie2::Cre (KO), resulted in an increase in the density but not diameter of pial collaterals compared to WT mice. ECs isolated from KO mice displayed a 3-fold increase in proliferation, enhanced migration, tube formation and elevated levels of phospho(p)-Akt compared to WT ECs. Attenuating p-Akt, using LY294002, reduced the proliferative and migration effects in the KO ECs. RNAseq analysis also revealed altered expression patterns for genes that regulate cell proliferation, vascular development, extracellular matrix and immune-mediate responses, namely MCP-1, MMP2 and angiopoietin-1. Lastly, we show that induction of hindlimb ischemia resulted in accelerated re-perfusion, collateral remodeling and reduced tissue necrosis in the absence of EC-specific EphA4 compared to WT mice. These findings demonstrate a novel role for EphA4 in the early development of the pial collateral network and suggests a role in regulating vascular remodeling after obstruction.
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Registered trials
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