ArticleJournal of the neurological sciences2012
Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties.
Article in Journal of the neurological sciences, 2012. 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, 30 citations in OpenAlex.
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Reprogramming of pathogenic strategies inFrontiers in cellular and infection microbiology · 2026Article
- In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Bioengineered 3D microvessels and complementary animal models reveal mechanisms of Trypanosoma congolense sequestration.Communications biology · 2025Article
- The Protein Kinase A Inhibitor KT5720 Prevents Endothelial Dysfunctions Induced by High-Dose Irradiation.International journal of molecular sciences · 2024Article
- Pulmonary arterial hypertension drugs can partially restore altered angiogenic capacities inPulmonary circulation · 2023Article
- Article
- Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench.Aging and disease · 2021Review
- PDE3-inhibitor enoximone prevented mechanical ventilation in patients with SARS-CoV-2 pneumonia.Experimental lung research · 2021Article
- PDE3 Inhibition Reduces Epithelial Mast Cell Numbers in Allergic Airway Inflammation and Attenuates Degranulation of Basophils and Mast Cells.Frontiers in pharmacology · 2020Article
- A Mechanistic Rationale for PDE-4 Inhibitors to Treat Residual Cognitive Deficits in Acquired Brain Injury.Current neuropharmacology · 2020Review
- miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells.Molecular neurobiology · 2019Article
- A pathophysiological role of PDE3 in allergic airway inflammation.JCI insight · 2018Article
- Effects of phosphodiesterase 3A modulation on murine cerebral microhemorrhages.Journal of neuroinflammation · 2017Article
- Rolipram improves renal perfusion and function during sepsis in the mouse.The Journal of pharmacology and experimental therapeutics · 2013Article
- Review
- Cilostazol strengthens barrier integrity in brain endothelial cells.Cellular and molecular neurobiology · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeBrain microvascular disorders, including cerebral microscopic hemorrhage, have high prevalence but few treatment options. To develop new strategies for these disorders, we analyzed the effects of several phosphodiesterase (PDE) inhibitors on human brain microvascular endothelial cells (HBECs).
methodsWe modified barrier properties and response to histamine of HBECs using cilostazol (PDE3 inhibitor), rolipram (PDE4 inhibitor), and dipyridamole (non-specific PDE inhibitor).
resultsCilostazol and dipyridamole altered the distribution of endothelial F-actin. Cilostazol increased expression of tight junction protein claudin-5 by 118% compared to control (p<.001). Permeability to albumin was decreased by cilostazol (21% vs control, p<.05), and permeability to dextran (70Kd) was decreased by both cilostazol (37% vs control, p<.001) and dipyridamole (44% vs control, p<.0001). Cilostazol increased trans-endothelial electrical resistance (TEER) after 12h by 111% compared to control (p<.0001). Protein kinase A (PKA) inhibitors H89 and KT5720 attenuated the TEER increase by cilostazol. Transient increased permeability in response to histamine was significantly mitigated by cilostazol, but not by other PDE inhibitors.
conclusionsThese findings demonstrate distinctive effects of cilostazol and other PDE inhibitors on HBECs, including enhanced barrier characteristics and mitigation of response to histamine. PKA-mediated effects of cilostazol were prominent in this model. These in vitro findings are consistent with therapeutic potential of PDE inhibitors in human brain microvascular disorders.
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Registered trials
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