ArticleCellular and molecular neurobiology2013
Cilostazol strengthens barrier integrity in brain endothelial cells.
Article in Cellular and molecular neurobiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05836766 (Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion), which is not on this map. Cited by 22 papers.
What it found
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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.
Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: A Phase Ⅱa,Prospective,Multicenter,Randomized, Double-blind,Placebo-controlled Parallel Trial
Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Temporal Mapping of CSVD-Related White Matter Lesions and Concurrent Neurovascular Dysfunction in Spontaneously Hypertensive Rats.CNS neuroscience & therapeutics · 2026Article
- Efficacy and safety of sublingual cilostazol and dexborneol for the treatment of acute ischaemic stroke: a randomised phase 2 trial in China.EClinicalMedicine · 2026Article
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Impact of direct oral anticoagulants on blood-brain barrier integrity.IBRO neuroscience reports · 2025Article
- Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure.Toxicological research · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Defective Function of the Blood-Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model.Cellular and molecular neurobiology · 2022Article
- Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems.Pharmaceutics · 2021Review
- Review
- Transdermal System Based on Solid Cilostazol Nanoparticles Attenuates Ischemia/Reperfusion-Induced Brain Injury in Mice.Nanomaterials (Basel, Switzerland) · 2021Article
- Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction.Frontiers in cellular neuroscience · 2021Review
- Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer's Disease.International journal of molecular sciences · 2020Review
- miRNA-27a-3p and miRNA-222-3p as Novel Modulators of Phosphodiesterase 3a (PDE3A) in Cerebral Microvascular Endothelial Cells.Molecular neurobiology · 2019Article
- Association Between Sumatriptan Treatment During a Migraine Attack and Central 5-HT1B Receptor Binding.JAMA neurology · 2019Article
- Recent Expansions on Cellular Models to Uncover the Scientific Barriers Towards Drug Development for Alzheimer's Disease.Cellular and molecular neurobiology · 2019Review
- Development of a Multicomponent Intervention to Prevent Alzheimer's Disease.Frontiers in neurology · 2019Review
- Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton.American journal of physiology. Cell physiology · 2016Article
- In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2016Review
- Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro.Cellular and molecular neurobiology · 2015Article
- Phosphodiesterase inhibitors as therapeutics for traumatic brain injury.Current pharmaceutical design · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We studied the effect of cilostazol, a selective inhibitor of phosphodiesterase 3, on barrier functions of blood-brain barrier (BBB)-related endothelial cells, primary rat brain capillary endothelial cells (RBEC), and the immortalized human brain endothelial cell line hCMEC/D3. The pharmacological potency of cilostazol was also evaluated on ischemia-related BBB dysfunction using a triple co-culture BBB model (BBB Kit™) subjected to 6-h oxygen glucose deprivation (OGD) and 3-h reoxygenation. There was expression of phosphodiesterase 3B mRNA in RBEC, and a significant increase in intracellular cyclic AMP (cAMP) content was detected in RBEC treated with both 1 and 10 μM cilostazol. Cilostazol increased the transendothelial electrical resistance (TEER), an index of barrier tightness of interendothelial tight junctions (TJs), and decreased the endothelial permeability of sodium fluorescein through the RBEC monolayer. The effects on these barrier functions were significantly reduced in the presence of protein kinase A (PKA) inhibitor H-89. Microscopic observation revealed smooth and even localization of occludin immunostaining at TJs and F-actin fibers at the cell borders in cilostazol-treated RBEC. In hCMEC/D3 cells treated with 1 and 10 μM cilostazol for 24 and 96 h, P-glycoprotein transporter activity was increased, as assessed by rhodamine 123 accumulation. Cilostazol improved the TEER in our triple co-culture BBB model with 6-h OGD and 3-h reoxygenation. As cilostazol stabilized barrier integrity in BBB-related endothelial cells, probably via cAMP/PKA signaling, the possibility that cilostazol acts as a BBB-protective drug against cerebral ischemic insults to neurons has to be considered.
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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.