ArticleFluids and barriers of the CNS2022
Effects of fasudil on blood-brain barrier integrity.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Brain and Liver Dual-Targeting Oridonin Nanoparticles to Enhance Aβ Clearance for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- Integrative multi-omics analysis reveals inflammation-related molecular networks in acute mountain sickness.Frontiers in immunology · 2026Article
- Impact of direct oral anticoagulants on blood-brain barrier integrity.IBRO neuroscience reports · 2025Article
- Effects of fasudil against photothrombotic stroke in genetically modified obese (ob/ob) mice.Metabolic brain disease · 2025Article
- Article
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Microcirculation Dysfunction in Subacute Stroke: The Role of Delayed Capillary Pericyte Loss.Aging and disease · 2025Article
- Article
- Investigation of blood-brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide.Toxicology and environmental health sciences · 2025Article
- Fasudil attenuates lipopolysaccharide-induced cognitive impairment in C57BL/6 mice through anti-oxidative and anti-inflammatory effects: Possible role of aquaporin-4.IBRO neuroscience reports · 2024Article
- Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway.Free radical biology & medicine · 2024Article
- Augmentation of functional recovery viaJournal of orthopaedic translation · 2024Article
- Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Application of parallel artificial membrane permeability assay technique and chemometric modeling for blood-brain barrier permeability prediction of protein kinase inhibitors.Future medicinal chemistry · 2024Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundCerebral infarction accounts for 85% of all stroke cases. Even in an era of rapid and effective recanalization using an intravascular approach, the majority of patients have poor functional outcomes. Thus, there is an urgent need for the development of therapeutic agents to treat acute ischemic stroke. We evaluated the effect of fasudil, a Rho kinase inhibitor, on blood brain barrier (BBB) functions under normoxia or oxygen-glucose deprivation (OGD) conditions using a primary cell-based in vitro BBB model.
methodsBBB models from rat primary cultures (brain capillary endothelial cells, astrocytes, and pericytes) were subjected to either normoxia or 6 h OGD/24 h reoxygenation. To assess the effects of fasudil on BBB functions, we evaluated real time impedance, transendothelial electrical resistance (TEER), sodium fluorescein permeability, and tight junction protein expression using western blotting. Lastly, to understand the observed protective mechanism on BBB functions by fasudil we examined the role of cyclooxygenase-2 and thromboxane A2 receptor agonist U-46619 in BBB-forming cells.
resultsWe found that treatment with 0.3-30 µM of fasudil increased cellular impedance. Fasudil enhanced barrier properties in a concentration-dependent manner, as measured by an increased (TEER) and decreased permeability. Fasudil also increased the expression of tight junction protein claudin-5. Reductions in TEER and increased permeability were observed after OGD/reoxygenation exposure in mono- and co-culture models. The improvement in BBB integrity by fasudil was confirmed in both of the models, but was significantly higher in the co-culture than in the monoculture model. Treatment with U-46619 did not show significant changes in TEER in the monoculture model, whereas it showed a significant reduction in TEER in the co-culture model. Fasudil significantly improved the U-46619-induced TEER reduction in the co-culture models. Pericytes and astrocytes have opposite effects on endothelial cells and may contribute to endothelial injury in hyperacute ischemic stroke. Overall, fasudil protects the integrity of BBB both by a direct protective effect on endothelial cells and by a pathway mediated via pericytes and astrocytes.
conclusionsOur findings suggest that fasudil is a BBB-protective agent against acute ischemic stroke.
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