ArticlePloS one2017
Selective inhibition of brain endothelial Rho-kinase-2 provides optimal protection of an in vitro blood-brain barrier from tissue-type plasminogen activator and plasmin.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Adipose tissue-derived small extracellular vesicles and blood-brain barrier function in adults with overweight and obesity.Experimental physiology · 2026Trial
- Antipsychotic-like effects of the selective Rho-kinase 2 inhibitor KD025 in genetic and pharmacological mouse models of schizophrenia.Molecular psychiatry · 2026Article
- Distinct Effects of Nonselective Rho-Kinase Inhibitor Fasudil and Selective Rho-Kinase 2 Inhibitor KD025 on Serotonin and Dopamine Release in the Nucleus Accumbens of Mice.Neuropsychopharmacology reports · 2026Article
- Preserving Blood-Brain Barrier Integrity in Ischemic Stroke: a Review on MSCs-sEVs Content and Potential Molecular Targets.Molecular neurobiology · 2025Review
- Article
- Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics.Signal transduction and targeted therapy · 2025Review
- The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- [Restraint stress induces blood-brain barrier injury in rat amygdala by activating the Rho/ROCK signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Article
- Three-dimensional bioprinting of stem cell-derived central nervous system cells enables astrocyte growth, vasculogenesis, and enhances neural differentiation/function.Biotechnology and bioengineering · 2023Article
- Article
- Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus.Journal of clinical medicine · 2022Review
- Activation of non-classical NMDA receptors by glycine impairs barrier function of brain endothelial cells.Cellular and molecular life sciences : CMLS · 2022Article
- The Role of Fibrinolytic System in Health and Disease.International journal of molecular sciences · 2022Article
- Transcriptome analysis of fasudil treatment in the APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease.Scientific reports · 2022Article
- Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy.International journal of molecular sciences · 2021Article
- Collagen-Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis.Journal of the American Heart Association · 2021Article
- Cognitive Dysfunction in Systemic Lupus Erythematosus: Immunopathology, Clinical Manifestations, Neuroimaging and Management.Rheumatology and therapy · 2021Review
- Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites.Frontiers in aging neuroscience · 2021Article
- Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia.Neural regeneration research · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model. ROCK-2 was highly expressed relative to ROCK-1 in all human and mouse brain cell types and particularly enriched in rodent brain endothelial cells and astrocytes compared to neurons. KD025 was more potent than fasudil in attenuation of rt-PA- and plasminogen-induced BBB permeation under normoxia, but especially under stroke-like conditions. Importantly, only KD025, but not fasudil, was able to block rt-PA-dependent permeability increases, morphology changes and tight junction degradation in isolated BECs. Selective ROCK-2 inhibition further diminished rt-PA-triggered myosin phosphorylation, shape alterations and matrix metalloprotease activation in astrocytes. These findings highlight ROCK-2 as the key isoform driving BBB impairment and brain endothelial damage by rt-PA and the potential of KD025 to optimally protect the BBB during thrombolysis.
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Registered trials
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