ArticleAnnals of clinical and translational neurology2014
Selective ROCK2 Inhibition In Focal Cerebral Ischemia.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 122 citations in OpenAlex.
- Cutting Edge: Selective Oral ROCK2 Inhibitor Reduces Clinical Scores in Patients with Psoriasis Vulgaris and Normalizes Skin Pathology via Concurrent Regulation of IL-17 and IL-10.Journal of immunology (Baltimore, Md. : 1950) · 2017Trial
- Antipsychotic-like effects of the selective Rho-kinase 2 inhibitor KD025 in genetic and pharmacological mouse models of schizophrenia.Molecular psychiatry · 2026Article
- Identifying ROCK2 as an intervention target for bilirubin encephalopathy.Fundamental research · 2026Article
- Adeno-associated virus-mediated inhibition of ROCK2 promotes synaptogenesis and neurogenesis in rats after ischemic stroke.Neural regeneration research · 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
- Selective ROCK2 inhibition reduces microvascular obstruction but does not reduce myocardial infarction after ischaemia and reperfusion.Journal of molecular and cellular cardiology plus · 2026Article
- Targeting MAD2B as a strategy for ischemic stroke therapy.Journal of advanced research · 2025Article
- Rock inhibitors in Alzheimer's disease.Frontiers in aging · 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
- Conditional deficiency of Rho-associated kinases disrupts endothelial cell junctions and impairs respiratory function in adult mice.FEBS open bio · 2024Article
- PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior.Zoological research · 2024Article
- Rhoa/ROCK, mTOR and Secretome-Based Treatments for Ischemic Stroke: New Perspectives.Current issues in molecular biology · 2024Review
- New and Emerging Oral/Topical Small-Molecule Treatments for Psoriasis.Pharmaceutics · 2024Review
- Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes.Frontiers in immunology · 2024Article
- Article
- Promising Cerebral Blood Flow Enhancers in Acute Ischemic Stroke.Translational stroke research · 2023Review
- Genomic and Reverse Translational Analysis Discloses a Role for Small GTPase RhoA Signaling in the Pathogenesis of Schizophrenia: Rho-Kinase as a Novel Drug Target.International journal of molecular sciences · 2023Review
- Article
- Apremilast exerts protective effects on stroke outcomes and blood-brain barrier (BBB) dysfunction through regulating Rho-associated protein kinase 2 expression.Brain and behavior · 2022Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveRho-associated kinase (ROCK) is a key regulator of numerous processes in multiple cell types relevant in stroke pathophysiology. ROCK inhibitors have improved outcome in experimental models of acute ischemic or hemorrhagic stroke. However, the relevant ROCK isoform (ROCK1 or ROCK2) in acute stroke is not known.
methodsWe characterized the pharmacodynamic and pharmacokinetic profile, and tested the efficacy and safety of a novel selective ROCK2 inhibitor KD025 (formerly SLx-2119) in focal cerebral ischemia models in mice.
resultsKD025 dose-dependently reduced infarct volume after transient middle cerebral artery occlusion. The therapeutic window was at least 3 hours from stroke onset, and the efficacy was sustained for at least 4 weeks. KD025 was at least as efficacious in aged, diabetic or female mice, as in normal adult males. Concurrent treatment with atorvastatin was safe, but not additive or synergistic. KD025 was also safe in a permanent ischemia model, albeit with diminished efficacy. As one mechanism of protection, KD025 improved cortical perfusion in a distal middle cerebral artery occlusion model, implicating enhanced collateral flow. Unlike isoform-nonselective ROCK inhibitors, KD025 did not cause significant hypotension, a dose-limiting side effect in acute ischemic stroke.
interpretationAltogether, these data show that KD025 is efficacious and safe in acute focal cerebral ischemia in mice, implicating ROCK2 as the relevant isoform in acute ischemic stroke. Data suggest that selective ROCK2 inhibition has a favorable safety profile to facilitate clinical translation.
Identifiers
What OpenQuestion holds
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.