ArticleEuropean journal of pharmacology2015
Bryostatin extends tPA time window to 6 h following middle cerebral artery occlusion in aged female rats.
Article in European journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Bryostatin-1 improves function in arteries with suppressed endothelial cell autophagy.GeroScience · 2026Article
- FDCA Attenuates Neuronal Ferroptosis and Reduces Hemorrhagic Transformation After Ischemic Stroke with High Glucose.Cellular and molecular neurobiology · 2026Article
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- A Brain-Protective Sterol from Soft Coral Inhibits Lipopolysaccharide-Induced Matrix Metalloproteinase-9-Mediated Astrocytic Migration.Biomedicines · 2024Article
- Innovations in Breaking Barriers: Liposomes as Near-Perfect Drug Carriers in Ischemic Stroke Therapy.International journal of nanomedicine · 2024Review
- NPD1 Plus RvD1 Mediated Ischemic Stroke Penumbra Protection Increases Expression of Pro-homeostatic Microglial and Astrocyte Genes.Cellular and molecular neurobiology · 2023Article
- Anti-Inflammatory Effects of Bioactive Compounds from Seaweeds, Bryozoans, Jellyfish, Shellfish and Peanut Worms.Marine drugs · 2023Review
- Impaired angiogenesis in ageing: the central role of the extracellular matrix.Journal of translational medicine · 2023Review
- Bryostatin-1: a promising compound for neurological disorders.Frontiers in pharmacology · 2023Review
- Article
- Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke.Molecular neurobiology · 2021Review
- Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: A translational perspective.Experimental neurology · 2021Review
- Current advances in ischemic stroke research and therapies.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- DHA Attenuates Hypoxia/Reoxygenation Injury by Activating SSeCKS in Human Cerebrovascular Pericytes.Neurochemical research · 2020Article
- Opioid antagonists as potential therapeutics for ischemic stroke.Progress in neurobiology · 2019Review
- tPA Helpers in the Treatment of Acute Ischemic Stroke: Are They Ready for Clinical Use?Journal of stroke · 2019Review
- Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches.European journal of pharmacology · 2018Review
- Inhibition of Inflammation, Suppression of Matrix Metalloproteinases, Induction of Neurogenesis, and Antioxidant Property Make Bryostatin-1 a Therapeutic Choice for Multiple Sclerosis.Frontiers in pharmacology · 2018Article
- Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment.International journal of molecular sciences · 2017Review
- Strategies to Extend Thrombolytic Time Window for Ischemic Stroke Treatment: An Unmet Clinical Need.Journal of stroke · 2017Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) following ischemic/reperfusion injury contributes to post-stroke morbidity and mortality. Bryostatin, a potent protein kinase C (PKC) modulator, has shown promise in treating neurological injury. In the present study, we tested the hypothesis that administration of bryostatin would reduce BBB disruption and HT following acute ischemic stroke; thus, prolonging the time window for administering recombinant tissue plasminogen activator (r-tPA). Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20-month-old female rats using an autologous blood clot with delayed r-tPA reperfusion. Bryostatin (or vehicle) was administered at 2 h post-MCAO and r-tPA was administered at 6 h post-MCAO. Functional assessment, lesion volume, and hemispheric swelling measurements were performed at 24 h post-MCAO. Assessment of BBB permeability, measurement of hemoglobin, assessment of matrix metalloproteinase (MMP) levels by gel zymography, and measurement of PKCε, PKCα, PKCδ expression by western blot were conducted at 24 h post-MCAO. Rats treated with bryostatin prior to r-tPA administration had decreased mortality and hemispheric swelling when compared with rats treated with r-tPA alone. Administration of bryostatin also limited BBB disruption and HT and down-regulated MMP-9 expression while up-regulating PKCε expression at 24 h post-MCAO. Bryostatin administration ameliorates BBB disruption and reduces the risk of HT by down-regulating MMP-9 activation and up-regulating PKCε. In this proof-of-concept study, bryostatin treatment lengthened the time-to-treatment window and enhanced the efficacy and safety of thrombolytic therapy.
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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.