ArticleThe Journal of experimental medicine2011
Tissue plasminogen activator prevents white matter damage following stroke.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Role and Mechanism of Microglia in White Matter Injury Recovery in Ischemic Stroke.Immunity, inflammation and disease · 2025Pooled it
- Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.Trends in cell biology · 2026Review
- Effects of Repeated Early-life Anesthesia Exposure on Visual System Development in Mice.Anesthesiology · 2026Article
- Neuronal conversion of single-chain tissue-type plasminogen activator into its two-chain form: implications in neurodevelopment, learning, and memory.Cell death & disease · 2025Article
- Tissue-type plasminogen activator expression by endothelial cells and oligodendrocytes is required for proper CNS myelination.Acta neuropathologica communications · 2025Article
- New Wine in an Old Bottle: tPA for Ischemic Stroke Management.Translational stroke research · 2025Article
- Roles of neuroimaging markers and biomarkers in cerebral small vessel disease and their associations with cognitive function.Frontiers in neurology · 2025Review
- The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons.Cell death & disease · 2024Article
- Age-Associated Resilience Against Ischemic Injury in Mice Exposed to Transient Middle Cerebral Artery Occlusion.Molecular neurobiology · 2023Article
- The Role of Matrix Metalloproteinases in Hemorrhagic Transformation in the Treatment of Stroke with Tissue Plasminogen Activator.Journal of personalized medicine · 2023Review
- Modulations of the neuronal trafficking of tissue-type plasminogen activator (tPA) influences glutamate release.Cell death & disease · 2023Article
- White Matter Injury: An Emerging Potential Target for Treatment after Subarachnoid Hemorrhage.Oxidative medicine and cellular longevity · 2023Review
- The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke.Current neuropharmacology · 2023Review
- Low-density lipoprotein receptor-related protein-1 (LRP1) in the glial lineage modulates neuronal excitability.Frontiers in network physiology · 2023Review
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Roles of the tissue-type plasminogen activator in immune response.Cellular immunology · 2022Review
- Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses.Journal of neuroinflammation · 2021Article
- Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury.Current neuropharmacology · 2021Review
- Development and Testing of Thrombolytics in Stroke.Journal of stroke · 2021Review
- Extrinsic Factors Driving Oligodendrocyte Lineage Cell Progression in CNS Development and Injury.Neurochemical research · 2020Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue plasminogen activator (tPA) is the only available treatment for acute stroke. In addition to its vascular fibrinolytic action, tPA exerts various effects within the brain, ranging from synaptic plasticity to control of cell fate. To date, the influence of tPA in the ischemic brain has only been investigated on neuronal, microglial, and endothelial fate. We addressed the mechanism of action of tPA on oligodendrocyte (OL) survival and on the extent of white matter lesions in stroke. We also investigated the impact of aging on these processes. We observed that, in parallel to reduced levels of tPA in OLs, white matter gets more susceptible to ischemia in old mice. Interestingly, tPA protects murine and human OLs from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain. When injected into aged animals, tPA, although toxic to the gray matter, rescues white matter from ischemia independently of its proteolytic activity. These studies reveal a novel mechanism of action of tPA and unveil OL as a target cell for cytokine effects of tPA in brain diseases. They show overall that tPA protects white matter from stroke-induced lesions, an effect which may contribute to the global benefit of tPA-based stroke treatment.
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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.