ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Urokinase-type plasminogen activator promotes dendritic spine recovery and improves neurological outcome following ischemic stroke.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- uPAR exhibits age- and region-dependent expression in the brains of mice with Alzheimer's disease-like pathology.Brain research · 2026Article
- Long-range axon branching: contributions to brain network plasticity and repair.Nature reviews. Neuroscience · 2026Review
- The Plasminogen Activation System in the Central Nervous System: Implications for Epilepsy and Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Identifying new blood biomarkers of neuroplasticity associated with rehabilitation outcomes after stroke.Scientific reports · 2025Observational
- uPAR and cFn as candidate protein biomarkers for identifying low response to rtPA in acute ischemic stroke.European journal of medical research · 2025Article
- Emerging Adulthood Is Marked by a Cortical Dendritic Arborization Phase Depending on the Actin Nucleator Cobl.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Compartmentalized Actions of the Plasminogen Activator Inhibitors, PAI-1 and Nsp, in Ischemic Stroke.Translational stroke research · 2022Article
- Structural plasticity of motor cortices assessed by voxel-based morphometry and immunohistochemical analysis following internal capsular infarcts in macaque monkeys.Cerebral cortex communications · 2022Article
- Poststroke dendritic arbor regrowth requires the actin nucleator Cobl.PLoS biology · 2021Article
- Urokinase-type plasminogen activator promotes N-cadherin-mediated synaptic recovery in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system: implications for neurorepair in the ischemic brain.Neural regeneration research · 2020Review
- Urokinase Plasminogen Activator: A Potential Thrombolytic Agent for Ischaemic Stroke.Cellular and molecular neurobiology · 2020Review
- Urokinase-type plasminogen activator (uPA) regulates the expression and function of growth-associated protein 43 (GAP-43) in the synapse.The Journal of biological chemistry · 2020Article
- Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Urokinase-type plasminogen activator (uPA) protects the tripartite synapse in the ischemic brain via ezrin-mediated formation of peripheral astrocytic processes.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Article
- The Plasminogen Activation System Promotes Neurorepair in the Ischemic Brain.Current drug targets · 2019Review
- Tissue-type plasminogen activator protects the postsynaptic density in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Urokinase-type plasminogen activator (uPA) promotes ezrin-mediated reorganization of the synaptic cytoskeleton in the ischemic brain.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA(-/-)) or uPAR (uPAR(-/-)) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA(-/-) but not in uPAR(-/-) mice. Diffusion tensor imaging studies indicate that uPA(-/-) mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS.
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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.