ArticleThe Journal of clinical investigation2010
Tissue-type plasminogen activator is a neuroprotectant in the mouse hippocampus.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 97 citations in OpenAlex.
- Tissue Plasminogen Activator as an Approved Strategy for Ischemic Stroke: A Review of tPA's Structure, Mechanism of Action and the Novel Targeting Methods.Journal of molecular neuroscience : MN · 2025Review
- New Wine in an Old Bottle: tPA for Ischemic Stroke Management.Translational stroke research · 2025Article
- The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons.Cell death & disease · 2024Article
- Perinuclear compartment controls calcineurin/MEF2 signaling for axonal outgrowth of hippocampal neurons.Frontiers in molecular neuroscience · 2024Article
- Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms.Neuroscience bulletin · 2023Review
- Thrombolysis by PLAT/tPA increases serum free IGF1 leading to a decrease of deleterious autophagy following brain ischemia.Autophagy · 2022Article
- Tissue-type plasminogen activator induces TNF-α-mediated preconditioning of the blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.Journal of thrombosis and thrombolysis · 2021Article
- The plasminogen activating system in the pathogenesis of Alzheimer's disease.Neural regeneration research · 2021Review
- 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
- Enzymatically Inactive Tissue-Type Plasminogen Activator Reverses Disease Progression in the Dextran Sulfate Sodium Mouse Model of Inflammatory Bowel Disease.The American journal of pathology · 2021Article
- Research Progress on the Mechanism of Mitochondrial Autophagy in Cerebral Stroke.Frontiers in aging neuroscience · 2021Review
- Urokinase-Type Plasminogen Activator Protects Cerebral Cortical Neurons from Soluble Aβ-Induced Synaptic Damage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Ginkgo biloba extract protects diabetic rats against cerebral ischemia‑reperfusion injury by suppressing oxidative stress and upregulating the expression of glutamate transporter 1.Molecular medicine reports · 2020Article
- 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-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
- 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
- Protease-independent action of tissue plasminogen activator in brain plasticity and neurological recovery after ischemic stroke.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The best-known function of the serine protease tissue-type plasminogen activator (tPA) is as a thrombolytic enzyme. However, it is also found in structures of the brain that are highly vulnerable to hypoxia-induced cell death, where its association with neuronal survival is poorly understood. Here, we have demonstrated that hippocampal areas of the mouse brain lacking tPA activity are more vulnerable to neuronal death following an ischemic insult. We found that sublethal hypoxia, which elicits tolerance to subsequent lethal hypoxic/ischemic injury in a natural process known as ischemic preconditioning (IPC), induced a rapid release of neuronal tPA. Treatment of hippocampal neurons with tPA induced tolerance against a lethal hypoxic insult applied either immediately following insult (early IPC) or 24 hours later (delayed IPC). tPA-induced early IPC was independent of the proteolytic activity of tPA and required the engagement of a member of the LDL receptor family. In contrast, tPA-induced delayed IPC required the proteolytic activity of tPA and was mediated by plasmin, the NMDA receptor, and PKB phosphorylation. We also found that IPC in vivo increased tPA activity in the cornu ammonis area 1 (CA1) layer and Akt phosphorylation in the hippocampus, as well as ischemic tolerance in wild-type but not tPA- or plasminogen-deficient mice. These data show that tPA can act as an endogenous neuroprotectant in the murine hippocampus.
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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.