ArticleThe Journal of cell biology2000
Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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The trial behind it
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Who cites it
70 citing papers in PubMed, 180 citations in OpenAlex.
- Trial
- Host Response Impairs Tissue Integration of a Fibrin Hydrogel Scaffold Containing Poly(ε-caprolactone) Nanofibers for Peripheral Nerve Repair.Biomimetics (Basel, Switzerland) · 2026Article
- TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.Acta neuropathologica · 2024Article
- PXL01 alters macrophage response with no effect on axonal outgrowth or Schwann cell response after nerve repair in rats.Regenerative medicine · 2024Article
- Gain-of-function mutations of TRPV4 acting in endothelial cells drive blood-CNS barrier breakdown and motor neuron degeneration in mice.Science translational medicine · 2024Article
- Tale of two systems: the intertwining duality of fibrinolysis and lipoprotein metabolism.Journal of thrombosis and haemostasis : JTH · 2023Review
- Cellular mechanisms of fibrin (ogen): insight from neurodegenerative diseases.Frontiers in neuroscience · 2023Review
- PKCδ-positive GABAergic neurons in the central amygdala exhibit tissue-type plasminogen activator: role in the control of anxiety.Molecular psychiatry · 2022Article
- Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves.Biomolecules · 2021Review
- Tissue Plasminogen Activator Loaded PCL Nanofibrous Scaffold Promoted Nerve Regeneration After Sciatic Nerve Transection in Male Rats.Neurotoxicity research · 2021Article
- A Review on the Mechanism of Tuina Promoting the Recovery of Peripheral Nerve Injury.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Blocking PDGF-CC signaling ameliorates multiple sclerosis-like neuroinflammation by inhibiting disruption of the blood-brain barrier.Scientific reports · 2020Article
- Effects of Pacap on Schwann Cells: Focus on Nerve Injury.International journal of molecular sciences · 2020Review
- The multifaceted role of plasminogen in inflammation.Cellular signalling · 2020Review
- Muscarinic receptors modulate Nerve Growth Factor production in rat Schwann-like adipose-derived stem cells and in Schwann cells.Scientific reports · 2020Article
- The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1.Frontiers in cellular neuroscience · 2019Review
- Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics.Nature reviews. Neuroscience · 2018Review
- Low preoperative fibrinogen level is risk factor for neurological complications in acute aortic dissection.Medicine · 2018Observational
- Ischemia-Reperfusion Injury of Sciatic Nerve in Rats: Protective Role of Combination of Vitamin C with E and Tissue Plasminogen Activator.Neurochemical research · 2018Article
- A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis.Frontiers in neurology · 2018Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin and can trigger the degradation of extracellular matrix proteins. In the nervous system, under noninflammatory conditions, tPA contributes to excitotoxic neuronal death, probably through degradation of laminin. To evaluate the contribution of extracellular proteolysis in inflammatory neuronal degeneration, we performed sciatic nerve injury in mice. Proteolytic activity was increased in the nerve after injury, and this activity was primarily because of Schwann cell-produced tPA. To identify whether tPA release after nerve damage played a beneficial or deleterious role, we crushed the sciatic nerve of mice deficient for tPA. Axonal demyelination was exacerbated in the absence of tPA or plasminogen, indicating that tPA has a protective role in nerve injury, and that this protective effect is due to its proteolytic action on plasminogen. Axonal damage was correlated with increased fibrin(ogen) deposition, suggesting that this protein might play a role in neuronal injury. Consistent with this idea, the increased axonal degeneration phenotype in tPA- or plasminogen-deficient mice was ameliorated by genetic or pharmacological depletion of fibrinogen, identifying fibrin as the plasmin substrate in the nervous system under inflammatory axonal damage. This study shows that fibrin deposition exacerbates axonal injury, and that induction of an extracellular proteolytic cascade is a beneficial response of the tissue to remove fibrin. tPA/plasmin-mediated fibrinolysis may be a widespread protective mechanism in neuroinflammatory pathologies.
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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.