Tissue plasminogen activator prevents white matter damage following stroke
| Autor: | Eric Maubert, Richard Macrez, Jérôme Parcq, Fabian Docagne, Yannick Hommet, Maxime Gauberti, Carine Ali, Axel Montagne, Miriam Hernangómez, Carmen Guaza, Pauline Obiang, Géraldine Liot, Denis Vivien, Fernando Correa |
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| Rok vydání: | 2011 |
| Předmět: |
Aging
Pathology medicine.medical_treatment Apoptosis Endothelium Vascular -- cytology Tissue plasminogen activator Mice Stroke -- pathology Immunology and Allergy Extracellular Signal-Regulated MAP Kinases Brain Injuries -- pathology integumentary system Caspase 3 Brain Sciences bio-médicales et agricoles Extracellular Signal-Regulated MAP Kinases -- metabolism Epidermal Growth Factor -- chemistry Stroke Cytokines -- metabolism Oligodendroglia medicine.anatomical_structure Cytokine Tissue Plasminogen Activator Cytokines medicine.symptom medicine.drug medicine.medical_specialty Immunology Ischemia Biology Article White matter Internal medicine Brain -- pathology medicine Animals Humans Cell Lineage Epidermal Growth Factor Caspase 3 -- metabolism Tissue Plasminogen Activator -- metabolism medicine.disease Oligodendrocyte Mice Inbred C57BL Endocrinology Mechanism of action Brain Injuries Oligodendroglia -- cytology Endothelium Vascular |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname The Journal of experimental medicine, 208 (6 The Journal of Experimental Medicine |
| Popis: | 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. Journal Article Research Support, Non-U.S. Gov't info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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