EMMPRIN/CD147 plays a detrimental role in clinical and experimental ischemic stroke
| Autor: | Fudong Liu, Rodney M. Ritzel, Yun-Ju Lai, Jun Li, Julia Kofler, Rajkumar Verma, Meaghan Roy-O'Reilly, Sami Tarabishy, Sarah J. Doran, Louise D. McCullough, Anjali Chauhan, Ilene Staff, Hilda Ahnstedt, Anthony Patrizz, Anita R. Patel, Gillian Weston |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Aging medicine.medical_specialty middle cerebral artery occlusion EMMPRIN Disease Matrix metalloproteinase Blood–brain barrier Mice Internal medicine medicine Animals Humans cardiovascular diseases Aged Ischemic Stroke Secondary hemorrhage Aged 80 and over Microglia business.industry Endothelial Cells Cell Biology Middle Aged medicine.disease stroke Peripheral Disease Models Animal medicine.anatomical_structure Matrix Metalloproteinase 9 Blood-Brain Barrier Astrocytes Ischemic stroke Basigin CD147 Cardiology Female business Infiltration (medical) Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.102935 |
| Popis: | Background: Ischemic stroke is a devastating disease, often resulting in death or permanent neurological deficits. EMMPRIN/CD147 is a plasma membrane protein that induces the production of matrix metalloproteinases (MMPs), which contribute to secondary damage after stroke by disrupting the blood brain barrier (BBB) and facilitating peripheral leukocyte infiltration into the brain. Results: CD147 surface expression increased significantly after stroke on infiltrating leukocytes, astrocytes and endothelial cells, but not on resident microglia. Inhibition of CD147 reduced MMP levels, decreased ischemic damage, and improved functional, cognitive and histological outcomes after experimental ischemic stroke in both young and aged mice. In stroke patients, high levels of serum CD147 24 hours after stroke predicted poor functional outcome at 12 months. Brain CD147 levels were correlated with MMP-9 and secondary hemorrhage in post-mortem samples from stroke patients. Conclusions: Acute inhibition of CD147 decreases levels of MMP-9, limits tissue loss, and improves long-term cognitive outcomes following experimental stroke in aged mice. High serum CD147 correlates with poor outcomes in stroke patients. This study identifies CD147 as a novel, clinically relevant target in ischemic stroke. |
| Databáze: | OpenAIRE |
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