Protective Role of Reactive Astrocytes in Brain Ischemia
| Autor: | Karina Aprico, Andrew P. Fotheringham, Nobuo Nagai, Ioan Davies, Lieve Moons, Fredrik Blomstrand, Ulrika Wilhelmsson, Kerstin Larsson, Daniel Andersson, Andrea C. Pardo, Michael Nilsson, Nicholas J. Maragakis, Andrea Lundkvist, Anders Ståhlberg, Takeshi Yabe, Joan P. Schwartz, Milos Pekny, Peter Carmeliet, Mikael Kubista, Marcela Pekna, Lizhen Li, Christina Nodin |
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| Rok vydání: | 2007 |
| Předmět: |
Middle Cerebral Artery
Pathology medicine.medical_specialty Glutamic Acid Vimentin Brain Ischemia Brain ischemia Mice chemistry.chemical_compound Glial Fibrillary Acidic Protein Plasminogen Activator Inhibitor 1 medicine Animals Mice Knockout Glial fibrillary acidic protein biology Gap junction Glutamate receptor Gap Junctions medicine.disease Receptor Endothelin B Molecular biology medicine.anatomical_structure Neurology chemistry Astrocytes Plasminogen activator inhibitor-1 biology.protein Neurology (clinical) Cardiology and Cardiovascular Medicine Plasminogen activator Astrocyte |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 28:468-481 |
| ISSN: | 1559-7016 0271-678X |
| Popis: | Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament (IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP−/−Vim−/− mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery (MCA) transection, infarct volume was 210 to 350% higher in GFAP−/−Vim−/− than in wild-type (WT) mice; GFAP−/−, Vim−/− and WT mice had the same infarct volume. Endothelin B receptor (ETBR) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP−/−Vim−/− astrocytes. In WT astrocytes, ETBR colocalized extensively with bundles of IFs. GFAP−/−Vim−/− astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP−/−Vim−/− than in WT mice. DNA array analysis and quantitative real-time PCR showed downregulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ETBR-mediated control of gap junctions, and PAI-1 expression. |
| Databáze: | OpenAIRE |
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