Protective role of reactive astrocytes in brain ischemia.

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Protective role of reactive astrocytes in brain ischemia.

Li, Lizhen, 1977 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Lundkvist, Andrea, 1975 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Andersson, Daniel, 1979 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Wilhelmsson, Ulrika, 1970 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Nagai, Nobuo (author): Katholieke Universiteit Leuven

Pardo, Andrea C (author): Johns Hopkins University

Nodin, Christina, 1974 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Ståhlberg, Anders, 1975 (author): Chalmers tekniska högskola,Chalmers University of Technology

Aprico, Karina (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Larsson, Kerstin (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,University of Gothenburg

Yabe, Takeshi (author): National Institute of Neurological Disorders and Stroke

Moons, Lieve (author): Katholieke Universiteit Leuven

Fotheringham, Andrew (author): University of Manchester

Davies, Ioan (author): University of Manchester

Carmeliet, Peter (author): Katholieke Universiteit Leuven

Schwartz, Joan P (author): National Institute of Neurological Disorders and Stroke

Pekna, Marcela, 1966 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology,University of Gothenburg

Kubista, Mikael, 1961 (author): Chalmers tekniska högskola,Chalmers University of Technology

Blomstrand, Fredrik, 1969 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Maragakis, Nicholas (author): Johns Hopkins University

Nilsson, Michael, 1962 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

Pekny, Milos, 1965 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation,University of Gothenburg

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2007-08-29
2008
English.
In: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 28:3, s. 468-81

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Journal article (peer-reviewed)

Abstract Subject headings

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 (ET(B)R) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-)Vim(-/-) astrocytes. In WT astrocytes, ET(B)R 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, ET(B)R-mediated control of gap junctions, and PAI-1 expression.

Keyword

Animals
Astrocytes
pathology
physiology
Brain Ischemia
metabolism
pathology
Gap Junctions
Glial Fibrillary Acidic Protein
deficiency
Glutamic Acid
metabolism
Mice
Mice
Knockout
Middle Cerebral Artery
Plasminogen Activator Inhibitor 1
genetics
Receptor
Endothelin B
analysis
Vimentin
deficiency
Glial Fibrillary Acidic Protein

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Protective role of reactive astrocytes in brain ischemia.

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