Cited by 505Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementNeuroprotection in Cerebral Ischemia

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Protective Role of Reactive Astrocytes in Brain Ischemia

Li, Lizhen, Lundkvist, Andrea, Andersson, Daniel, Wilhelmsson, Ulrika, Nagai, Nobuo, Pardo, Andrea C, Nodin, Christina, Ståhlberg, Anders, Aprico, Karina, Larsson, Kerstin, Yabe, Takeshi, Moons, Lieve, Fotheringham, Andrew, Davies, Ioan, Carmeliet, Peter, Schwartz, Joan P, Pekna, Marcela, Kubista, Mikael, Blomstrand, Fredrik, Maragakis, Nicholas, Nilsson, Michael, Pekny, Milos·2008·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/sj.jcbfm.9600546

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Abstract

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-…

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Authors: Li, L., Lundkvist, A., Andersson, D., Wilhelmsson, U., Nagai, N., Pardo, A. C., Nodin, C., Ståhlberg, A., Aprico, K., Larsson, K., Yabe, T., Moons, L., Fotheringham, A., Davies, I., Carmeliet, P., Schwartz, J. P., Pekna, M., Kubista, M., Blomstrand, F., Maragakis, N., Nilsson, M., & Pekny, M.
Affiliations: University of Gothenburg (SE)
KU Leuven (BE)
Johns Hopkins University (US)
Tataa Biocenter (Sweden) (SE)
Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology at Sahlgrenska Academy, Göteborg University, Göteborg, Sweden
National Institutes of Health (US)
University of Manchester (GB)
Corresponding author: Pekny, Milos
ORCID: Andersson, Daniel
Wilhelmsson, Ulrika
Pardo, Andrea C
Ståhlberg, Anders
Larsson, Kerstin
Yabe, Takeshi
Moons, Lieve
Carmeliet, Peter
Pekna, Marcela
Kubista, Mikael
Maragakis, Nicholas
Nilsson, Michael
Pekny, Milos
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2007-08-29
Volume: 28
Issue: 3
Pages: 468-481
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1038/sj.jcbfm.9600546
OpenAlex: W1999495459
Cited by: 505
References: 43
Citations by year: 2026: 6 · 2025: 13 · 2024: 19 · 2023: 23 · 2022: 19 · 2021: 31 · 2020: 24 · 2019: 34 · 2018: 34 · 2017: 30 · 2016: 34 · 2015: 35 · 2014: 46 · 2013: 28 · 2012: 35
FWCI: 13.10
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed (publishedVersion)
Lirias (submittedVersion)
Chalmers Publication Library (Chalmers University of Technology) (submittedVersion)
Chalmers Research (Chalmers University of Technology) (submittedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords: reactive astrocytes, cerebral ischemia, ischemic penumbra, glial fibrillary acidic protein, vimentin, intermediate filaments, endothelin B receptor, endothelin-3, gap junctions, GLT-1, glutamate uptake, plasminogen activator inhibitor-1, infarct size, middle cerebral artery occlusion, reactive gliosis
MeSH terms: Animals, Astrocytes, Brain Ischemia, Glial Fibrillary Acidic Protein, Vimentin, Plasminogen Activator Inhibitor 1, Gap Junctions, Mice, Knockout, Glutamic Acid, Middle Cerebral Artery, Receptor, Endothelin B, Mice

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Protective Role of Reactive Astrocytes in Brain Ischemia

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