The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Protective Role of Reactive Astrocytes in Brain Ischemia
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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In the citing paper
“Attenuated reactive gliosis in Gfap−/− Vim−/− mice was connected with larger infarctions in a mouse model of focal brain ischemia (32) and facilitated disease progression in a mouse model of Batten's disease (33).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [32]
In the citing paper
“Further, the effects of acute central nervous system injury are comparable in Gfap−/−, Vim−/−, and wild-type mice (22, 32).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [32]
In the citing paper
“The intermediate filament proteins GFAP and Vim are expressed at high levels in activated astrocytes and are critical for the activated phenotype.”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [32]
In the citing paper
“Under baseline conditions, however, Gfap−/−Vim−/− mice have astrocytes of normal appearance and grossly normal brain anatomy (22, 23, 32).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [32]
In the citing paper
“But when Gfap and Vim are both deleted, astrocytes cannot form intermediate filament networks or display reactive morphology (22, 23, 32).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [32]
Citations
Cites
Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System
Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., & Frisén, J. (1999) · Cell · doi:10.1016/s0092-8674(00)80956-3 · Cited by 1,875
Reactive astrocytes: cellular and molecular cues to biological function
Ridet, J., Privat, A., Malhotra, S. K., & Gage, F. H. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01139-9 · Cited by 1,766
Localization of neuronal and glial glutamate transporters
Rothstein, J. D., Martin, L. J., Levey, A. I., Dykes‐Hoberg, M., Jin, L., Wu, D. M., Nash, N. R., & Kuncl, R. W. (1994) · Neuron · doi:10.1016/0896-6273(94)90038-8 · Cited by 1,703
Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury
Faulkner, J. R., Herrmann, J. E., Woo, M. J., Tansey, K. E., Doan, N., & Sofroniew, M. V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3547-03.2004 · Cited by 1,652
Molecular profile of reactive astrocytes—Implications for their role in neurologic disease
Eddleston, M., & Mucke, L. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90380-x · Cited by 1,441
Bush, T. G., Puvanachandra, N., Horner, C. H., Polito, A., Ostenfeld, T., Svendsen, C. N., Mucke, L., Johnson, M. H., & Sofroniew, M. V. (1999) · Neuron · doi:10.1016/s0896-6273(00)80781-3 · Cited by 1,116
Okada, S., Nakamura, M., Katoh, H., Miyao, T., Shimazaki, T., Ishii, K., Yamane, J., Yoshimura, A., Iwamoto, Y., Toyama, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1425 · Cited by 991
Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator
Tsirka, S. E., Gualandris, A., Amaral, D. G., & Strickland, S. (1995) · Nature · doi:10.1038/377340a0 · Cited by 658
Liedtke, W., Edelmann, W., Bieri, P. L., Chiu, F.-C., Cowan, N. J., Kucherlapati, R., & Raine, C. S. (1996) · Neuron · doi:10.1016/s0896-6273(00)80194-4 · Cited by 538
Gap-junction-mediated propagation and amplification of cell injury
Lin, J. H.-C., Weigel, H., Cotrina, M. L., Liu, S., Bueno, E., Hansen, A. J., Hansen, T. W., Goldman, S. A., & Nedergaard, M. (1998) · Nature Neuroscience · doi:10.1038/2210 · Cited by 481
Wilhelmsson, U., Li, L., Pekna, M., Berthold, C.-H., Blom, S., Eliasson, C., Renner, O., Bushong, E., Ellisman, M., Morgan, T. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0820-04.2004 · Cited by 455
Self-citationAstrocyte intermediate filaments in CNS pathologies and regeneration
Pekny, M., & Pekna, M. (2004) · The Journal of Pathology · doi:10.1002/path.1645 · Cited by 420
Self-citationProperties of the Reverse Transcription Reaction in mRNA Quantification
Ståhlberg, A., Håkansson, J., Xian, X., Semb, H., & Kubista, M. (2004) · Clinical Chemistry · doi:10.1373/clinchem.2003.026161 · Cited by 409
Self-citationPekny, M., Johansson, C. B., Eliasson, C., Stakeberg, J., Wallén, Å., Perlmann, T., Lendahl, U., Betsholtz, C., Berthold, C.-H., & Frisén, J. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.503 · Cited by 405
Self-citationControl of gap-junctional communication in astrocytic networks
Giaume, C., & McCarthy, K. D. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10046-1 · Cited by 385
Intermediate Filament Protein Partnership in Astrocytes
Eliasson, C., Sahlgren, C., Berthold, C.-H., Stakeberg, J., Celis, J. E., Betsholtz, C., Eriksson, J. E., & Pekny, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.23996 · Cited by 357
Self-citationTargeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology.
McCall, M. A., Gregg, R. G., Behringer, R. R., Brenner, M., Delaney, C. L., Galbreath, E. J., Zhang, C. L., Pearce, R. A., Chiu, S. Y., & Messing, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6361 · Cited by 353
Pekny, M., Levéen, P., Pekna, M., Eliasson, C., Berthold, C. H., Westermark, B., & Betsholtz, C. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07147.x · Cited by 336
Self-citationMenet, V., Prieto, M., Privat, A., & y Ribotta, M. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1533187100 · Cited by 325
Role of glial cells in cerebral ischemia
Nedergaard, M., & Dirnagl, U. (2005) · Glia · doi:10.1002/glia.20205 · Cited by 307
Gomi, H., Yokoyama, T., Fujimoto, K., Ikeda, T., Katoh, A., Itoh, T., & Itohara, S. (1995) · Neuron · doi:10.1016/0896-6273(95)90238-4 · Cited by 256
Role of Plasminogen System Components in Focal Cerebral Ischemic Infarction
Nagai, N., Mol, M. D., LIJNEN, H. R., Carmeliet, P., & Collen, D. (1999) · Circulation · doi:10.1161/01.cir.99.18.2440 · Cited by 251
Self-citationRobust neural integration from retinal transplants in mice deficient in GFAP and vimentin
Kinouchi, R., Takeda, M., Yang, L., Wilhelmsson, U., Lundkvist, A., Pekny, M., & Chen, D. F. (2003) · Nature Neuroscience · doi:10.1038/nn1088 · Cited by 229
Self-citationMitani, A., & Tanaka, K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-18-07176.2003 · Cited by 191
März, P., Heese, K., Dimitriades‐Schmutz, B., Rose‐John, S., & Otten, U. (1999) · Glia · doi:10.1002/(sici)1098-1136(199905)26:3 · Cited by 177
Intermediate filaments regulate astrocyte motility
Lepekhin, E. A., Eliasson, C., Berthold, C., Berezin, V., Bock, E., & Pekny, M. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00595.x · Cited by 164
Self-citationHigh Susceptibility to Cerebral Ischemia in GFAP-Null Mice
Nawashiro, H., Brenner, M., Fukui, S., Shima, K., & Hallenbeck, J. M. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200007000-00003 · Cited by 141
Pekny, M., Stanness, K. A., Eliasson, C., Betsholtz, C., & Janigro, D. (1998) · PubMed · Cited by 135
Self-citationDifferences in the cerebrovascular anatomy of C57Black/6 and SV129 mice
Maeda, K., Hata, R., & Hossmann, K.-A. (1998) · Neuroreport · doi:10.1097/00001756-199805110-00012 · Cited by 127
Conditional Ablation of Cerebellar Astrocytes in Postnatal Transgenic Mice
Delaney, C. L., Brenner, M. J., & Messing, A. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-21-06908.1996 · Cited by 122
Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1G93A mice
Pardo, A. C., Wong, V., Benson, L. M., Dykes, M., Tanaka, K., Rothstein, J. D., & Maragakis, N. J. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.03.028 · Cited by 122
Self-citationGlutamate Transporter Cluster Formation in Astrocytic Processes Regulates Glutamate Uptake Activity
Zhou, J., & Sutherland, M. L. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1404-04.2004 · Cited by 114
Pekny, M., Eliasson, C., Chien, C. L., Kindblom, L. G., Liem, R. K. H., Hamberger, A., & Betsholtz, C. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3922 · Cited by 102
Self-citationNF-?B modulates lipopolysaccharide-induced microglial nerve growth factor expression
Heese, K., Fiebich, B. L., Bauer, J., & Otten, U. (1998) · Glia · doi:10.1002/(sici)1098-1136(199804)22:4 · Cited by 96
Self-citationFibrin‐modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: A review
Sheehan, J. J., & Tsirka, S. E. (2005) · Glia · doi:10.1002/glia.20150 · Cited by 89
Distinct pharmacological properties of ET-1 and ET-3 on astroglial gap junctions and Ca2+signaling
Blomstrand, F., Giaume, C., Hansson, E., & Rönnbäck, L. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.277.4.c616 · Cited by 87
Self-citationDing, M., Eliasson, C., Betsholtz, C., Hamberger, A., & Pekny, M. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00240-x · Cited by 84
Self-citationAnděrová, M., Kubinová, Š., Mazel, T., Chvátal, A., Eliasson, C., Pekny, M., & Syková, E. (2001) · Glia · doi:10.1002/glia.1084 · Cited by 69
Self-citationNAGAI, N., Suzuki, Y., HOEF, B. V., LIJNEN, H. R., & Collen, D. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01466.x · Cited by 65
Self-citationPekny, M., Eliasson, C., Siushansian, R., Ding, M., Dixon, S. J., Pekna, M., Wilson, J. X., & Hamberger, A. (1999) · Neurochemical Research · doi:10.1023/a:1022572304626 · Cited by 62
Self-citationSwelling and Volume Control in Brain Astroglial Cells
Kimelberg, H. K. (1991) · Advances in comparative and environmental physiology · doi:10.1007/978-3-642-76226-0_4 · Cited by 55
Shobha, K., Vijayalakshmi, K., Alladi, P. A., Nalini, A., Sathyaprabha, T. N., & Raju, T. R. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.12.004 · Cited by 52
Oedema and glial cell involvement in the aged mouse brain after permanent focal ischaemia
Fotheringham, A. P., Davies, C. A., & Davies, I. (2000) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2000.00265.x · Cited by 29
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- Kraig R, 1995, Neuroglia, 964
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Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
Molecular dissection of reactive astrogliosis and glial scar formation
Sofroniew, M. V. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.08.002 · Cited by 2,594
Reactive Gliosis and the Multicellular Response to CNS Damage and Disease
Burda, J. E., & Sofroniew, M. V. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.034 · Cited by 1,500
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202
STAT3 is a Critical Regulator of Astrogliosis and Scar Formation after Spinal Cord Injury
Herrmann, J. E., Imura, T., Song, B., Qi, J., Ao, Y., Nguyen, T. K., Korsak, R. A., Takeda, K., Akira, S., & Sofroniew, M. V. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1709-08.2008 · Cited by 958
Metadata
- 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
- 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
- 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
- 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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