The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 ± 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 ± 3% in IRF-1+/− and by 46 ± 9% in IRF-1−/− mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.
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15 February 1999
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February 15 1999
The Transcription Factor Interferon Regulatory Factor 1 Is Expressed after Cerebral Ischemia and Contributes to Ischemic Brain Injury
Costantino Iadecola,
Costantino Iadecola
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Cindy A. Salkowski,
Cindy A. Salkowski
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Fangyi Zhang,
Fangyi Zhang
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Tracy Aber,
Tracy Aber
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Masao Nagayama,
Masao Nagayama
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Stefanie N. Vogel,
Stefanie N. Vogel
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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M. Elizabeth Ross
M. Elizabeth Ross
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
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Costantino Iadecola
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Cindy A. Salkowski
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Fangyi Zhang
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Tracy Aber
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Masao Nagayama
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Stefanie N. Vogel
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
M. Elizabeth Ross
From the *Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the ‡Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Address correspondence to Costantino Iadecola, Department of Neurology, University of Minnesota, Box 295 UMHC, 420 Delaware St. South-East, Minneapolis, MN 55455. Phone: 612-624-1902; Fax: 612-625-7950; E-mail: [email protected]
The excellent editorial assistance of Ms. Karen MacEwan is acknowledged. We wish to thank Ms. Diana Miller for technical assistance.
Received:
October 19 1998
Revision Received:
December 08 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (4): 719–727.
Article history
Received:
October 19 1998
Revision Received:
December 08 1998
Citation
Costantino Iadecola, Cindy A. Salkowski, Fangyi Zhang, Tracy Aber, Masao Nagayama, Stefanie N. Vogel, M. Elizabeth Ross; The Transcription Factor Interferon Regulatory Factor 1 Is Expressed after Cerebral Ischemia and Contributes to Ischemic Brain Injury . J Exp Med 15 February 1999; 189 (4): 719–727. doi: https://doi.org/10.1084/jem.189.4.719
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