The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.
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.
Iadecola
C
C
Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. iadec001@tc.umn.edu
Salkowski
C A
CA
Zhang
F
F
Aber
T
T
Nagayama
M
M
Vogel
S N
SN
Ross
M E
ME
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D007249:Inflammation / Q000235:genetics; D050856:Interferon Regulatory Factor-1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014158:Transcription, Genetic