title: Attenuation of cerebral ischemic injury in interferon regulatory factor 3-deficient rat.
abstract: Interferon regulatory factor 3 (IRF3) is a transcription factor that plays a central role in the innate immune response, apoptosis, and oncogenesis. Previous studies have shown that endogenous IRF3 does not affect stroke in mice; however, paradoxically, elevated IRF3 expression was observed in the rat brains following cerebral ischemia/reperfusion (I/R) injury, indicating that IRF3 may have different functions during stroke in rats than in mice. A clear and comprehensive study of the effect of IRF3 on stroke in rats has been hampered by the lack of an IRF3-knockout rat strain. In this study, a novel IRF3 knockout rat strain and a transgenic rat strain with neuronal-specific IRF3 over-expression (IRF3-TG) were created. Subsequently, the generated IRF3-knockout rats, the neuronal-specific IRF3 over-expressing rats and their corresponding controls were subjected to transient middle cerebral artery occlusion and followed by reperfusion, to investigate the exact role of IRF3 in cerebral I/R in rats. In contrast to the results in mice, IRF3 deficiency in rats provided significant protection against cerebral I/R injury and inhibited neuronal apoptosis, inflammation, and oxidative stress after cerebral I/R injury; the opposite patterns were observed in neuronal-specific IRF3 over-expressing rats. Taken together, these data demonstrate that IRF3 plays a negative regulatory role in cerebral I/R in rats, and IRF3 may be an attractive therapeutic target for preventing stroke. In the present study, we discovered that the transcription factor IRF3, which plays a central role in the innate immune response, apoptosis, and oncogenesis, could exacerbate cerebral ischemia/reperfusion (I/R) injury via activating caspase-dependent neuronal apoptosis, inducing inflammation and oxidative stress. These findings suggest that IRF3 may be an attractive therapeutic target for the prevention of stroke.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.|College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Ankang
authors.initials: A
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.|Animal Experiment Center/Animal Biosafety Level-III Laboratory, Wuhan University, Wuhan, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
keywords: IRF3; apoptosis; inflammation; knockout rat; oxidative stress; stroke