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The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.

Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M, Vogel SN, Ross ME - J. Exp. Med. (1999)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. iadec001@tc.umn.edu

ABSTRACT
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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Distribution of the cerebral infarct produced by MCA occlusion in C57BL/6 mice and in IRF-1+/− and IRF-1−/− mice 4 d after  MCA occlusion. Thionin-stained representative sections at three different  rostrocaudal levels of the mouse brain are presented. The pale areas with  asterisks represent the infarcted brain. The infarct size is smaller in IRF-1−/− than in IRF-1+/− or C57BL/6 at all rostrocaudal levels.
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Figure 3: Distribution of the cerebral infarct produced by MCA occlusion in C57BL/6 mice and in IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Thionin-stained representative sections at three different rostrocaudal levels of the mouse brain are presented. The pale areas with asterisks represent the infarcted brain. The infarct size is smaller in IRF-1−/− than in IRF-1+/− or C57BL/6 at all rostrocaudal levels.

Mentions: In these experiments we used mice with a mutation of IRF-1 to determine whether IRF-1 contributes to cerebral ischemic injury. In C57BL/6 mice (n = 6), MCA occlusion produced reproducible infarcts involving mainly the cerebral cortex (Figs. 3 and 4). Size and regional distribution of the infarct were comparable to those previously reported in mice from this and other laboratories (20, 41). The volume of the infarct in IRF-1+/+ mice did not differ from that of C57BL/6 mice (P > 0.05; Fig. 4 A). Infarct volumes in IRF-1 knockout mice were smaller than those observed in C57BL/6 mice (Figs. 3 and 4). The reduction was less pronounced in IRF-1+/− (23 ± 3%; P < 0.05; n = 5), than in IRF-1−/− mice (46 ± 9%; P < 0.05; n = 6), and involved the infarct border throughout the entire rostrocaudal extent of the ischemic lesion (Figs. 3 and 4). The volume of postischemic brain swelling did not differ between C57BL/6 (6.6 ± 0.6 mm3) and IRF-1+/− mice (5.7 ± 0.8; P > 0.05), but was significantly reduced in IRF-1−/− mice (3.5 ± 0.8; P < 0.05).


The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.

Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M, Vogel SN, Ross ME - J. Exp. Med. (1999)

Distribution of the cerebral infarct produced by MCA occlusion in C57BL/6 mice and in IRF-1+/− and IRF-1−/− mice 4 d after  MCA occlusion. Thionin-stained representative sections at three different  rostrocaudal levels of the mouse brain are presented. The pale areas with  asterisks represent the infarcted brain. The infarct size is smaller in IRF-1−/− than in IRF-1+/− or C57BL/6 at all rostrocaudal levels.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192924&req=5

Figure 3: Distribution of the cerebral infarct produced by MCA occlusion in C57BL/6 mice and in IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Thionin-stained representative sections at three different rostrocaudal levels of the mouse brain are presented. The pale areas with asterisks represent the infarcted brain. The infarct size is smaller in IRF-1−/− than in IRF-1+/− or C57BL/6 at all rostrocaudal levels.
Mentions: In these experiments we used mice with a mutation of IRF-1 to determine whether IRF-1 contributes to cerebral ischemic injury. In C57BL/6 mice (n = 6), MCA occlusion produced reproducible infarcts involving mainly the cerebral cortex (Figs. 3 and 4). Size and regional distribution of the infarct were comparable to those previously reported in mice from this and other laboratories (20, 41). The volume of the infarct in IRF-1+/+ mice did not differ from that of C57BL/6 mice (P > 0.05; Fig. 4 A). Infarct volumes in IRF-1 knockout mice were smaller than those observed in C57BL/6 mice (Figs. 3 and 4). The reduction was less pronounced in IRF-1+/− (23 ± 3%; P < 0.05; n = 5), than in IRF-1−/− mice (46 ± 9%; P < 0.05; n = 6), and involved the infarct border throughout the entire rostrocaudal extent of the ischemic lesion (Figs. 3 and 4). The volume of postischemic brain swelling did not differ between C57BL/6 (6.6 ± 0.6 mm3) and IRF-1+/− mice (5.7 ± 0.8; P > 0.05), but was significantly reduced in IRF-1−/− mice (3.5 ± 0.8; P < 0.05).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. iadec001@tc.umn.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus