Limits...
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 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.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

(A) Effect of MCA occlusion on CBF in C57BL/6 mice and  in IRF-1−/−. CBF was measured by laser-Doppler flowmetry in the cerebral cortex of anesthetized artificially ventilated mice (n = 5–8/group)  with monitoring of arterial pressure and controlled arterial blood gases  (see Materials and Methods for details). CBF recordings were made in the  center of the ischemic territory, both where the CBF reduction was  greatest (core) and toward the edge of the ischemic area (periphery).  MCA occlusion produces reduction in CBF that are comparable in  C57BL/6 and in IRF-1−/− mice in both the ischemic core and the periphery (P > 0.05). (B) Mean arterial pressure in wild-type and IRF-1−/−  mice before and after MCA occlusion. No significant differences in arterial pressure were observed (P > 0.05).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2192924&req=5

Figure 6: (A) Effect of MCA occlusion on CBF in C57BL/6 mice and in IRF-1−/−. CBF was measured by laser-Doppler flowmetry in the cerebral cortex of anesthetized artificially ventilated mice (n = 5–8/group) with monitoring of arterial pressure and controlled arterial blood gases (see Materials and Methods for details). CBF recordings were made in the center of the ischemic territory, both where the CBF reduction was greatest (core) and toward the edge of the ischemic area (periphery). MCA occlusion produces reduction in CBF that are comparable in C57BL/6 and in IRF-1−/− mice in both the ischemic core and the periphery (P > 0.05). (B) Mean arterial pressure in wild-type and IRF-1−/− mice before and after MCA occlusion. No significant differences in arterial pressure were observed (P > 0.05).

Mentions: In these studies we investigated whether the reduction in CBF produced by MCA occlusion was comparable in IRF-1−/− mice and controls. As illustrated in Fig. 6 A, the reduction in CBF produced by MCA occlusion in IRF-1−/− mice was not different from that observed in C57BL/6 (P > 0.05; n = 5–8/ group). Similarly, systemic arterial pressure did not differ between IRF-1−/− mice and controls (Fig. 6 B). We then studied the reactivity of the cerebral circulation to systemic hypercapnia in IRF-1−/− mice. The increase in CBF produced by hypercapnia (arterial pC02 = 50–60 mmHg) was 73 ± 12% of control in C57BL/6 and 61 ± 8% in IRF-1−/− mice (P > 0.05; n = 5/group). Thus, the degree of CBF reduction produced by MCA occlusion and the reactivity of the cerebral circulation to hypercapnia are not significantly altered in IRF-1−/− mice.


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)

(A) Effect of MCA occlusion on CBF in C57BL/6 mice and  in IRF-1−/−. CBF was measured by laser-Doppler flowmetry in the cerebral cortex of anesthetized artificially ventilated mice (n = 5–8/group)  with monitoring of arterial pressure and controlled arterial blood gases  (see Materials and Methods for details). CBF recordings were made in the  center of the ischemic territory, both where the CBF reduction was  greatest (core) and toward the edge of the ischemic area (periphery).  MCA occlusion produces reduction in CBF that are comparable in  C57BL/6 and in IRF-1−/− mice in both the ischemic core and the periphery (P > 0.05). (B) Mean arterial pressure in wild-type and IRF-1−/−  mice before and after MCA occlusion. No significant differences in arterial pressure were observed (P > 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: (A) Effect of MCA occlusion on CBF in C57BL/6 mice and in IRF-1−/−. CBF was measured by laser-Doppler flowmetry in the cerebral cortex of anesthetized artificially ventilated mice (n = 5–8/group) with monitoring of arterial pressure and controlled arterial blood gases (see Materials and Methods for details). CBF recordings were made in the center of the ischemic territory, both where the CBF reduction was greatest (core) and toward the edge of the ischemic area (periphery). MCA occlusion produces reduction in CBF that are comparable in C57BL/6 and in IRF-1−/− mice in both the ischemic core and the periphery (P > 0.05). (B) Mean arterial pressure in wild-type and IRF-1−/− mice before and after MCA occlusion. No significant differences in arterial pressure were observed (P > 0.05).
Mentions: In these studies we investigated whether the reduction in CBF produced by MCA occlusion was comparable in IRF-1−/− mice and controls. As illustrated in Fig. 6 A, the reduction in CBF produced by MCA occlusion in IRF-1−/− mice was not different from that observed in C57BL/6 (P > 0.05; n = 5–8/ group). Similarly, systemic arterial pressure did not differ between IRF-1−/− mice and controls (Fig. 6 B). We then studied the reactivity of the cerebral circulation to systemic hypercapnia in IRF-1−/− mice. The increase in CBF produced by hypercapnia (arterial pC02 = 50–60 mmHg) was 73 ± 12% of control in C57BL/6 and 61 ± 8% in IRF-1−/− mice (P > 0.05; n = 5/group). Thus, the degree of CBF reduction produced by MCA occlusion and the reactivity of the cerebral circulation to hypercapnia are not significantly altered in IRF-1−/− mice.

Bottom Line: 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.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