Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model

Stroke is a devastating condition occurring in at least 1 in 4000 live births in the neonatal period. Since hypoxia-inducible factor (HIF)-1α can modulate ischemic injury via induction of target genes that may protect cells against ischemia, and is induced after preconditioning by hypoxia in the neo...

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Main Authors: Dezhi Mu, Xiangning Jiang, R.Ann Sheldon, Christine K Fox, Shannon E.G Hamrick, Zinaida S Vexler, Donna M Ferriero
Format: Article
Language:English
Published: Elsevier 2003-12-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996103001694
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author Dezhi Mu
Xiangning Jiang
R.Ann Sheldon
Christine K Fox
Shannon E.G Hamrick
Zinaida S Vexler
Donna M Ferriero
author_facet Dezhi Mu
Xiangning Jiang
R.Ann Sheldon
Christine K Fox
Shannon E.G Hamrick
Zinaida S Vexler
Donna M Ferriero
author_sort Dezhi Mu
collection DOAJ
description Stroke is a devastating condition occurring in at least 1 in 4000 live births in the neonatal period. Since hypoxia-inducible factor (HIF)-1α can modulate ischemic injury via induction of target genes that may protect cells against ischemia, and is induced after preconditioning by hypoxia in the neonatal rat brain hypoxia-ischemia model, we evaluated whether HIF-1α is induced after focal ischemia-reperfusion, a model for neonatal stroke. We developed an ischemia-reperfusion model in postnatal day 10 (P10) rats by transiently occluding the middle cerebral artery (MCA) for 1.5 h. The MCA territory was reperfused for 0, 4, 8, or 24 h and the expression of HIF-1α and its target gene, vascular endothelial growth factor (VEGF), were delineated. HIF-1α protein and VEGF protein peaked at 8 h, and declined subsequently at 24 h in injured cortex following 1.5 h of MCA occlusion. Double-immunolabeling indicated that both HIF-1α and VEGF are expressed together in neurons with a similar time course of expression. The presence of HIF-1α and VEGF after moderate ischemia-reperfusion injury suggests potential avenues to exploit for neuroprotection.
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spelling doaj.art-dc1d3f55e6cf425697bd3390aef75abe2022-12-21T21:56:32ZengElsevierNeurobiology of Disease1095-953X2003-12-01143524534Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke modelDezhi Mu0Xiangning Jiang1R.Ann Sheldon2Christine K Fox3Shannon E.G Hamrick4Zinaida S Vexler5Donna M Ferriero6Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USADepartment of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USAStroke is a devastating condition occurring in at least 1 in 4000 live births in the neonatal period. Since hypoxia-inducible factor (HIF)-1α can modulate ischemic injury via induction of target genes that may protect cells against ischemia, and is induced after preconditioning by hypoxia in the neonatal rat brain hypoxia-ischemia model, we evaluated whether HIF-1α is induced after focal ischemia-reperfusion, a model for neonatal stroke. We developed an ischemia-reperfusion model in postnatal day 10 (P10) rats by transiently occluding the middle cerebral artery (MCA) for 1.5 h. The MCA territory was reperfused for 0, 4, 8, or 24 h and the expression of HIF-1α and its target gene, vascular endothelial growth factor (VEGF), were delineated. HIF-1α protein and VEGF protein peaked at 8 h, and declined subsequently at 24 h in injured cortex following 1.5 h of MCA occlusion. Double-immunolabeling indicated that both HIF-1α and VEGF are expressed together in neurons with a similar time course of expression. The presence of HIF-1α and VEGF after moderate ischemia-reperfusion injury suggests potential avenues to exploit for neuroprotection.http://www.sciencedirect.com/science/article/pii/S0969996103001694DevelopmentIschemiaBrainToleranceNeuroprotection
spellingShingle Dezhi Mu
Xiangning Jiang
R.Ann Sheldon
Christine K Fox
Shannon E.G Hamrick
Zinaida S Vexler
Donna M Ferriero
Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
Neurobiology of Disease
Development
Ischemia
Brain
Tolerance
Neuroprotection
title Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
title_full Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
title_fullStr Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
title_full_unstemmed Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
title_short Regulation of hypoxia-inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
title_sort regulation of hypoxia inducible factor 1α and induction of vascular endothelial growth factor in a rat neonatal stroke model
topic Development
Ischemia
Brain
Tolerance
Neuroprotection
url http://www.sciencedirect.com/science/article/pii/S0969996103001694
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