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

Dezhi Mu; Xiangning Jiang; R.Ann Sheldon; Christine K Fox; Shannon E.G Hamrick; Zinaida S Vexler; Donna M Ferriero

Neurobiology of Disease (Dec 2003)

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

Dezhi Mu,
Xiangning Jiang,
R.Ann Sheldon,
Christine K Fox,
Shannon E.G Hamrick,
Zinaida S Vexler,
Donna M Ferriero

Affiliations

Dezhi Mu: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Xiangning Jiang: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
R.Ann Sheldon: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Christine K Fox: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Shannon E.G Hamrick: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Zinaida S Vexler: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
Donna M Ferriero: Department of Neurology, University of California San Francisco, San Francisco, CA, USA; Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

Journal volume & issue: Vol. 14, no. 3
pp. 524 – 534

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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