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Expression of proteins important in central nervous system radiation injury and blood-brain barrier disruption: A key role for hypoxia and HIF1-target genes
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Expression of proteins important in central nervous system radiation injury and blood-brain barrier disruption: A key role for hypoxia and HIF1-target genes
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Dissertation
Expression of proteins important in central nervous system radiation injury and blood-brain barrier disruption: A key role for hypoxia and HIF1-target genes
2002
Overview
Radiation therapy is one of the main modalities in cancer treatment. However, central nervous system damage can occur following radiation for tumors within or near the brain and spinal cord. This is a key toxicity that greatly limits the radiation dose. Blood-brain barrier breakdown and endothelial cell death are characteristic, and this suggests a role for the vascular permeability factor/vascular endothelial growth factor (VEGF). VEGF was upregulated in areas of hypoxia, barrier disruption, necrosis, and expression of another hypoxia-responsive gene, glucose transporter-1. Cells responding to hypoxia by expression of hypoxia-inducible factor-1α (HIF1α) were identified, and the dose response and time course of expression of HIF1α and HIF1-target genes was compared. Transgenic mice with altered VEGF demonstrated a distinct functional outcome following spinal cord irradiation, providing further evidence of the significance of VEGF. Future experiments include investigation of VEGF and downstream molecules mediating radiation-induced permeability changes as potential targets for neuroprotection.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
0612740560, 9780612740563
