HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic injury.

作者: Wanqiu Chen , Vikram Jadhav , Jiping Tang , John H. Zhang

DOI: 10.1007/978-3-211-85578-2_77

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摘要: BACKGROUND Hypoxia-inducible-factor-1alpha (HIF-1alpha) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. This study was designed to elucidate role HIF-1alpha neonatal hypoxia-ischemia (HI) brain injury. METHODS 2-methoxyestradiol (2ME2), inhibitor, tested at different dosages (1.5, 15 150 mg/kg) therapeutic window by administrating (15 immediately or 3 hours after induction hypoxic ischemic Infarct size using TTC staining edema were measured 48 post hypoxia-ischemia. Blood-brain barrier (BBB) permeability examined IgG staining. Vascular endothelial growth factor (VEGF) expression distribution studied immunohistochemistry western blotting analysis. FINDINGS 2ME2 exhibited dose-dependent neuroprotection decreasing infarct volume attenuating edema. also attenuated BBB disruption, decreased vascular expression. The neuroprotection, however, lost when administered HI. CONCLUSION shows that acute inhibition is neuroprotective hypoxic-ischemic injury preserving integrity reducing

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