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• W2155306535 abstract "Background and Purpose— Exogenous delivery of vascular endothelial growth factor gene (VEGF) may provide a useful approach to the treatment of brain ischemia. We investigated the use of a hypoxia-responsive element to control VEGF expression given for neuroprotection. Methods— Three groups (n=36) of mice received AAVH9-VEGF, AAVH9-lacZ, or saline injection. Five days after gene transfer, the mice underwent 45 minutes of transient middle cerebral artery occlusion (tMCAO) followed by 1 to 7 days of reperfusion. Infarct volume was determined using cresyl violet staining; neuronal injury was examined using TUNEL, cleaved caspase-3, and fluoro-Jade B staining. Results— Hypoxia-inducible factor-1 (HIF-1) was overexpressed after tMCAO in the ischemic hemisphere in the brain. Expression of lacZ, mediated by AAV-lacZ, was seen before and after tMCAO; however, AAVH9-lacZ-mediated lacZ expression was detected only after tMCAO. Infarct volume was smaller in the AAVH9-VEGF-transduced group compared with AAVH9-lacZ and saline groups (55% reduction, P <0.05) with reduced TUNEL (29±5% and 30±7% versus 12±3%, P <0.05), cleaved caspase-3 (20±3% and 21±5% versus 13±4%, P <0.05) and fluoro-Jade B (23±3% and 24±5% versus 12±5%, P <0.05) -positive neurons, respectively. Conclusion— Exogenous expression of VEGF through AAVH9-VEGF gene transfer 5 days before the onset of ischemia provides neuroprotection. Hypoxia-responsive element is a viable strategy of restricting VEGF expression to areas of ischemia to minimize adverse effects of therapy on adjacent normal parenchyma." @default.
• W2155306535 created "2016-06-24" @default.
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• W2155306535 date "2006-10-01" @default.
• W2155306535 modified "2023-10-16" @default.
• W2155306535 title "Adeno-Associated Viral Vector-Mediated Hypoxia-Inducible Vascular Endothelial Growth Factor Gene Expression Attenuates Ischemic Brain Injury After Focal Cerebral Ischemia in Mice" @default.
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• W2155306535 doi "https://doi.org/10.1161/01.str.0000240407.14765.e8" @default.
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