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期刊论文

Postischemic IGF-1 gene transfer promotesneurovascular regeneration after experimentalstroke

杨国源Wei Zhu Yongfeng Fan Qi Hao Fanxia Shen Tomoki Hashimoto Guo-Yuan YangMehdi Gasmi Raymond T Bartus William L Young and Yongmei Chen

Journal of Cerebral Blood Flow & Metabolism (2009)29, 1528-1537,-0001,():

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摘要/描述

Promoting neural regeneration after cerebral infarction has emerged as a potential approach for thetreatment of stroke. Insulin-like growth factor 1 (IGF-1) possesses both neurotrophic and angiogenicproperties. The aim of this study was to determine whether postischemic gene transfer of IGF-1enhances neurovascular regeneration in a mouse model of permanent focal cerebral ischemia.Long-term cerebral IGF-1 overexpression was achieved with adeno-associated viral vector (AAV) bystereotaxic injection at 24 h after a stroke. Adeno-associated viral vector-green fluorescent protein(GFP) or saline was injected as a control. The success of postischemic gene transduction wasconfirmed by a strong GFP signal and by increased IGF-1 protein expression in the peri-infarctregion. Postischemic gene transfer of IGF-1 significantly enhanced vascular density at 8 weeks aftera stroke in the peri-infarct and injection needle tract area compared with AAV-GFP or salinetreatment, as shown by immunohistochemical staining with the vascular marker lectin. Furthermore,increased vascular density was associated with improved local vascular perfusion. Immunohistochemicalstaining with the neuronal progenitor marker, DCX (doublecortin), and the cell proliferationmarker, BrdU (5-bromo-2-deoxyuridine-5-monophosphate), indicated that AAV-IGF-1 treatmentpotently increased neurogenesis compared with AAV-GFP injection. These data show thatpostischemic treatment of IGF-1 effectively promoted neural and vascular regeneration in thechronic stage of cerebral infarction.

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