Targeted gene delivery to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption

被引:76
|
作者
Huang, Qin [1 ,2 ]
Deng, Jinmu [1 ]
Wang, Feng [1 ]
Chen, Song [1 ]
Liu, Yingjiang [2 ]
Wang, Zhibiao [2 ]
Wang, Zhigang [3 ]
Cheng, Yuan [1 ]
机构
[1] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 2, Chongqing 400010, Peoples R China
[2] Chongqing Med Univ, Dept Biomed Engn, Chongqing 400010, Peoples R China
[3] Chongqing Med Univ, Inst Ultrasound Imaging, Affiliated Hosp 2, Chongqing 400010, Peoples R China
基金
中国国家自然科学基金;
关键词
Blood-brain barrier; Central nervous system; Gene therapy; Focused ultrasound; Microbubbles; Magnetic resonance imaging; NEUROTROPHIC FACTOR; MICROBUBBLES; DNA;
D O I
10.1016/j.expneurol.2011.10.027
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This study aimed to investigate the feasibility of targeted gene transfer into central nervous system (CNS) by MRI-guided focused ultrasound-induced blood brain barrier (BOB) disruption. Before each sonication, T2-weighted images were obtained to select the target region. Followed by injecting DNA-loaded microbubbles into the tail vein, sonication was performed. The state of local BBB, distribution of plasmid DNA through the opened BBB, the ultrastructural changes of neurons and BDNF expression were detected. The results showed that MRI-guided focused ultrasound (FUS) could accomplish noninvasive, transient, and local BBB disruption, at 1 h after sonication, plasmid DNA across the opened BBB had been internalized into the neurons presenting heterogeneous distribution and numerous transparent vesicles were observed in the cytoplasm of the neurons at the sonicated region, suggesting vesicle-mediated endocytosis. At 48 h after sonication, the expressions of exogenous gene pBDNF-EGFP were observed in the cytoplasm of some neurons, and BDNF expressions were markedly enhanced by the combination of ultrasound and pBDNF-EGFP-loaded microbubbles about 20-fold than that of the control group (P < 0.01). The method by using MRI-guided FUS to induce the local BBB disruption could accomplish effective targeted exogenous gene transfer in CNS. This technique may provide a new option for the treatment of various CNS diseases. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:350 / 356
页数:7
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