Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Ultrasound Med Biol. 2012 Jul;38(7):1234-43. doi: 10.1016/j.ultrasmedbio.2012.02.019.
To investigate whether ultrasound-targeted microbubble destruction (UTMD) could transfer gene into central nervous system (CNS) following blood-brain barrier disruption (BBBD), DNA-loaded microbubbles were infused into the mice intravenously following ultrasonic exposure. Opening of the BBB, changes of mRNA and expression of enhanced green fluorescent protein (EGFP), and safety evaluation were measured. By UTMD, EGFP were substantially expressed in the cytoplasm of the neurons at the sonicated area with minor erythrocytes extravasation and the mRNA and expression of EGFP were markedly enhanced by about 15-fold and 10-fold, respectively, than that with US alone (p < 0.01). No EGFP was detected in the mice treated with DNA-loaded microbubbles or plasmid alone. The gene expression reached a climax at 48 h, gradually reduced to a much lower level thereafter. These results demonstrated UTMD could effectively enhance exogenous gene delivery and expression in CNS following BBBD, and this technique may provide a new method for CNS gene therapy.
为了研究超声靶向微泡破坏（UTMD）是否可以在血脑屏障破坏（BBBD）后将基因转移到中枢神经系统（CNS），在超声暴露后将负载 DNA 的微泡经静脉注入小鼠体内。测量了 BBB 的开放、mRNA 的变化和增强型绿色荧光蛋白（EGFP）的表达以及安全性评估。通过 UTMD，在超声处理区域的神经元细胞质中大量表达 EGFP，只有少量红细胞渗出，并且 EGFP 的 mRNA 和表达分别比单独使用 US 增强了约 15 倍和 10 倍（p < 0.01）。单独用负载 DNA 的微泡或质粒处理的小鼠中未检测到 EGFP。基因表达在 48 小时达到高峰，此后逐渐降低到低得多的水平。这些结果表明，UTMD 可以有效地增强 BBBD 后 CNS 中外源基因的传递和表达，该技术可能为 CNS 基因治疗提供一种新方法。
