Choi James J, Wang Shougang, Brown Truman R, Small Scott A, Duff Karen E K, Konofagou Elisa E
Department Biomedical Engineering, Columbia University, New York, NY 10027, USA.
Ultrason Imaging. 2008 Jul;30(3):189-200. doi: 10.1177/016173460803000304.
The spatio-temporal nature of focused ultrasound-induced blood-brain barrier (BBB) opening as a brain drug delivery method was investigated in Alzheimer's disease model mice. The left hippocampus of transgenic (APP/PS1, n = 3) and nontransgenic (n = 3) mice was sonicated (frequency: 1.525 MHz, peak-negative pressure: 600 kPa, pulse length: 20 ms, duty cycle: 20%, duration: 1 min) in vivo, through their intact skin and skull, after intravenous injection of microbubbles (SonoVue; 25 microl). Sequential, high-field MR images (9.4 Tesla) were acquired before and after injection of gadolinium (Omniscan, 0.75 ml, molecular weight: 573.7 Da) on two separate days for each mouse. Gadolinium deposits through the ultrasound-induced BBB opening in the left hippocampus revealed significant contrast-enhancement in the MRI. On the following day, MRI revealed significant BBB closure within the same region. However, the BBB opening extent and BBB closing timeline varied in different regions within the same sonicated location. This indicates that opening and closing were dependent on the brain region targeted. No significant difference in BBB opening or closing behaviors was observed between the APP/PS1 and the nontransgenic mice. In conclusion, a BBB-impermeable molecule was noninvasively, transiently and reproducibly delivered to the hippocampus of Alzheimer's APP/PS1 mice.
在阿尔茨海默病模型小鼠中，研究了聚焦超声诱导血脑屏障（BBB）开放作为一种脑内药物递送方法的时空特性。在静脉注射微泡（声诺维；25微升）后，通过完整的皮肤和颅骨对转基因（APP/PS1，n = 3）和非转基因（n = 3）小鼠的左侧海马体进行体内超声处理（频率：1.525兆赫，峰值负压：600千帕，脉冲长度：20毫秒，占空比：20%，持续时间：1分钟）。在每只小鼠的两个不同日期，在注射钆（欧乃影，0.75毫升，分子量：573.7道尔顿）之前和之后采集连续的高场磁共振图像（9.4特斯拉）。钆通过超声诱导的左侧海马体血脑屏障开放沉积，在磁共振成像中显示出显著的对比增强。在接下来的一天，磁共振成像显示同一区域内血脑屏障明显闭合。然而，在同一超声处理部位的不同区域，血脑屏障开放程度和血脑屏障闭合时间线有所不同。这表明开放和闭合取决于靶向的脑区。在APP/PS1小鼠和非转基因小鼠之间，未观察到血脑屏障开放或闭合行为的显著差异。总之，一种血脑屏障不透性分子被无创、短暂且可重复地递送至阿尔茨海默病APP/PS1小鼠的海马体。
