Department of Bio and Brain Engineering, KI for the BioCentury, and Optical BioImaging Center, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Proc Natl Acad Sci U S A. 2011 May 31;108(22):9256-61. doi: 10.1073/pnas.1018790108. Epub 2011 May 16.
Systemic delivery of bioactive molecules in the CNS is hampered by the blood-brain barrier, which has bottlenecked noninvasive physiological study of the brain and the development of CNS drugs. Here we report that irradiation with an ultrashort pulsed laser to the blood vessel wall induces transient leakage of blood plasma without compromising vascular integrity. By combining this method with a systemic injection, we delivered target molecules in various tissues, including the brain cortex. This tool allows minimally invasive local delivery of chemical probes, nanoparticles, and viral vectors into the brain cortex. Furthermore, we demonstrated astrocyte-mediated vasodilation in vivo without opening the skull, using this method to load a calcium indicator in conjunction with label-free photoactivation of astrocytes.
血脑屏障阻碍了生物活性分子在中枢神经系统中的系统性传递，这也阻碍了对大脑的非侵入性生理研究和中枢神经系统药物的发展。在这里，我们报告称，用超短脉冲激光辐照血管壁会引起血浆的瞬时渗漏，而不会损害血管完整性。我们将这种方法与系统注射相结合，将目标分子递送到包括大脑皮层在内的各种组织中。该工具允许将化学探针、纳米颗粒和病毒载体等以微创的方式递送到大脑皮层。此外，我们还证明了使用这种方法无需打开颅骨，即可在体内实现星形胶质细胞介导的血管扩张，从而将钙指示剂与星形胶质细胞的无标记光激活相结合进行负载。
