Focused Shockwave Induced Blood-Brain Barrier Opening

Abstract

Blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most compounds, and controls the exchange of substances between the blood and the central nervous system (CNS) to maintain the physiological condition. Nonetheless, the protecting mechanism of BBB also prevents CNS drugs from treating CNS disorders effectively. In this study, a commercial focused shockwave was applied for inducing blood-brain barrier opening to improve the efficiency of drugs delivery. A commercial focused shockwave instrument (Piezowave, Richard Wolf GmbH) was combined with a computer controlled bi-axial locator, and four-point laser locator on transducer to process the shockwave induced blood-brain barrier opening. Evans blue was injected via tail vein as a BBB opening indicator. All Brain samples were collected 3 hr after shocking, and analyzed by H&E stain and TUNEL assay (S7100, Millipore). Under intensity level 5 (P- -10 Mpa, P+ 17.4 Mpa, 0.182 mJ/mm2) with 5 Hz of shocking, BBB was opened by 100 times of shocks (with above 50 % of success opening rate), and opened with bleeding by 300 times of shocks. With the proposed locating- mechanism, the target treating area could be located precisely, including the depth and the area on brains (SD rat). The proposed focused shockwave technique to induce blood-brain barrier opening has several advantages: consistent BBB opening rate, good penetration (due to low frequency), lack of thermal effect, and easy-accessibility (based on a commercial device).