Ultrasonic-induced reversible blood–brain barrier opening: Safety evaluation into the cellular level

Abstract

An important function of the blood–brain barrier (BBB) is to protect the central nervous system and maintain its homeostasis, but it is also a major barrier to the intervention and treatment of neurological diseases. Our study aimed at opening the BBB using a noninvasive method, focused ultrasound, screening for 16 different parameter combinations of frequency, peak voltage (Ppeak) and irradiation time. Comparing the results of hematoxylin–eosin staining, serum oxidative damage factor and TUNEL staining under various conditions, we obtained a parameter combination that did not lead to oxidative stress injury and apoptosis: 0.8 mHz + 900 mVpp + 90 s. It will be used as a safety parameter for BBB opening treatment of Parkinson’s disease in our subsequent experiments. In addition, the closing time after the BBB opening was verified in magnetic resonance imaging contrast examination and at the tissue level. It is worth mentioning that, different from previous studies, we focused on damage assessment at cellular and molecular levels.

Keywords

• focused ultrasound
• blood
• brain barrier
• oxidative stress injury
• reactive oxygen species