Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation

Abstract

// Wei-Shen Su 1, * , Min-Lan Tsai 2, * , Sin-Luo Huang 1 , Shing-Hwa Liu 3, 4 , Feng-Yi Yang 1, 5, 6 1 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan 2 Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan 3 Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan 4 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 5 Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan 6 Biomedical Engineering Research and Development Center, National Yang-Ming University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Feng-Yi Yang, e-mail: fyyang@ym.edu.tw Shing-Hwa Liu, e-mail: shinghwaliu@ntu.edu.tw Keywords: low intensity ultrasound, permeability, blood-brain barrier, edema, brain injury Received: July 12, 2015      Accepted: October 05, 2015      Published: October 16, 2015 ABSTRACT It has been shown that the blood-brain barrier (BBB) can be locally disrupted by focused ultrasound (FUS) in the presence of microbubbles (MB) while sustaining little damage to the brain tissue. Thus, the safety issue associated with FUS-induced BBB disruption (BBBD) needs to be investigated for future clinical applications. This study demonstrated the neuroprotective effects induced by low-intensity pulsed ultrasound (LIPUS) against brain injury in the sonicated brain. Rats subjected to a BBB disruption injury received LIPUS exposure for 5 min after FUS/MB application. Measurements of BBB permeability, brain water content, and histological analysis were then carried out to evaluate the effects of LIPUS. The permeability and time window of FUS-induced BBBD can be effectively modulated with LIPUS. LIPUS also significantly reduced brain edema, neuronal death, and apoptosis in the sonicated brain. Our results show that brain injury in the FUS-induced BBBD model could be ameliorated by LIPUS and that LIPUS may be proposed as a novel treatment modality for controllable release of drugs into the brain.