title: Controllable permeability of blood-brain barrier and reduced brain injury through low-intensity pulsed ultrasound stimulation.
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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wei-Shen
authors.initials: WS
authors.lastname: Su
authors.affiliation: Department of Pediatrics, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Min-Lan
authors.initials: ML
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sin-Luo
authors.initials: SL
authors.lastname: Huang
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.|Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.|Biomedical Engineering Research and Development Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000628:therapy; D001930:Brain Injuries / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D002199:Capillary Permeability / Q000502:physiology*; D008297:Male; D045423:Microbubbles / Q000009:adverse effects; D009410:Nerve Degeneration / Q000628:therapy; D017207:Rats, Sprague-Dawley; D013010:Sonication / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*; D000069453:Ultrasonic Waves; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water
keywords: blood-brain barrier; brain injury; edema; low intensity ultrasound; permeability