title: Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.
abstract: Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Yali
authors: 0000-0002-6311-8757
authors: Y
authors: Xu
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Hai
authors: H
authors: Cui
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Qiong
authors: Q
authors: Zhu
authors: Department of Ultrasound, Southwest Hospital, The Third Military Medical University, Chongqing 400038, China.
authors: Xing
authors: X
authors: Hua
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Hongmei
authors: H
authors: Xia
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Kaibin
authors: K
authors: Tan
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Yunhua
authors: Y
authors: Gao
authors: Department of Ultrasound, Sichuan Provincial Hospital for Women and Children, Chengdu, Sichuan 610000, China.
authors: Jing
authors: J
authors: Zhao
authors: Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, 183 Xinqiao Street, Chongqing 400037, China.
authors: Zheng
authors: 0000-0001-8809-7860
authors: Z
authors: Liu
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D008297:Male; D045423:Microbubbles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013701:Temporal Bone / Q000000981:diagnostic imaging / Q000378:metabolism; D014463:Ultrasonography / Q000379:methods