Thrombolytic effects of a combined therapy with targeted microbubbles and ultrasound in a 6 h cerebral thrombosis rabbit model.
Our previous study has shown that P1 polypeptide-loaded microbubbles (clot-targeted microbubbles, TMB) are effective for thrombolysis and recanalization in a 0.5 h cerebral thrombosis rabbit model when combined with low-frequency ultrasound (LFUS, 0.8 MHz). However, the thrombolytic effects of TMB combined with LFUS are still unclear in a 6 h cerebral thrombosis rabbit model, which closely resembles human embolic stroke. Aiming to extend the 3 h therapeutic window limitation of thrombolytic drugs, a 6 h cerebral thrombosis model of common carotid artery (CCA) occlusion was induced in rabbits, and thrombolysis using TMB by intra-arterial (IA) and intravenous (IV) application combined with LFUS was then compared to untargeted microbubbles (UTMB) and recombinant tissue plasminogen activator (rt-PA). The patency score and thrombolysis in brain ischemia (TIBI) in IA TMB combined with LFUS (IA TMB/LFUS) were significantly higher compared to the IA normal saline control with LFUS (IA SC/LFUS) (both P < 0.05) and IA UTMB plus LFUS (IA UTMB/LFUS) (both P < 0.05), respectively. The recanalization rate in the IA TMB/LFUS group (66.67%) was significantly higher compared to the IA SC/LFUS group (12.50%, P < 0.05). The patency score, TIBI and recanalization rate of IA TMB/LFUS were higher than in the IV TMB/LFUS group, but there was no significant difference between the two groups, which was similar to the infarction ratio. TMB/LFUS is an effective and safe therapy for thrombolysis in a 6 h cerebral thrombosis rabbit model, and the IA TMB/LFUS group was slightly better than the IV TMB/LFUS group.
Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Shu-Ting
ST
Ren
Li-Hui
LH
Long
Mei
M
Wang
Yi-Ping
YP
Li
Hao
H
Qin
Hui
H
Zhang
Bo-Bin
BB
Jing
Ying-Xue
YX
Li
Wei-Jin
WJ
Zang
Bing
B
Wang
Xin-Liang
XL
Shen
D000818:Animals; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D020767:Intracranial Thrombosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D008297:Male; D045423:Microbubbles / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D015912:Thrombolytic Therapy / Q000379:methods*; D014464:Ultrasonic Therapy / Q000379:methods*; D014463:Ultrasonography
D005343:Fibrinolytic Agents