Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat

Abstract Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45...

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Main Authors: Tsong-Hai Lee, Jih-Chao Yeh, Chih-Hung Tsai, Jen-Tsung Yang, Shyh-Liang Lou, Chen-June Seak, Chao-Yung Wang, Kuo-Chen Wei, Hao-Li Liu
Format: Article
Language:English
Published: Nature Portfolio 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-01769-2
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author Tsong-Hai Lee
Jih-Chao Yeh
Chih-Hung Tsai
Jen-Tsung Yang
Shyh-Liang Lou
Chen-June Seak
Chao-Yung Wang
Kuo-Chen Wei
Hao-Li Liu
author_facet Tsong-Hai Lee
Jih-Chao Yeh
Chih-Hung Tsai
Jen-Tsung Yang
Shyh-Liang Lou
Chen-June Seak
Chao-Yung Wang
Kuo-Chen Wei
Hao-Li Liu
author_sort Tsong-Hai Lee
collection DOAJ
description Abstract Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50–63% in groups E and F, to 67–83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.
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spelling doaj.art-d12ec1f03e28435994faa940938b6daa2022-12-21T20:35:51ZengNature PortfolioScientific Reports2045-23222017-05-017111110.1038/s41598-017-01769-2Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in ratTsong-Hai Lee0Jih-Chao Yeh1Chih-Hung Tsai2Jen-Tsung Yang3Shyh-Liang Lou4Chen-June Seak5Chao-Yung Wang6Kuo-Chen Wei7Hao-Li Liu8Stroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityStroke Center and Department of Neurology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityDepartments of Electrical Engineering, Graduate Institute of Clinical Medical Sciences, Chang-Gung UniversityDepartment of Neurosurgery, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityDepartment of Biomedical Engineering, Chung Yuan Christian UniversityDepartment of Emergency Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityDepartment of Cardiology, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityDepartment of Neurosurgery, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung UniversityDepartments of Electrical Engineering, Graduate Institute of Clinical Medical Sciences, Chang-Gung UniversityAbstract Combination therapy with focused ultrasound (FUS) and a neuroprotective agent, BNG-1, was examined in an acute carotid thrombotic occlusion model using LED irradiation in rat to improve the thrombolytic effect of rt-PA. Seven treatment groups included (A) intravenous bolus injection of 0.45 mg/kg rt-PA, (B) intravenous bolus injection of 0.9 mg/kg, (C) sonothrombolysis with FUS alone, (D) oral administration of 2 g/kg BNG-1 for 7 days alone, (E) A + D, (F) A + C, and (G) A + C + D. Four comparison groups were made including (H) 0.45 mg/kg rt-PA 20% bolus +80% IV fusion + FUS, (I) 0.9 mg/kg rt-PA with 10% bolus + 90% intravenous fusion, (J) B + C, (K) B + D. At 7 days after carotid occlusion, small-animal carotid ultrasound and 7 T MR angiography showed the recanalization rate of ≤50% stenosis was 50% in group B and 83% in group I, but 0% in groups A and C and 17% in group D. Combination therapy improved recanalization rate to 50–63% in groups E and F, to 67–83% in groups J and K, and to 100% in groups G and H. Our study demonstrated combination therapy with different remedies can be a feasible strategy to improve the thrombolytic effect of rt-PA.https://doi.org/10.1038/s41598-017-01769-2
spellingShingle Tsong-Hai Lee
Jih-Chao Yeh
Chih-Hung Tsai
Jen-Tsung Yang
Shyh-Liang Lou
Chen-June Seak
Chao-Yung Wang
Kuo-Chen Wei
Hao-Li Liu
Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
Scientific Reports
title Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
title_full Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
title_fullStr Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
title_full_unstemmed Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
title_short Improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
title_sort improved thrombolytic effect with focused ultrasound and neuroprotective agent against acute carotid artery thrombosis in rat
url https://doi.org/10.1038/s41598-017-01769-2
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