title: Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism-Induced Acute Ischemic Stroke.
abstract: Microthrombi originating from disintegrated clots or formed in situ may account for the poor clinical improvement of acute ischemic stroke after recanalization therapy. We attempted to determine whether microbubble-mediated sonothrombolysis could dissolve platelet-rich and erythrocyte-rich microthrombi, thereby reducing their brain injury-causing potential.
  
  
  
  Platelet- and erythrocyte-rich microthrombosis were induced by periadventitial application of 5% ferric chloride or thrombin to mesenteric microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by intracarotid injection of platelet- or erythrocyte-rich microthrombi in another 50 rats. Rats were randomly divided into control (CON), ultrasound (US), ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel recanalization rates, cerebral infarct volumes, and neurological scores were determined.
  
  
  
  The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (P<0.05), and the cerebral infarct volumes and neurological scores of rats with either microthrombi were lower in the US+MB group than in the CON group (P<0.01). The infarct volumes and neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r-tPA groups after treatment of rats with platelet-rich microthrombi (P<0.05). In contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct volumes and neurological scores were similar in the r-tPA and US+MB groups, but smaller in the US+MB+r-tPA group (P<0.05).
  
  
  
  Microbubble-mediated sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic stroke. Thus, this method may serve as an attractive adjunct to recanalization therapy for acute ischemic stroke.
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Junfen
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Ruizhu
authors.initials: R
authors.lastname: Huang
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Gangbin
authors.initials: G
authors.lastname: Chen
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Lintao
authors.initials: L
authors.lastname: Zhong
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Shuxin
authors.initials: S
authors.lastname: Shen
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Chuanxi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Shiping
authors.initials: S
authors.lastname: Cao
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Wangjun
authors.initials: W
authors.lastname: Liao
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.).
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.affiliation: From the State Key Laboratory of Organ Failure Research, Department of Cardiology (Y. Lu, J.W., R.H., G.C., L.Z., S.S., C.Z., X.L., S.C., Y. Liao, J.B.) and Department of Oncology (W.L.), Nanfang Hospital, Southern Medical University, Guangzhou, China; and Department of Cardiology, the 458th Hospital of the Chinese People's Liberation Army, Guangzhou, China (R.H.). jianpingbin@126.com jianpingbin@hotmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D020767:Intracranial Thrombosis / Q000150:complications / Q000000981:diagnostic imaging / Q000628:therapy*; D061185:Mechanical Thrombolysis / Q000379:methods*; D045423:Microbubbles / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: microbubbles; stroke; thrombolytic therapy; thrombus; ultrasonics