Efficacy of sonothrombolysis in a rat model of embolic ischemic stroke

Neurosci Lett. 2004 May 6;361(1-3):115-9. doi: 10.1016/j.neulet.2004.02.003.

Abstract

The key goal in the treatment of acute ischemic stroke is fast vessel recanalization. Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is efficient in humans but mean time for recanalization is within hours. Ultrasound bio-effects has been shown to facilitate rt-PA mediated thrombolysis in peripheral arteries. We used an embolic stroke model in the rat. In all rats we induced an ischemic stroke by a selective occlusion of the middle cerebral artery with whole blood clots. From an entire collective of 54 rats 47 completed the protocol (n = 7 died early). Four different groups (no treatment n = 6; full dose rt-PA treatment only [10 mg/kg per body weight] n = 14, half dose rt-PA treatment plus ultrasound n = 10, and full dose rt-PA treatment plus ultrasound n = 17) were investigated. We found a significant reduction of absolute as well as relative infarct volume in the full dose rt-PA plus ultrasound group (81+/-72 mm(3); P< 0.05) in comparison to untreated rats (253+/-159 mm(3); P < 0.05) as well as in comparison to rats treated with full dose rt-PA only (167+/-91 mm(3); P < 0.05). There were five intracranial bleedings giving a bleeding rate of 9.3%. In summary: ultrasound treatment in addition to rt-PA is more effective than single rt-PA treatment in reducing infarct volume and safe with regard to bleeding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Combined Modality Therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / physiopathology
  • Hypoxia-Ischemia, Brain / therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / prevention & control
  • Infarction, Middle Cerebral Artery / therapy*
  • Postoperative Hemorrhage / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Recombinant Fusion Proteins / pharmacology
  • Thrombolytic Therapy / methods*
  • Thrombolytic Therapy / trends
  • Tissue Plasminogen Activator / pharmacology
  • Treatment Outcome
  • Ultrasonic Therapy / methods*
  • Ultrasonic Therapy / trends

Substances

  • Recombinant Fusion Proteins
  • Tissue Plasminogen Activator