Low-Power 2-MHz Pulsed-Wave Transcranial Ultrasound Reduces Ischemic Brain Damage in Rats
- 115 Downloads
It is largely unknown whether prolonged insonation with ultrasound impacts the ischemic brain tissue by itself. Our goal was to evaluate safety and the effect of high-frequency ultrasound on infarct volume in rats. Thirty-two Long–Evans rats with permanent middle cerebral and carotid artery occlusions received either 2-MHz ultrasound at two levels of insonation power (128 or 10 mW) or no ultrasound (controls). We measured cerebral hemorrhage, indirect and direct infarct volume as well as edema volume at 24 h. No cerebral hemorrhages were detected in all animals. Exposure to low-power (10 mW) ultrasound resulted in a significantly decreased indirect infarct volume (p = 0.0039), direct infarct volume (p = 0.0031), and brain edema volume (p = 0.01) compared with controls. High-power (128 mW) ultrasound had no significant effects. An additional experiment with India ink showed a greater intravascular penetration of dye into ischemic tissues exposed to low-power ultrasound. Insonation with high-frequency, low-power ultrasound reduces ischemic brain damage in rat. Its effect on edema reduction and possible promotion of microcirculation could be used to facilitate drug and nutrient delivery to ischemic areas.
KeywordsCerebral ischemia Transcranial ultrasound Brain edema reduction Microcirculation
Andrei Alexandrov was supported by the NINDS grants 1K23NS02229-01 and 1P50NS044227, served as PI of the CLOTBUST trial, and currently serves on the Scientific Advisory Board of Cerevast Therapeutics, Inc. Drs Alexandrov, Alexandrov, and Aronowski are co-inventors of the patent: “Therapeutic Methods and Apparatus for Use of Sonication to Enhance Perfusion of Tissue”. US patent # 6,733,450 (May 11, 2004); Assignee: Texas Systems, Board of Reagents. The patent is licensed to Cerevast Therapeutics, Inc.
- 7.Saguchi T, Onoue H, Urashima M, Ishibashi T, Abe T, Furuhata H. Effective and safe conditions of low-frequency transcranial ultrasound thrombolysis for acute ischemic stroke. Neurologic and histologic evaluation in a rat middle cerebral artery stroke model. Stroke. 2008;39:1007–11.PubMedCrossRefGoogle Scholar
- 19.US National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No 85–23, revised 1996)Google Scholar
- 26.Grolimund P. Transmission of ultrasound through the temporal bone. In: Aaslid R, editor. Transcranial Doppler sonography. Wien: Springer; 1986. p. 10–21.Google Scholar
- 32.Davics PF. Flow-mediated endothelial mechanotransduction. Physiol Rev. 1995;75:519–60.Google Scholar