title: Low-frequency therapeutic ultrasound with varied duty cycle: effects on the ischemic brain and the inner ear.
abstract: Sonothrombolysis is a promising modality for acute stroke treatment. In vitro data suggest a duty cycle dependence of sonothrombolytic efficacy of low-frequency applications. The aim of our study was to examine its impact on safety issues in a rat model of middle cerebral artery occlusion. Rats were exposed to transcranial 60-kHz ultrasound with varied duty cycles. To determine effects on the inner ear, the acoustic threshold was determined in additional healthy animals (acoustic evoked potentials). A short duty cycle (20%) resulted in significant adverse effects (ischemic volume, hemorrhage, functional outcome), which was not observed in longer duty cycle (80%). Continuous-wave insonation produced high rates of mortality and subarachnoid hemorrhage. Hearing was impaired independent of duty cycle. In conclusion, cerebral side effects may be efficiently reduced by modulation of pulsed parameters, which is in line with data on an improved efficacy with longer duty cycle. However, side effects on the auditory system were found to be independent of parameter settings.
authors.affiliation: Department of Neurology, Justus Liebig University, Giessen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reuter
authors.forename: Julia
authors.initials: J
authors.lastname: Masomi
authors.forename: Holger
authors.initials: H
authors.lastname: Kuntze
authors.forename: Ilka
authors.initials: I
authors.lastname: Fischer
authors.forename: Kai
authors.initials: K
authors.lastname: Helling
authors.forename: Clemens
authors.initials: C
authors.lastname: Sommer
authors.forename: Beat
authors.initials: B
authors.lastname: Alessandri
authors.forename: Axel
authors.initials: A
authors.lastname: Heimann
authors.forename: Tibo
authors.initials: T
authors.lastname: Gerriets
authors.forename: Juergen
authors.initials: J
authors.lastname: Marx
authors.forename: Oliver
authors.initials: O
authors.lastname: Kempski
authors.forename: Max
authors.initials: M
authors.lastname: Nedelmann
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000528:radiation effects*; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D007758:Ear, Inner / Q000503:physiopathology* / Q000528:radiation effects*; D006311:Hearing Disorders / Q000209:etiology* / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014464:Ultrasonic Therapy / Q000009:adverse effects*