Abstract
Introduction: To evaluate whether both acute and chronic low-intensity pulsed ultrasound (LIPUS) affect brain functions of healthy male and female mice. Methods: Ultrasound (frequency: 1.5 MHz; pulse: 1.0 kHz; spatial average temporal average (SATA) intensity: 25 mW/cm(2); and pulse duty cycle: 20%) was applied at mouse head in acute test for 20 minutes, and in chronic experiment for consecutive 10 days, respectively. Behaviors were then evaluated. Results: Both acute and chronic LIPUS at 25 mW/cm(2) exposure did not affect the abilities of movements, mating, social interaction, and anxiety-like behaviors in the male and female mice. However, physical restraint caused struggle-like behaviors and short-time memory deficits in chronic LIPUS groups in the male mice. Conclusion: LIPUS at 25 mW/cm(2) itself does not affect brain functions, while physical restraint for LIPUS therapy elicits struggle-like behaviors in the male mice. An unbound helmet targeted with ultrasound intensity at 25-50 mW/cm(2) is proposed for clinical brain disease therapy.