BACKGROUND: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensive rat (SHR) model of permanent MCAO. METHODS: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm(2)) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically. RESULTS: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups. CONCLUSIONS: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensive rats under the undesired permanent MCAO condition.
BACKGROUND: Some studies suggest that low-frequency transcranial ultrasound (LFTUS) can enhance thrombolysis, but other studies suggest that it may have adverse effects on intracranial tissues. We previously reported that LFTUS with appropriate parameters was effective and safe in a normotensive rat model of thromboembolic middle cerebral artery occlusion (MCAO) stroke. The goal of this study was to test the safety of this strategy in a spontaneously hypertensiverat (SHR) model of permanent MCAO. METHODS: Right MCAO was achieved in male SHRs using intraluminal nylon sutures. Rats exhibiting left hemiparesis were randomly assigned to one of four different groups: (1) normal saline (NS) group (n = 8), intravenous administration of NS as placebo at 3 h after MCAO; (2) NS+LFTUS group (n = 10), NS administration with simultaneous application of LFTUS (480.4 kHz, continuous wave, at an intensity of 0.3 W/cm(2)) for 1 h; (3) tissue plasminogen activator (tPA) group (n = 11), intravenous administration of alteplase (10 mg/kg body weight) over 1 h instead of NS; or (4) tPA+LFTUS group (n = 11), tPA administration and application of LFTUS. Twenty-four hours after treatment, neurological change was evaluated, and brains were removed and examined histologically. RESULTS: There was no significant difference (p > 0.09) when comparing changes in neurologic status and body weight, infarct ratio, edema ratio, or hemorrhagic transformation among the four groups. CONCLUSIONS: Our findings suggest that sonothrombolytic treatment with LFTUS with appropriate parameters is safe when used for the treatment of ischemic stroke in hypertensiverats under the undesired permanent MCAO condition.