Animal Study in Combining Targeted-microbubbles with Low-frequency Ultrasound for the Treatment of Ischemic Stroke

【Abstract】 Objective To study the treatment of ischemic stroke with combining targeted-microbubbles with low frequency ultrasound in animal model. Methods Cerebral thrombus animal model was established by the injection of autologous blood clots after cerebral angiogram through the carotid artery catheter in big white rabbit. With the confirm of thrombosis not being dissolved after angiography 6 h later, 49 big white rabbit were divided into four groups. Group A (n=13): direct injection of TMB through the vessel; group B (n=12): direct injection with nontargeted-microbubbles (NTMB) through the vessel; group C （n=12）：direct injection with tissue plasminogen activator (r-TPA) through the auricular vein; group D （n=12）： injection with saline through the vessel as control. Group A, B, D was given with transcutaneous temporal LFUS (1 MHz at 2.0 W/cm2) for 30 minutes. At 0 h, 1 h and 2 h after the treatments， imaging observation of thrombolytic and blood flow recanalization were performed. The venous blood was collected before and at 2 h after the treatment in embolization for the detection of prothrombin time (PT)， thrombin time (TT)，fibrinogen (Fib) and the d-dimer. Results Group A rabbit had six of 13 (46.15%) success thrombolysis， group B 12 rabbit had 1 of (8.33%) success thrombolysis，group C had 4 of 12 (33.33%) success thrombolysis，group D had 1 of 12 (8.33%) success thrombolysis. The thrombolytic rates of group A，C were higher than those of group B and D (P<0.01). After the treatments, the differences of PT, APTT，TT，Fib and the d-dimer in A，B and D group were not statistically significant, and d-dimer in group C was higher than that in other groups (P<0.05). Conclusion The treatment of combining targeted-microbubbles with low frequency ultrasound can rapidly release acute intracranial thrombotic occlusions, which has the same effect as r-TPA with less side effects.