Saguchi Takayuki, Onoue Hisashi, Urashima Mitsuyoshi, Ishibashi Toshihiro, Abe Toshiaki, Furuhata Hiroshi
Department of Neurosurgery, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Stroke. 2008 Mar;39(3):1007-11. doi: 10.1161/STROKEAHA.107.496117. Epub 2008 Jan 31.
Transcranial ultrasound (TUS) enhances thrombolysis and is expected to be useful for the treatment of ischemic stroke. However, neither its effectiveness in improving neurologic outcome nor its safety in living tissue has been fully established. We examined the efficacy and safety of low-frequency TUS under appropriate conditions of ultrasound for thrombolytic treatment in a rat middle cerebral artery stroke model.
Sixty-five male Wistar rats were used. Rats with right middle cerebral artery stroke exhibiting left hemiparesis were blindly selected and randomly assigned to 1 of 3 groups: (1) control, no therapy; (2) tPA, intravenous administration of tissue plasminogen activator 3 hours after middle cerebral artery stroke, or (3) TUS, tPA administration and application of TUS (490 kHz, continuous wave, at an intensity of 0.8 W/cm(2)). Twenty-four hours after the onset of stroke, neurologic improvement was evaluated and brains were then removed. Thrombolysis at the origin of the right middle cerebral artery was examined. Thrombolysis ratio, cerebral infarct ratio, and rate of histologic evidence of hemorrhage were compared in the 3 groups.
Significantly better neurologic improvement (P=0.008), a higher thrombolysis ratio (P=0.041), and a reduction of cerebral infarct volume (P=0.047) were obtained in the TUS group compared with the tPA group, without an increase in hemorrhagic transformation.
Our findings suggest that thrombolytic treatment with low-frequency TUS under appropriate conditions could be an effective and safe method of treatment for ischemic stroke.
经颅超声（TUS）可增强溶栓效果，有望用于缺血性脑卒中的治疗。然而，其在改善神经功能结局方面的有效性及其在活体组织中的安全性均未得到充分证实。我们在大鼠大脑中动脉卒中模型中，研究了在适当超声条件下低频TUS溶栓治疗的有效性和安全性。
使用65只雄性Wistar大鼠。将出现左侧偏瘫的右侧大脑中动脉卒中大鼠随机分为3组：（1）对照组，不进行治疗；（2）tPA组，大脑中动脉卒中后3小时静脉注射组织型纤溶酶原激活剂；（3）TUS组，注射tPA并应用TUS（490kHz，连续波，强度为0.8W/cm²）。卒中发作24小时后，评估神经功能改善情况，然后取出大脑。检查右侧大脑中动脉起始处的溶栓情况。比较3组的溶栓率、脑梗死率和组织学出血证据发生率。
与tPA组相比，TUS组神经功能改善明显更好（P=0.008），溶栓率更高（P=0.041），脑梗死体积减小（P=0.047），且出血性转化未增加。
我们的研究结果表明，在适当条件下用低频TUS进行溶栓治疗可能是一种有效且安全的缺血性脑卒中治疗方法。
