Ho Yi-Ju, Cheng Hsiang-Lung, Liao Lun-De, Lin Yu-Chun, Tsai Hong-Chieh, Yeh Chih-Kuang
Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Biomater Res. 2023 Jul 6;27(1):65. doi: 10.1186/s40824-023-00400-y.
Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R.
The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function.
The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.
缺血性脑卒中再灌注（S/R）损伤是溶栓后脑功能保护中的关键问题。超声（US）刺激微泡空化诱导的血管舒张已被应用于通过超声灌注减少S/R损伤。本研究使用载氧微泡（OMB）并结合US刺激来提供超声灌注和局部氧疗，以减少S/R后脑梗死体积并实现神经保护。
通过光动力血栓形成和在前脑动脉远端分支进行溶栓建立小鼠S/R模型。检测体内血流、局部氧分压（pO）和脑梗死染色，以分析动物模型的有效性和OMB治疗效果。利用动物行为和脑梗死面积测量来评估脑功能的长期恢复情况。
中风60分钟、再灌注20分钟和OMB治疗10分钟后，血流百分比分别为45±3%、70±3%和86±2%，表明存在超声灌注，相应的pO水平分别为60±1%、76±2%和79±4%，显示出再氧合。治疗14天后，S/R小鼠的脑梗死面积减少了87±3%，肢体协调性恢复。NF-κB、HIF-1α、IL-1β和MMP-9的表达受到抑制，而eNOS、BDNF、Bcl2和IL-10的表达增强，表明抗炎和抗凋亡反应激活以及神经保护作用。我们的研究表明，OMB治疗结合了超声灌注和局部氧疗的有益效果，可减少脑梗死并激活神经保护作用以预防S/R损伤。
