Kaloss Alexandra M, Arnold Lauren N, Soliman Eman, Langman Maya, Groot Nathalie, Vlaisavljevich Eli, Theus Michelle H
Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA 24061, USA.
Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg VA 24061, USA.
BME Front. 2022 Jul 4;2022:9864910. doi: 10.34133/2022/9864910. eCollection 2022.
. This study examined the efficacy and safety of pulsed, low-intensity focused ultrasound (LIFU) and determined its ability to provide neuroprotection in a murine permanent middle cerebral artery occlusion (pMCAO) model. . Focused ultrasound (FUS) has emerged as a new therapeutic strategy for the treatment of ischemic stroke; however, its nonthrombolytic properties remain ill-defined. Therefore, we examined how LIFU influenced neuroprotection and vascular changes following stroke. Due to the critical role of leptomeningeal anastomoses or pial collateral vessels, in cerebral blood flow restoration and tissue protection following ischemic stroke, we also investigated their growth and remodeling. . Mice were exposed to transcranial LIFU (fundamental frequency: 1.1 MHz, sonication duration: 300 ms, interstimulus interval: 3 s, pulse repetition frequency: 1 kHz, duty cycle per pulse: 50%, and peak negative pressure: -2.0 MPa) for 30 minutes following induction of pMCAO and then evaluated for infarct volume, blood-brain barrier (BBB) disruption, and pial collateral remodeling at 24 hrs post-pMCAO. . We found significant neuroprotection in mice exposed to LIFU compared to mock treatment. These findings correlated with a reduced area of IgG deposition in the cerebral cortex, suggesting attenuation of BBB breakdown under LIFU conditions. We also observed increased diameter of CD31-postive microvessels in the ischemic cortex. We observed no significant difference in pial collateral vessel size between FUS and mock treatment at 24 hrs post-pMCAO. . Our data suggests that therapeutic use of LIFU may induce protection through microvascular remodeling that is not related to its thrombolytic activity.
本研究检测了脉冲式低强度聚焦超声（LIFU）的疗效和安全性，并确定了其在小鼠永久性大脑中动脉闭塞（pMCAO）模型中提供神经保护的能力。聚焦超声（FUS）已成为治疗缺血性中风的一种新的治疗策略；然而，其非溶栓特性仍不明确。因此，我们研究了LIFU如何影响中风后的神经保护和血管变化。由于软脑膜吻合支或软膜侧支血管在缺血性中风后脑血流恢复和组织保护中起关键作用，我们还研究了它们的生长和重塑。小鼠在pMCAO诱导后接受经颅LIFU（基频：1.1 MHz，超声持续时间：300 ms，刺激间隔：3 s，脉冲重复频率：1 kHz，每个脉冲的占空比：50%，峰值负压：-2.0 MPa）30分钟，然后在pMCAO后24小时评估梗死体积、血脑屏障（BBB）破坏和软膜侧支重塑情况。我们发现，与假处理相比，接受LIFU处理的小鼠有显著的神经保护作用。这些发现与大脑皮质中IgG沉积面积的减少相关，表明在LIFU条件下BBB破坏减轻。我们还观察到缺血皮质中CD31阳性微血管直径增加。在pMCAO后24小时，我们观察到FUS和假处理之间软膜侧支血管大小没有显著差异。我们的数据表明，LIFU的治疗应用可能通过与溶栓活性无关的微血管重塑诱导保护作用。
