Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Hebei Medical University, Shijiazhuang, Hebei 050011, China.
Cereb Cortex. 2023 Nov 4;33(22):10984-10996. doi: 10.1093/cercor/bhad330.
Vascular remodeling is essential for patients with cerebral ischemic stroke (CIS). Our previous study proved that low-intensity pulsed ultrasound (LIPUS) could increase cortical hemodynamics. However, the effects and mechanisms of LIPUS on cerebral vascular remodeling after CIS are still unknown. In this study, we applied LIPUS to the mouse brain at 0.5 h after distal middle cerebral artery occlusion (dMCAO) and subsequently daily for a stimulation time of 30 min. Results showed that compared with the dMCAO group, LIPUS markedly increased cerebral blood flow (CBF), reduced brain swelling, and improved functional recovery at day 3 after CIS. LIPUS promoted leptomeningeal vasculature remodeling, enlarged vascular diameter, and increased the average vessel length and density at day 3 after CIS. Proteomic analysis highlighted that LIPUS mainly participated in the regulation of actin cytoskeleton pathway. Rho kinase 1 (ROCK1) was downregulated by LIPUS and participated in regulation of actin cytoskeleton. Subsequently, we verified that ROCK1 was mainly expressed in pericytes. Furthermore, we demonstrated that LIPUS inhibited ROCK1/p-MLC2 signaling pathway after CIS, which had positive effects on vascular remodeling and cerebral blood circulation. In conclusion, our preliminary study revealed the vascular remodeling effects and mechanism of LIPUS in CIS, provided evidence for potential clinical application of LIPUS.
血管重构对于脑缺血性中风（CIS）患者至关重要。我们之前的研究证明，低强度脉冲超声（LIPUS）可以增加皮质血流动力学。然而，LIPUS 对 CIS 后脑血管重构的影响和机制仍不清楚。在这项研究中，我们在大脑中动脉闭塞（dMCAO）后 0.5 h 时对小鼠的大脑应用 LIPUS，随后每天刺激 30 分钟。结果表明，与 dMCAO 组相比，LIPUS 可明显增加 CIS 后第 3 天的脑血流（CBF），减轻脑水肿，改善功能恢复。LIPUS 促进软脑膜血管重构，增加 CIS 后第 3 天的血管直径，并增加平均血管长度和密度。蛋白质组学分析突出表明，LIPUS 主要参与肌动蛋白细胞骨架途径的调节。Rho 激酶 1（ROCK1）被 LIPUS 下调并参与肌动蛋白细胞骨架的调节。随后，我们证实 ROCK1 主要表达在内皮细胞周围细胞中。此外，我们证明 LIPUS 在 CIS 后抑制 ROCK1/p-MLC2 信号通路，这对血管重构和脑血液循环有积极影响。总之，我们的初步研究揭示了 LIPUS 在 CIS 中的血管重构作用及其机制，为 LIPUS 的潜在临床应用提供了证据。
