斯坦福大学医学院Raag D. Airan小组近日取得一项新成果。经过不懈努力，他们探明了超声清除颅内碎屑可减轻炎症并改善出血性卒中模型的预后。相关论文于2025年11月10日发表在《自然—生物技术》杂志上。

在这里，该团队报告了一种低强度，聚焦超声方案，无创清除小鼠脑脊液和脑间质中的致病性物质。使用两种出血性中风模型，该研究组证明该方案清除脑脊液和间质的血细胞，这些血细胞通过脑膜淋巴管积聚在颈深部淋巴结。该方案直接调节分子过程，包括机械敏感通道，以改变小胶质细胞表型和星形细胞水通道蛋白定位，以减少神经炎症和神经细胞毒性。在脑出血模型中，它改善了行为结果，提高了生存率，比药理学基准更有效。该方案符合美国食品和药物管理局的安全指南，支持临床可翻译性。如果临床证明有效，它不仅可以治疗出血性中风，还可以治疗其他涉及碎片清除受损的神经系统疾病。

据悉，大脑中神经毒性碎片的清除受损加剧了神经系统疾病，并提出了一个有希望的治疗靶点。在临床前模型中，药物治疗可以增强脑膜淋巴清除，但可能受到全身毒性或侵入性给药的限制。

附：英文原文

Title: Clearance of intracranial debris by ultrasound reduces inflammation and improves outcomes in hemorrhagic stroke models

Author: Azadian, Matine M., Kiani Shabestari, Sepideh, Rajan, Arjun, Martinez, Payton J., Macedo, Nicholas, Markarian, Eric, Xiang, Yun, Yu, Brenda J., George, Paul M., Fame, Ryann M., Airan, Raag D.

Issue&Volume: 2025-11-10

Abstract: Impaired clearance of neurotoxic debris in the brain exacerbates neurologic disease and presents a promising therapeutic target. Pharmacologic therapies can enhance meningeal lymphatic clearance in preclinical models but may be limited by systemic toxicities or invasive administration. Here we report a low-intensity, focused ultrasound protocol that noninvasively clears pathogenic substances from the cerebrospinal fluid and brain interstitium in mice. Using two models of hemorrhagic stroke, we demonstrate that this protocol clears the cerebrospinal fluid and interstitium of blood cells, which accumulate in the deep cervical lymph nodes via meningeal lymphatics. The protocol directly modulates molecular processes, including mechanosensitive channels, to shift microglial phenotypes and astrocytic aquaporin localization to reduce neuroinflammation and neurocytotoxicity. In the intracerebral hemorrhage model, it improves behavioral outcomes and increases survival with greater efficacy than a pharmacologic benchmark. The protocol satisfies Food and Drug Administration safety guidelines, supporting clinical translatability. If demonstrated effective clinically, it may provide therapeutic benefit not only in hemorrhagic stroke but also in other neurologic disorders that involve impaired debris clearance.

DOI: 10.1038/s41587-025-02866-8

Source: https://www.nature.com/articles/s41587-025-02866-8