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使用低强度聚焦超声恢复光血栓性中风后的淋巴系统流入

Restoration of Glymphatic Influx After Photothrombotic Stroke Using Low-Intensity Focused Ultrasound.

作者信息

Hsiao Ming-Yen, Lin Yu-Ling, Lin Meng-Ting, Liao Wei-Hao, Chen Wen-Shiang, Wu Chueh-Hung

机构信息

Department of Physical Medicine and Rehabilitation, College of Medicine, National Taiwan University, Taipei, Taiwan.

Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

CNS Neurosci Ther. 2025 Jun;31(6):e70451. doi: 10.1111/cns.70451.

DOI:10.1111/cns.70451
PMID:40457518
Abstract

AIMS

This study aimed to investigate the regional modulation effect of low-intensity focused ultrasound (LIFU) on cerebrospinal fluid (CSF) influx dynamics, focusing on the differential changes between hemispheres in a mouse model of unilateral ischemic stroke.

METHODS

LIFU was administered with a commercial transducer at the unilateral M1 cortex of mice using specific parameters (0.5 MHz center frequency, 250 kHz pulse repetition frequency, 300 ms burst duration, 2 ms pulse length, 50% intraburst duty factor, 2 s interstimulation interval, spatial peak temporal average intensities of 0.5 W/cm, and a total sonication duration of 10 min). The regional CSF influx was observed through in vivo macroscopy and brain section imaging in a photothrombotic stroke model, both with and without LIFU.

RESULTS

Localized LIFU stimulation at the M1 region triggered a rapid CSF influx, peaking 20-30 min poststimulation. Following photothrombotic stroke, a marked reduction in CSF influx was observed in both ipsilesional and contralesional MCA regions, most notably on Days 1 and 3, with a return to baseline by Day 7. However, daily contralesional LIFU stimulation for 7 days effectively restored CSF influx on both sides.

CONCLUSION

Daily contralesional LIFU stimulation restores impaired CSF influx bilaterally after stroke, suggesting potential therapeutic implications for stroke-related pathophysiology.

摘要

目的

本研究旨在探讨低强度聚焦超声(LIFU)对脑脊液(CSF)流入动力学的区域调节作用,重点关注单侧缺血性中风小鼠模型中半球间的差异变化。

方法

使用商用换能器,以特定参数(中心频率0.5 MHz、脉冲重复频率250 kHz、脉冲串持续时间300 ms、脉冲长度2 ms、脉冲串内占空比50%、刺激间隔2 s、空间峰值时间平均强度0.5 W/cm以及总超声处理持续时间10 min)对小鼠单侧M1皮质进行LIFU治疗。在光血栓性中风模型中,通过体内宏观成像和脑切片成像观察有无LIFU时的区域脑脊液流入情况。

结果

M1区域的局部LIFU刺激引发脑脊液快速流入,在刺激后20 - 30分钟达到峰值。光血栓性中风后,同侧和对侧大脑中动脉区域的脑脊液流入均显著减少,最明显的是在第1天和第3天,到第7天恢复至基线水平。然而,连续7天对侧LIFU刺激可有效恢复双侧脑脊液流入。

结论

中风后连续7天对侧LIFU刺激可双侧恢复受损的脑脊液流入,提示其对中风相关病理生理学具有潜在治疗意义。

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本文引用的文献

1
In vivo two-photon microscopy imaging of focused ultrasound-mediated glymphatic transport in the mouse brain.聚焦超声介导的小鼠脑内类淋巴系统转运的体内双光子显微镜成像
J Cereb Blood Flow Metab. 2025 Feb 22:271678X251323369. doi: 10.1177/0271678X251323369.
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Very Low-Intensity Ultrasound Facilitates Glymphatic Influx and Clearance via Modulation of the TRPV4-AQP4 Pathway.极低强度超声通过调节TRPV4-AQP4通路促进淋巴系统内流和清除。
Adv Sci (Weinh). 2024 Dec;11(47):e2401039. doi: 10.1002/advs.202401039. Epub 2024 Nov 4.
3
Transcranial focused ultrasound stimulation enhances cerebrospinal fluid movement: Real-time in vivo two-photon and widefield imaging evidence.
经颅聚焦超声刺激增强脑脊液流动:实时在体双光子和宽场成像证据。
Brain Stimul. 2024 Sep-Oct;17(5):1119-1130. doi: 10.1016/j.brs.2024.09.006. Epub 2024 Sep 12.
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Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke.类淋巴系统损伤促进缺血性脑卒中后脑水肿的形成。
Stroke. 2024 May;55(5):1393-1404. doi: 10.1161/STROKEAHA.123.045941. Epub 2024 Mar 27.
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Non-invasive enhancement of intracortical solute clearance using transcranial focused ultrasound.经颅聚焦超声无创增强脑皮质内溶质清除。
Sci Rep. 2023 Jul 31;13(1):12339. doi: 10.1038/s41598-023-39640-2.
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Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles.通过超声联合微泡机械操纵脑淋巴系统转运。
Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2212933120. doi: 10.1073/pnas.2212933120. Epub 2023 May 15.
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Movement of cerebrospinal fluid tracer into brain parenchyma and outflow to nasal mucosa is reduced at 24 h but not 2 weeks post-stroke in mice.脑脊髓液示踪剂向脑组织的移动和向鼻腔黏膜的流出在中风后 24 小时减少,但在 2 周后不减少。
Fluids Barriers CNS. 2023 Apr 11;20(1):27. doi: 10.1186/s12987-023-00427-2.
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Sci Rep. 2022 Jul 28;12(1):12940. doi: 10.1038/s41598-022-17314-9.
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Clin Neurophysiol. 2022 Mar;135:51-73. doi: 10.1016/j.clinph.2021.12.010. Epub 2021 Dec 31.