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利用低强度聚焦超声破坏血脊髓屏障的大鼠模型。

Disruption of the Blood-Spinal Cord Barrier using Low-Intensity Focused Ultrasound in a Rat Model.

机构信息

Department of Neurosurgery, Johns Hopkins University School of Medicine.

Department of Neurosurgery, Johns Hopkins University School of Medicine; Department of Biomedical Engineering, Johns Hopkins University; HEPIUS Innovation Laboratory, Johns Hopkins University School of Medicine.

出版信息

J Vis Exp. 2023 Mar 10(193). doi: 10.3791/65113.

Abstract

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. Although LIFU-mediated blood-brain barrier (BBB) opening has been explored in detail, no standardized technique for blood-spinal cord barrier (BSCB) opening has been established to date. Therefore, this protocol presents a method for successful BSCB disruption using LIFU sonication in a rat model, including descriptions of animal preparation, microbubble administration, target selection and localization, as well as BSCB disruption visualization and confirmation. The approach reported here is particularly useful for researchers who need a fast and cost-effective method to test and confirm target localization and precise BSCB disruption in a small animal model with a focused ultrasound transducer, evaluate the BSCB efficacy of sonication parameters, or explore applications for LIFU at the spinal cord, such as drug delivery, immunomodulation, and neuromodulation. Optimizing this protocol for individual use is recommended, especially for advancing future preclinical, clinical, and translational work.

摘要

低强度聚焦超声(LIFU)使用的超声脉冲强度低于超声,目前正在被测试作为一种可逆且精确的神经调节技术。尽管已经详细探索了 LIFU 介导的血脑屏障(BBB)开放,但迄今为止尚未建立用于血脊髓屏障(BSCB)开放的标准化技术。因此,本方案提出了一种使用 LIFU 超声在大鼠模型中成功破坏 BSCB 的方法,包括动物准备、微泡给药、目标选择和定位以及 BSCB 破坏可视化和确认的描述。这里报道的方法特别适用于需要快速、经济有效的方法来测试和确认小动物模型中聚焦超声换能器的目标定位和精确 BSCB 破坏的研究人员,评估超声参数对 BSCB 的有效性,或探索 LIFU 在脊髓中的应用,如药物输送、免疫调节和神经调节。建议针对个人使用优化此方案,特别是在推进未来的临床前、临床和转化工作方面。

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Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies.
NeuroSci. 2021 Dec 21;3(1):1-27. doi: 10.3390/neurosci3010001. eCollection 2022 Mar.
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Opening of the Blood-Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models.
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Focused Ultrasound-Induced Blood-Spinal Cord Barrier Opening Using Short-Burst Phase-Keying Exposures in Rats: A Parameter Study.
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