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

作者： Meghana Bhimreddy1, Denis Routkevitch1,2,3, Andrew M. Hersh1, Ali Mohammadabadi1,3, Arjun K. Menta1, Kelly Jiang1, Carly Weber-Levine1, A. Daniel Davidar1, Joshua Punnoose1,2,3, Kelley M. Kempski Leadingham1,3, Joshua C. Doloff2, Betty Tyler1, Nicholas Theodore1,3, Amir Manbachi1,2,3,4,5,6 1Department of Neurosurgery,Johns Hopkins University School of Medicine, 2Department of Biomedical Engineering,Johns Hopkins University, 3HEPIUS Innovation Laboratory,Johns Hopkins University School of Medicine, 4Department of Electrical Engineering and Computer Science,Johns Hopkins University, 5Department of Mechanical Engineering,Johns Hopkins University, 6Department of Anesthesiology and Critical Care Medicine,Johns Hopkins University

简介：

Overview

This protocol describes a method for transiently opening the blood-spinal cord barrier (BSCB) using microbubbles and low-intensity focused ultrasound (LIFU) in a rodent model. The technique allows for targeted delivery of therapies to the spinal cord, with confirmation of BSCB disruption through visual methods.

Key Study Components

Area of Science

• Neuroscience
• Biomedical Engineering
• Therapeutic Delivery Systems

Background

• The blood-spinal cord barrier is a critical structure with limited permeability.
• Opening the BSCB can enhance drug delivery for spinal cord treatments.
• This method utilizes ultrasound technology for precise localization.
• Visual confirmation of barrier disruption is achievable through microscopy.

Purpose of Study

• To develop a safe and effective method for BSCB disruption.
• To explore the potential for improved delivery of gene therapies and drugs.
• To assess the safety of the procedure in a rodent model.

Methods Used

• Intravenous administration of microbubbles.
• Application of low-intensity focused ultrasound (LIFU).
• Use of fluorescent microscopy for visualization of BSCB disruption.
• Histological analysis of spinal cord sections post-procedure.

Main Results

• Successful opening of the BSCB was confirmed via EBD extravasation.
• No neuronal damage or hemorrhage was observed in treated rats.
• Significantly greater EBD autofluorescence was noted in sonicated spinal cords.
• No changes in motor scores were detected post-sonication.

Conclusions

• The protocol effectively opens the BSCB without causing harm to spinal cord tissue.
• This method may enhance therapeutic delivery for spinal cord injuries.
• Further studies are warranted to explore clinical applications.

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