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

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

J Vis Exp, 2024 · DOI: 10.3791/65113 · Published: April 2, 2024

PharmacologyNeurologyBiomedical

Simple Explanation

This study introduces a method for disrupting the blood-spinal cord barrier (BSCB) in rats using low-intensity focused ultrasound (LIFU). The technique involves using ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. The method involves administering microbubbles (MBs) intravenously, followed by LIFU sonication to create transient gaps in the capillaries of the spinal cord, allowing substances like drugs to penetrate into the spinal parenchyma. The confirmation of BSCB disruption is visually evaluated by observing the extravasation of Evans blue dye (EBD) into the spinal cord, identifiable by its rich blue color.

Study Duration
5 days
Participants
Adult Sprague-Dawley female rats (average weight: 250 g; age: 11 weeks)
Evidence Level
Not specified

Key Findings

  • 1
    The concurrent application of LIFU sonication and MB administration is an effective technique for localized BSCB disruption, indicated by the presence of EBD extravasation into the spinal parenchyma.
  • 2
    All rats that received MB administration and LIFU sonication show apparent extravasation of EBD into the spinal cord, while negative controls that received MBs and EBD with no LIFU sonication do not.
  • 3
    H&E analysis revealed no neuronal damage, hemorrhage, or cavity lesions present in the sonicated locations, supporting the safety of this procedure.

Research Summary

This protocol describes a method for disrupting the blood-spinal cord barrier (BSCB) in rats using low-intensity focused ultrasound (LIFU) and microbubbles (MBs). The technique involves animal preparation, LIFU equipment setup, MB administration, target localization, and spinal cord extraction, with confirmation of BSCB disruption via Evans blue dye extravasation. The study emphasizes the advantages of this method, including quick real-time visual confirmation of BSCB disruption and ease of targeting, making it a useful tool for researchers to test LIFU transducer targeting capabilities.

Practical Implications

Drug Delivery Enhancement

BSCB disruption can improve the delivery of therapeutics to the spinal cord, potentially enhancing the treatment of spinal cord injuries and other related conditions.

Immunomodulation Therapies

LIFU-mediated BSCB disruption can be used to modulate immune responses in the spinal cord, offering new avenues for treating autoimmune and inflammatory disorders.

Neuromodulation Applications

This technique can facilitate neuromodulation in specific regions of the spinal cord, providing a non-invasive method for managing chronic pain and other neurological conditions.

Study Limitations

  • 1
    This study represents a single center experience for LIFU-mediated BSCB disruption.
  • 2
    This protocol does not test or optimize various sonication energy parameters and MB concentrations.
  • 3
    Another limitation of this procedure is the invasive nature of the laminectomy.

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