Ultrasound-Induced Blood-Spinal Cord Barrier Opening in Rabbits

Anne-Sophie Montero; Franck Bielle; Lauriane Goldwirt; Adrien Lalot; Guillaume Bouchoux; Michael Canney; Florine Belin; Kevin Beccaria; Pierre-François Pradat; François Salachas; Severine Boillée; Christian Lobsiger; Cyril Lafon; Jean-Yves Chapelon; Alexandre Carpentier

doi:10.1016/j.ultrasmedbio.2019.05.022

Ultrasound-Induced Blood-Spinal Cord Barrier Opening in Rabbits

Ultrasound Med Biol. 2019 Sep;45(9):2417-2426. doi: 10.1016/j.ultrasmedbio.2019.05.022. Epub 2019 Jun 24.

Authors

Affiliations

¹ Sorbonne Universite, Neurosurgery Department, AP-HP, Hopital de la Pitie Salpêtrière, Paris, France; Advanced Surgical Research Technology Laboratory, Sorbonne Universite, Paris, France.
² Sorbonne Universite, Department of Neuropathology, AP-HP, Hopital de la Pitie Salpêtrière, Paris, France.
³ Pharmacology Department, AP-HP, Hopital de Saint-Louis, Paris, France.
⁴ Université Paris Descartes, Laboratoire de Recherches Biochirurgicales, Hôpital Européen Georges Pompidou, Paris, France.
⁵ Advanced Surgical Research Technology Laboratory, Sorbonne Universite, Paris, France.
⁶ Sorbonne Universite, Endocrinology Department, AP-HP, Hopital de la Pitie Salpêtrière, Paris, France.
⁷ Advanced Surgical Research Technology Laboratory, Sorbonne Universite, Paris, France; Universite Paris Descartes, Department of Pediatric Neurosurgery, AP-HP, Hopital Necker, Paris, France.
⁸ Centre de Reference Maladie Rare SLA, Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France; Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France; Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute Ulster University, C-TRIC, Altnagelvin Hospital, Derry/Londonderry, United Kingdom.
⁹ Centre de Reference Maladie Rare SLA, Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France.
¹⁰ Inserm U 1127, CNRS UMR 7225, Sorbonne Université, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
¹¹ LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Lyon, France.
¹² Sorbonne Universite, Neurosurgery Department, AP-HP, Hopital de la Pitie Salpêtrière, Paris, France; LabTAU, INSERM, Centre Léon Bérard, Université Lyon 1, Lyon, France. Electronic address: [email protected].

PMID: 31248640
DOI: 10.1016/j.ultrasmedbio.2019.05.022

Abstract

The blood-spinal cord barrier (BSCB) considerably limits the delivery and efficacy of treatments for spinal cord diseases. The blood-brain barrier can be safely opened with low-intensity pulsed ultrasound when microbubbles are simultaneously administered intravenously. This technique was tested on the BSCB in a rabbit model in this work. Twenty-three segments of spinal cord were sonicated with a 1-MHz unfocused pulsed ultrasound device and compared with non-sonicated segments. BSCB disruption was assessed using Evan's blue dye (EBD) extravasation. Tolerance was assessed by histologic analysis. An increased EBD concentration indicating BSCB disruption was clearly observed in sonicated segments compared with controls (p = 0.004). On one animal, which received 10 sonications, repetitive BSCB disruptions revealed no evidence of cumulative toxicity. BSCB can be disrupted using an unfocused pulsed ultrasound device in combination with microbubbles without neurotoxicity even in case of repeated sonications.

Keywords: Blood–brain barrier; Blood–spinal cord barrier; Drug delivery; Spinal cord; Ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Contrast Media / pharmacokinetics
Evans Blue / pharmacokinetics
Microbubbles
Models, Animal
Phospholipids / pharmacokinetics
Rabbits
Spinal Cord / metabolism*
Sulfur Hexafluoride / pharmacokinetics
Ultrasonics / methods*

Substances

Contrast Media
Phospholipids
contrast agent BR1
Evans Blue
Sulfur Hexafluoride