Effectiveness of Low-Intensity Focused Ultrasound in Improving Drug Delivery to the Chronic Spinal Cord Injury by Disrupting the Blood-Spinal Cord Barrier
Post-Doctoral Neurosurgery Research Fellow Johns Hopkins University Baltimore, MD, US
Introduction: Chronic spinal cord injury (cSCI) is challenging due to long-term disabilities from blood-spinal cord barrier (BSCB) reformation and glial scarring, which hinder natural and therapeutic regeneration. Low-intensity focused ultrasound (LIFU) offers a promising solution by temporarily disrupting the BSCB to improve the delivery of therapies like umbilical cord-derived mesenchymal stem cells (UCMSCs). Advanced imaging techniques, including super-resolution ultrasound localization microscopy (ULM), enable detailed visualization of vascular changes following injury, aiding in optimizing treatment strategies.
Methods: Female Sprague-Dawley rats with contusion-induced cSCI underwent LIFU application for BSCB disruption, monitored via ultrasound. ULM analyzed hemodynamic changes (vascular density and flow speed) in injury-adjacent regions. UCMSCs were administered intravenously, and functional recovery was tracked through Basso, Beattie, and Bresnahan (BBB) scores over six weeks. Histopathology and immunohistochemistry (GFAP and MBP) assessed astrocyte activation and remyelination.
Results: LIFU-treated rats showed a marked increase in BSCB permeability, with Evans Blue (EB) concentration significantly higher at the injury site (0.237 μg/g, SD = 0.035) in the LIFU+ group compared to controls (0.08 μg/g, SD = 0.04, p < 0.01). Vascular density (VD) dropped from 1.74 in controls to 0.36 acutely, later recovering to 1.16 in the chronic phase (p < 0.001), and flow speed followed a similar trend (p < 0.05).
For functional recovery, BBB scores in the LIFU/IV-UCMSC group improved significantly by day 40 (11.2 ± 1.79) compared to the IV-UCMSC (9.0 ± 0.01) and IV-NSS (9.5 ± 0.84) groups (p < 0.05). Cavity size at the injury epicenter was reduced in the LIFU/IV-UCMSC group (6.83% ± 0.77) relative to IV-UCMSC alone (10.5% ± 1.75, p = 0.012). Immunohistochemistry revealed reduced GFAP % area (3.8% ± 0.2 in LIFU/IV-UCMSC) compared to controls and higher myelinated axon counts (66 ± 5.57) in treated rats (p < 0.05), indicating enhanced remyelination and astrocyte suppression, supporting LIFU's therapeutic potential in cSCI.
Conclusion : LIFU shows promise in enhancing cSCI treatment by improving cellular infiltration, reducing inflammation, and promoting tissue repair. These findings support LIFU’s potential integration into clinical protocols to optimize drug delivery and accelerate functional recovery, marking a pivotal step in personalized therapies for cSCI.