Virginia Research Day 2022

Faculty Research Biomedical

04 Developing A Blast Spinal Cord Injury Model And Evaluating The Use Of A Neural Scaffold Treatment

Susan Murphy, PhD 2 ; Carly Norris, MS 2 ; Izabele Marquetti, PhD 1 ; Lana Maniakhina 1 ; Alan Boruch, DO, PhD 1 ; Pamela VandeVord, PhD 2 Corresponding author: murphysf@vt.edu

1VCOM Carolinas 2 Department of Biomedical Engineering & Mechanics, Virginia Tech

injections using the BBB Scale to assess the animals’ neurological and motor deficits. To demonstrate spinal cord injury, spines were harvested 24 and 72 hours post-blast/injections for IHC. ß-APP (label damaged axons) revealed no difference between the groups at each time point. However, there was an increased expression of β-APP at 72 hours post-blast compared to 24 hours post-blast suggesting axonal damage may be developing over time. GFAP (a marker for astrocytic activation when elevated) was significantly increased 72 hours post-blast (p<0.05) both the blast and blast + injection cords compared to sham and sham + injection. Glial activation appears to increase over 72 hours throughout the cords, indicating diffuse injury. Neurofilament light (NF-L) (to reflect axonal damage) revealed no statistical difference between the groups at each time point. However, comparing 24 hours to 72 hours post-blast there is an apparent initial increase in NF-L (not significant) that returns to the same level as sham animals by 72 hours.

the blast injury to the spine and minimize injuries to vital organs. A single blast exposure was employed where the magnitude of blast overpressure (BOP) was measured between 20 – 27 psi. However, the addition of the fixture introduces reflections, thus amplifying the magnitudes measured by the wall sensors. For a more accurate measure of the pressure experienced by the specimen at the injury site, the fixture was instrumented with a piezoelectric pressure sensor (PCB Piezotronics, 102B16). Each animal was exposed to a single blast wave where the reflective pressures measured at the location of the spinal cord in the bSCI fixture ranged from 67.55 – 79.05 psi. Injection procedure: Immediately after blast/ sham, while still under anesthesia the neural scaffold treatment (2 μl) was injected in the T13-L1 space at the rate of 0.3 μl per minute using a microinfusion pump; thus, a minimally invasive approach without laminectomy was used. There were 4 groups: Sham, Sham + injection, Blast, Blast + injection. Rats were monitored daily up to 72 hours post-blast/

This initial phase of research was to develop a blast spinal cord injury (bSCI) model and optimize a minimally invasive spinal cord injection. In addition, in this pilot study, we assess a novel injectable biologic neural scaffold including its short-term effects on spinal cord tissue damage and recovery of function when injected into the injury site immediately after blast trauma. The broad, long-term goals of this study are to 1) develop a bSCI model that closely re-creates the clinical scenario faced by military personnel, and 2) characterize a novel injectable neural scaffold and evaluate its short-term effects on tissue damage and functional recovery after blast-induced spinal cord injury. The data generated will be used to develop clinically relevant treatment paradigms that can be used immediately after spinal cord injury. A custom- designed bSCI fixture was built to support the anesthetized animal on its side inside the ABS with its spine facing the oncoming shock front and concentrating the blast wave on the spine. The bSCI fixture was designed to isolate

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