Objectives/Goals: Previous studies of nanoparticles in a penetrating spinal cord injury demonstrated their ability to modulate immune responses to reduce secondary injury. This study investigated nanoparticles in contusion injury models, which is more common clinically, to quantify their efficacy as a function of injury severity. Methods/Study Population: Female C57BlJ/6 mice were anesthetized, and a T9/T10 laminectomy was performed to expose the spinal cord. A stereotactic setup with an Infinite Horizon impactor was used to position the spinal cord to receive a mild (30 kdyne), moderate (50 kdyne), or severe (70 kdyne) contusive injury. Within two hours of injury, poly(lactide-co-glycolide) nanoparticles, formed via a single emulsion with sonication protocol, or phosphate-buffered saline (PBS) vehicle were injected intravenously via tail vein injection. Nanoparticles (NPs) or PBS were administered daily for 7 days. Function was evaluated using the Basso Mouse Scale (BMS) test for hind limb function starting 3 days post-injury and repeated weekly thereafter, as well as a horizontal ladder beam test once they had recovered to at least occasional plantar stepping. Results/Anticipated Results: In the moderate injury group, NP-treated mice had significantly higher BMS scores starting 6 weeks post-injury (p=0.009), with the NP-treated mice performing better than control to the end of the study. In the mild injury group, NP-treated mice scored significantly better on BMS starting at 3 days post-injury (p=0.005). This difference persisted through week 4, and then the vehicle-treated mice maintained a slightly lower score through the end of the study. In the severe injury group, no significant difference on BMS scores was observed between groups and animals did not recover enough function to be evaluated via ladder beam. Scoring of the ladder beam test for moderate and mild injury studies is underway. Animals treated with NPs are anticipated to have a significantly higher number of successful steps compared to control. Discussion/Significance of Impact: Spinal cord injury consists of a primary injury and secondary injury caused by inflammation at the injury site. Nanoparticles present an opportunity to reduce secondary injury to improve functional outcomes of individuals with SCI. This study of NPs in a graded severity contusion model further illustrates the feasibility and utility of NPs in SCI.
Schwartz et al. (Wed,) studied this question.