Early nanoparticle intervention preserves motor function following cervical spinal cord injury

Abstract

Spinal cord injury (SCI) triggers an immediate influx of immune cells that secrete pro‐inflammatory cytokines and reactive oxygen species that cause tissue damage that is secondary to the initial physical trauma. We aim to reprogram these immune cells to promote a less inflammatory and more pro‐regenerative environment. Herein, we investigated the window in time during which poly(lactide‐co‐glycolide) nanoparticles (NPs) administration can successfully modulate the immune response and promote functional sparing. The dynamics of immune cell infiltration and secondary tissue damage were studied following the injection of NPs intravenously every 24 h for 7 days following injury, with the first injection starting at 2, 4, or 24 hours post‐injury (hpi). At 7 days post‐injury (dpi), early NP intervention decreased the number of infiltrating macrophages and neutrophils, but delaying treatment until 24 hpi increased the number of neutrophils above control. All mice that received NPs had greater neuronal sparing contralateral to the injury, but mice that received NPs at early timepoints had greater neuromuscular junction innervation and motor endplate sparing. The increased sparing of neurons and neural circuits in the 2 hpi NP group corresponded with increased motor function, as measured by a ladder beam test. Collectively, these results suggest that early intervention with NPs can modulate the inflammatory response and preserve motor function and circuits following SCI.