Catalytic antioxidant nanoparticles mitigate secondary injury progression and promote functional recovery in spinal cord injury model

Abstract

Traumatic spinal cord injury exacerbates disability with time due to secondary injury cascade triggered largely by overproduction of reactive oxygen species (ROS) at the lesion site, causing oxidative stress. This study explored nanoparticles containing antioxidant enzymes (antioxidant NPs) to neutralize excess ROS at the lesion site and its impact. When tested in a rat contusion model of spinal cord injury, a single dose of antioxidant NPs, administered intravenously three hours after injury, effectively restored the redox balance at the lesion site, interrupting the secondary injury progression. This led to reduced spinal cord tissue inflammation, apoptosis, cavitation, and inhibition of syringomyelia. Moreover, the treatment reduced scar tissue forming collagen at the lesion site, protected axons from demyelination, and stimulated lesion healing, with further analysis indicating the formation of immature neurons. The ultimate effect of the treatment was improved motor and sensory functions and rapid post-injury weight loss recovery. Histological analysis revealed activated microglia in the spinal cord displaying rod-shaped anti-inflammatory and regenerative phenotype in treated animals, contrasting with amoeboid inflammatory and degenerative phenotype in untreated control. Overall data suggest that restoring redox balance at the lesion site shifts the dynamics in the injured spinal cord microenvironment from degenerative to regenerative, potentially by promoting endogenous repair mechanisms. Antioxidant NPs show promise to be developed as an early therapeutic intervention in stabilizing injured spinal cord for enhanced recovery.

Keywords: Biodegradable polymer; Drug delivery; Free radicals; Neurodegeneration; Oxidative stress.