International Journal of Molecular Sciences, 2017 · DOI: 10.3390/ijms18020245 · Published: January 25, 2017
This study investigates the long-term effects of iNOS ablation after spinal cord injury (SCI) using inos-null mice. Locomotor function was assessed weekly, and at the endpoint (six weeks), the volume of preserved white and gray matter, as well as the number of dorsal column axons and perilesional blood vessels rostral to the injury, were quantified. At weeks two and three after SCI, iNOS−/−mice exhibited a significant locomotor improvement compared to WT controls, although a sustained improvement was not observed during later weeks. At the endpoint, iNOS−/−mice showed significantly less preserved white and gray matter, as well as fewer dorsal column axons and perilesional blood vessels, compared to WT controls. While short-term antagonism of iNOS provides histological and functional benefits, its long-term ablation after SCI may be deleterious, blocking protective or reparative processes important for angiogenesis and tissue preservation.
The optimal duration of iNOS inhibition is critical for maximizing benefits after SCI.
Long-term iNOS ablation may interfere with processes involved in injury resolution, angiogenesis, and endogenous recovery.
Further studies are needed to understand the cell-specific roles of iNOS and NO in tissue remodeling and repair versus deleterious inflammatory processes.