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  4. Identifying the Long-Term Role of Inducible Nitric Oxide Synthase after Contusive Spinal Cord Injury Using a Transgenic Mouse Model

Identifying the Long-Term Role of Inducible Nitric Oxide Synthase after Contusive Spinal Cord Injury Using a Transgenic Mouse Model

International Journal of Molecular Sciences, 2017 · DOI: 10.3390/ijms18020245 · Published: January 25, 2017

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

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.

Study Duration
6 Weeks
Participants
iNOS−/−knockout and wild-type (WT) control mice
Evidence Level
Not specified

Key Findings

  • 1
    iNOS−/− mice exhibited less preserved white and gray matter at six weeks post-SCI compared to wild-type controls.
  • 2
    iNOS−/− mice had fewer dorsal column axons and perilesional blood vessels rostral to the lesion than wild-type controls.
  • 3
    iNOS−/− mice showed an acute improvement in functional recovery after SCI within the first few weeks, but this improvement did not persist long-term.

Research Summary

This study examined the long-term effects of iNOS ablation in mice after spinal cord injury (SCI). The findings suggest that while acute iNOS inhibition may be beneficial, long-term ablation can be detrimental to tissue preservation and repair. The study highlights the complex role of iNOS in SCI and the importance of understanding the optimal duration of iNOS antagonism for therapeutic purposes.

Practical Implications

Therapeutic Timing

The optimal duration of iNOS inhibition is critical for maximizing benefits after SCI.

Angiogenesis and Repair

Long-term iNOS ablation may interfere with processes involved in injury resolution, angiogenesis, and endogenous recovery.

Further Research

Further studies are needed to understand the cell-specific roles of iNOS and NO in tissue remodeling and repair versus deleterious inflammatory processes.

Study Limitations

  • 1
    Restriction of histopathological tissue examination to the study’s endpoint at six weeks.
  • 2
    Use of female-only mice, which might have influenced axonal sparing.
  • 3
    The method of labeling the total number of neurofilament (NF)+ axons in this area provides a gross estimation of preserved dCST axons, as it does not differentiate between preserved and regenerating axons.

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