Improved Recovery After Spinal Cord Injury in Neuronal Nitric Oxide Synthase-Deficient Mice But not in TNF-α-Deficient Mice

Abstract

Wild-type mice and mice lacking nitric oxide synthase (NOS) of neuronal type or TNF-α were subjected to an extradural compression of the thoracic spinal cord. The functional outcome of the hind limbs was assessed by using a motor function score (MFS). The injury resulted in paraplegia of the hind limbs in wild-type mice at day 1 after injury. Gradual recovery was observed during the following 14 days. Injured NOS -/- animals had an improved hind limb motor function during the entire observation period compared to wild-type controls. The difference was statistically significant on day 10 (p < 0.022) and day 14 (p < 0.048) after injury. At the site of injury, there was a trend of gray matter preservation in NOS -/- mice, as measured by MAP2 staining (p < 0.077). Injured mice lacking TNF-α had the lowest motor score among all the groups on day 1. During the following period, they had motor scores similar to those of wild-type controls and there was no significant difference at any time point. TNF-α -/- animals showed a trend of decreased white matter preservation compared to wild-type animals (p < 0.097). Our study shows that after spinal cord injury, mice lacking NOS have a better functional ability of their hind limbs than controls with the same degree of injury. This would indicate that the functional outcome is influenced in a negative way in wild mice by the presence of NO. The degree of secondary damage to the spinal cord might be attenuated in NOS-deficient mice.