title: Improved recovery after spinal cord injury in neuronal nitric oxide synthase-deficient mice but not in TNF-alpha-deficient mice.
abstract: Wild-type mice and mice lacking nitric oxide synthase (NOS) of neuronal type or TNF-alpha 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-alpha 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-alpha -/- 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.
authors.affiliation: Department of Genetics and Pathology, Uppsala University Hospital, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Farooque
authors.forename: J
authors.initials: J
authors.lastname: Isaksson
authors.forename: Y
authors.initials: Y
authors.lastname: Olsson
mesh_terms: D000818:Animals; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007211:Indoles; D051379:Mice; D018345:Mice, Knockout / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009069:Movement Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
chemical_list: D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D008869:Microtubule-Associated Proteins; D014409:Tumor Necrosis Factor-alpha; C018588:Luxol Fast Blue MBS; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase