Glucocorticoids, given at high-doses, improve recovery of function after
spinal cord injury (SCI) in animals. However, side effects combined with a limited efficacy in clinical trials have restricted their usefulness for treatment of SCI patients. Recent studies have shown that incorporation of the
nitric oxide releasing moiety into the
glucocorticoid structure enhances anti-inflammatory properties and reduces side effects. One compound, a derivative of
prednisolone (PRE), (
NCX 1015,
prednisolone 21 [(4'nitrooxymethyl)
benzoate]), has interesting pharmacological properties. Therefore, we investigated its effects on apoptosis and recovery of function in rats after SCI. Rats received subcutaneously vehicle,
NCX 1015 or PRE (37 micromol/kg, each) 3.5 h after a standardized thoracic lesion. The treatment was continued once a day for 3 days and the effect of both
steroids on apoptosis was examined by immunohistochemistry 24 h after the last injection.
NCX 1015 but not PRE reduced TUNEL and activated
caspase 3 in both white and ventral gray matter as well as
tumor necrosis factor immunoreactivity in ventral horn motorneurons, suggesting that
NCX 1015 reduces SCI-induced apoptosis. The effect of
NCX 1015 on motor function was then examined by a standard locomotion rating scale (BBB) starting at 1 day after injury and continuing up to 14 days.
NCX 1015 improved significantly locomotor activity by 4 days after injury, whereas PRE had an effect equivalent to that of vehicle, thus providing a correlation between the antiapoptotic effect of
NCX1015 and its ability to improve recovery of function. The data suggest that
NCX 1015 might be a novel experimental therapeutic compound for recovery of function in SCI patients.