Therapeutic time window for methylprednisolone in spinal cord injured rat

Recent clinical trials have reported that methylprednisolone sodium succina te administered within 8 hours improves neurological recovery in human spin al cord injury (SCI). Methylprednisolone, however, was ineffective and poss ibly even deleterious when given more than 8 hours after injury. This findi ng suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone t reatment for optimal neuroprotection, a single or two bolus dose of methylp rednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. af ter three graded spinal cord injury. The primary outcome measure was 24-hou r spinal cord lesion volumes estimated from spinal cord Na+ and K+ shifts. A single 30 mg/kg dose of methylprednisolone at 10 min, after injury signif icantly reduced 24-hour lesion volumes in injured rat spinal cords. However , any other methylprednisolone treatment starting 30 min, or more after inj ury had no effect on 24-hour lesion volumes compared to the vehicle control group. Moreover, delayed treatment increased lesion volumes in some cases. These results suggest that the NYU SCI model has a very short therapeutic window.