Therapeutic time window for methylprednisolone in spinal cord injured rat.
Recent clinical trials have reported that methylprednisolone sodium succinate administered within 8 hours improves neurological recovery in human spinal cord injury (SCI). Methylprednisolone, however, was ineffective and possibly even deleterious when given more than 8 hours after injury. This finding suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone treatment for optimal neuroprotection, a single or two bolus dose of methylprednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. after three graded spinal cord injury. The primary outcome measure was 24-hour 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 significantly reduced 24-hour lesion volumes in injured rat spinal cords. However, any other methylprednisolone treatment starting 30 min. or more after injury 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.
Yoon
D H
DH
Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea. ydoheum@yumc.yonsei.ac.kr
Kim
Y S
YS
Young
W
W
D000818:Animals; D004334:Drug Administration Schedule; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D018696:Neuroprotective Agents; D008776:Methylprednisolone Hemisuccinate