Yonsei Med J.  1999 Aug;40(4):313-320. 10.3349/ymj.1999.40.4.313.

Therapeutic time window for methylprednisolone in spinal cord injured rat

• Yoon DH
• Kim YS
• Young W

• KMID: 711655
• DOI: http://doi.org/10.3349/ymj.1999.40.4.313

Abstract

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.

Keyword

Methylprednisolone; spinal cord injury; therapeutic time window

MeSH Terms

Animal
Drug Administration Schedule
Male
Methylprednisolone Hemisuccinate/therapeutic use
Methylprednisolone Hemisuccinate/administration & dosage*
Neuroprotective Agents/therapeutic use
Neuroprotective Agents/administration & dosage*
Rats
Rats, Long-Evans
Spinal Cord/pathology
Spinal Cord Injuries/pathology
Spinal Cord Injuries/drug therapy*