Magnesium efficacy in a rat spinal cord injury model.
OBJECTIVE
Magnesium has been shown to have neuroprotective properties in short-term spinal cord injury (SCI) studies. The authors evaluated the efficacy of magnesium, methylprednisolone, and magnesium plus methylprednisolone in a rat SCI model.


METHODS
A moderate-to-severe SCI was produced at T9-10 in rats, which then received saline, magnesium, methylprednisolone, or magnesium plus methylprednisolone within 10 minutes of injury. The Basso-Beattie-Bresnahan (BBB) motor score was evaluated weekly, beginning on postinjury Day 1. After 4 weeks, the rats' spinal cords were evaluated histologically to determine myelin index and gross white matter sparing. A second experiment was conducted to evaluate the effect of delayed administration (8, 12, or 24 hours postinjury) of magnesium on recovery.


RESULTS
The mean BBB scores at 4 weeks showed that rats in which magnesium was administered (BBB Score 6.9 +/- 3.9) recovered better than controls (4.2 +/- 2.0, p < 0.01). Insufficient numbers of animals receiving methylprednisolone were available for analysis because of severe weight loss. The rats given magnesium within 8 hours of injury had better motor recovery at 4 weeks than control animals (13.8 +/- 3.7 vs 8.6 +/- 5.1, p < 0.01) or animals in which magnesium was administered at 12 or 24 hours after injury (p < 0.01). Steroids (30.2%), magnesium (32.3%), and a combination of these (42.3%) had a significant effect on white matter sparing (p < 0.05), but the effect was not synergistic (p > 0.8). Neither steroids nor magnesium had a significant effect on the myelin index (p > 0.1).


CONCLUSIONS
The rats receiving magnesium had significantly better BBB motor scores and white matter sparing 4 weeks after moderate-to-severe SCI than control animals. In addition, the groups given steroids only or magnesium and steroids had improved white matter sparing, although the limited numbers of animals reaching the study end point makes it difficult to draw firm conclusions about the utility of steroids in this model. The optimal timing of magnesium administration appears to be within 8 hours of injury.
Department of Neurological Surgery, University of Washington, Seatle, Washington, USA.
Diana Barrett
DB
Wiseman
Andrew T
AT
Dailey
David
D
Lundin
Jiegang
J
Zhou
Adam
A
Lipson
Alexis
A
Falicov
Christopher I
CI
Shaffrey
D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D008274:Magnesium / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D015431:Weight Loss / Q000187:drug effects
D018696:Neuroprotective Agents; D008274:Magnesium; D008775:Methylprednisolone