Magnesium efficacy in a rat spinal cord injury model Laboratory investigation

Published: April 14, 2009  |  Source: thejns.org
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Object: 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.

Researchers: Diana Barrett Wiseman, M.D.*,1, Andrew T. Dailey, M.D.1,3, David Lundin, M.D.1, Jiegang Zhou, M.D.1, Adam Lipson, M.D.1, Alexis Falicov, M.D., Ph.D.2, and Christopher I. Shaffrey, M.D.4

1Departments of Neurological Surgery and 2Orthopaedics, University of Washington, Seattle, Washington; 3Department of Neurosurgery, University of Utah, Salt Lake City, Utah; and 4Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia

Abbreviations used in this paper: ANOVA = analysis of variance; BBB = Basso-Beattie-Bresnahan; LFB = Luxol fast blue; NASCIS = National Acute Spinal Cord Injury Studies; NMDA = N-methyl-d-aspartate; SCI = spinal cord injury; TBI = traumatic brain injury.

Address correspondence to: Andrew Dailey, M.D., Department of Neurosurgery, University of Utah, 175 North Medical Drive, Salt Lake City, Utah 84132.

* Drs. Wiseman and Dailey contributed equally to this work.

DOI: 10.3171/spi.2009.10.4.308