Abstract
Objective:
Administration after spinal cord injury (SCI) of methylprednisolone (MP) for 24–48 h has been suggested to improve functional outcome. The safety of this approach has been questioned because of the known adverse effects of glucocorticoids on skeletal muscle and the immune system. The purpose of this study was to explicitly test adverse effects of regimen of MP administration on skeletal muscle.
Study design:
Male rats underwent spinal cord transection at T9-T10, followed by an intravenous injection of MP and subsequent infusion of MP for 24 h.
Results:
MP significantly reduced the weight of the triceps, soleus, plantaris and gastrocnemius muscles, with the greatest effect being a 63% decrease in triceps weight (for example, muscle above the level of lesion) at 7 days; below the level of lesion, gastrocnemius weight was reduced by 33% by SCI alone, and by 45% by SCI and MP. Centralized nuclei were found in myofibers of the gastrocnemius and triceps from the MP-SCI group, but not other groups. MP increased expression in the triceps, soleus and plantaris of FOXO1, MAFbx, MuRF1 and REDD1 at 1 day, and, in plantaris, at 7 days.
Conclusions:
Thus, 1 day of MP at a dose comparable to those routinely employed in clinical practice immediately after SCI resulted in marked atrophy of functionally intact muscle above the level of lesion, and worsened atrophy of paralyzed muscle below the level of lesion, associated with elevations in expression of four genes involved in pathways associated with muscle atrophy.
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Acknowledgements
The research reported here was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B4162C and B3347K).
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Wu, Y., Hou, J., Collier, L. et al. The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats. Spinal Cord 49, 867–873 (2011). https://doi.org/10.1038/sc.2011.28
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DOI: https://doi.org/10.1038/sc.2011.28
