title: The administration of high-dose methylprednisolone for 24 h reduced muscle size and increased atrophy-related gene expression in spinal cord-injured rats.
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.
  
  
  METHODS
  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.
authors: Department of Veterans Affairs, Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J Peters VA Medical Center, Bronx, NY 10468, USA.
authors: Y
authors: Y
authors: Wu
authors: J
authors: J
authors: Hou
authors: L
authors: L
authors: Collier
authors: J
authors: J
authors: Pan
authors: L
authors: L
authors: Hou
authors: W
authors: W
authors: Qin
authors: W A
authors: WA
authors: Bauman
authors: C P
authors: CP
authors: Cardozo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D051858:Forkhead Transcription Factors; D008775:Methylprednisolone; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012097:Repressor Proteins; D044843:SKP Cullin F-Box Protein Ligases; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C000632146:Ddit4 protein, rat; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C486692:Fbxo32 protein, rat; C499086:Trim63 protein, rat