Molecular Changes in Sub-lesional Muscle Following Acute Phase of Spinal Cord Injury.
To clarify the molecular changes of sublesional muscle in the acute phase of spinal cord injury (SCI), a moderately severe injury (40 g cm) was induced in the spinal cord (T10 vertebral level) of adult male Sprague-Dawley rats (injury) and compared with sham (laminectomy only). Rats were sacrificed at 48 h (acute) post injury, and gastrocnemius muscles were excised. Morphological examination revealed no significant changes in the muscle fiber diameter between the sham and injury rats. Western blot analyses performed on the visibly red, central portion of the gastrocnemius muscle showed significantly higher expression of muscle specific E3 ubiquitin ligases (muscle ring finger-1 and muscle atrophy f-box) and significantly lower expression of phosphorylated Akt-1/2/3 in the injury group compared to the sham group. Cyclooxygenase 2, tumor necrosis factor alpha (TNF-α), and caspase-1, also had a significantly higher expression in the injury group; although, the mRNA levels of TNF-α and IL-6 did not show any significant difference between the sham and injury groups. These results suggest activation of protein degradation, deactivation of protein synthesis, and development of inflammatory reaction occurring in the sublesional muscles in the acute phase of SCI before overt muscle atrophy is seen.
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.
Nakul P
NP
Thakore
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.
Supriti
S
Samantaray
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.|Departmentof Physical Therapy, Kyungnam University, Changwon, South Korea.
Sookyoung
S
Park
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.|Division of Neuromuscular Disease, Department of Neurology, University of Alabama, Birmingham, AL, USA.
Kenkichi
K
Nozaki
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.
Joshua A
JA
Smith
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA.
April
A
Cox
Department of Health Sciences and Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA.
James
J
Krause
Department of Neurosurgery and Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, 309 CSB, MSC 606, Charleston, SC, 29425, USA. baniknl@musc.edu.|Ralph H. Johnson VA Medical Center, Charleston, SC, USA. baniknl@musc.edu.
Naren L
NL
Banik
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D018836:Inflammation Mediators
E3-ubiquitin ligases; Inflammation; Muscle atrophy; Protein degradation; Protein synthesis; Spinal cord injury