Submitted on June 2, 2007
Accepted on August 19, 2007
REPAIR OF SPINAL CORD TRANSECTION AND ITS EFFECTS ON MUSCLE MASS AND MYOSIN HEAVY CHAIN ISOFORM PHENOTYPE
Yu-Shang Lee1, Ching-Yi Lin2, Vincent J. Caiozzo3, Richard T. Robertson2, Jen Yu4, and Vernon W. Lin5*
1 Physical Medicine & Rehabilitation, University of California, Irvine, Irvine, California, United States; Anatomy & Neurobiology, University of California, Irvine, Irvine, California, United States; VA Long Beach Healthcare System, Long Beach, California, United States
2 Anatomy & Neurobiology, University of California, Irvine, Irvine, California, United States
3 Department of Orthopaedics, University of California - Irvine, Irvine, California, United States; Physiology and Biophysics, University of California, Irvine, Irvine, California, United States
4 Physical Medicine & Rehabilitation, University of California, Irvine, Irvine, California, United States; Anatomy & Neurobiology, University of California, Irvine, Irvine, California, United States
5 Physical Medicine & Rehabilitation, University of California, Irvine, Irvine, California, United States; VA Long Beach Healthcare System, Long Beach, California, United States
* To whom correspondence should be addressed. E-mail: vernon.lin{at}va.gov.
A number of significant advances have been developed for treating spinal cord injury during the past two decades. The combination of peripheral nerve grafts and acidic fibroblast growth factor (hereafter referred to as PNG) has been shown to partially restore hindlimb function. However, very little is known about the effects of such treatments in restoring normal muscle phenotype. The primary goal of the current study was to test the hypothesis that PNG would completely/partially restore: i) muscle mass and muscle fiber cross-sectional area; and ii) the slow myosin heavy chain phenotype of the soleus muscle. To test this hypothesis, female Sprague-Dawley rats were assigned to three groups: i) sham control; ii) spinal cord transection (Tx); and iii) spinal cord transection plus PNG (Tx+PNG). Six months following spinal cord transection, the open-field test was performed to assess locomotory function, and then the soleus muscles were harvested and analyzed. SDS-PAGE for single muscle fiber was used to evaluate the MHC isoforms expression pattern following the injury and treatment. Immunohistochemistry was used to identify serotonin (5-HT) fibers in the spinal cord. When compared with the Tx, the Tx + PNG showed: i) significantly improved BBB scores (hind-limbs locomotion test); ii) less muscle atrophy; iii) a higher percentage of slow Type I fibers; and iv) 5-HT fibers distal to the lesion site. We conclude that the combined treatment of PNG is partially effective in restoring the muscle mass and slow phenotype of the soleus muscle in a T-8 spinal cord transected rat model.
