Two Experimental Strategies to Restore Muscle Mass in Adult Rats Following Spinal Cord Injury

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Abstract
Spinal cord injury decreases muscle mass and is associated with myofiber type trans formations in skeletal muscles. The present study evaluated the potential of motor- assisted cycling exercise or transplantation of fetal spinal cord tissue into the lesion cavity to inhibit or minimize these changes in skeletal muscles of 27 adult female Sprague-Dawley rats. Soleus (SO) and tibialis anterior (TA) muscles were studied 30 to 32 days after injury/intervention in the following groups: uninjured control ani mals (Con); spinal cord injured only (Tx); Tx with a 4-week exercise program con sisting of five weekly 60-minute sessions of cycling exercise initiated 5 days after in jury (TxEx); and Tx with fetal spinal cord tissue transplanted into the lesion cavity at the time of injury (TxTp). SO and TA muscle to body weight ratios were reduced significantly in the Tx group (24-30% decrease vs Con, p < 0.05) but were maintained with regular cycling exercise (6-8% decrease vs Con, no significant difference). The transplant had a beneficial effect on TA muscle mass (16% decrease vs Con, no sig nificant difference) but was not effective in limiting the effects of Tx on SO muscle mass. Immunohistochemistry and Northern analysis of TA and SO muscles revealed a Tx-induced reduction in myofiber cross sectional area (22% and 33% vs Con re spectively, p < 0.05) as well as a conversion in myosin heavy chain (MyHC) expres sion toward faster MyHC isoforms. Moreover, one month after injury, there was an increase in myofibers expressing more than one MyHC. mRNA encoding MyoD, a muscle-specific transcription factor, was increased in SO muscles suggesting that it may be involved in the long-term adaptations following spinal cord transection. Although cycling exercise was effective in preventing the decrease in myofiber area in both TA and SO, it did not inhibit the transformations of myofiber type. TA myofiber area was maintained in transplant recipients, however, this treatment was without conse quence on the size of SO myofibers. These results suggest that some of the normally observed spinal cord injury-induced skeletal muscle adaptations are minimized after one month of cycling exercise or fetal spinal cord tissue transplants. Key Words: Myosin heavy chain—Exercise—MyoD—Fetal tissue transplantation—Fiber types.