Objectives: Spinal cord injury (SCI) results in early loss of skeletal muscle mass and function suggesting that any interventions must be started very soon after injury. The main objective of this study was to test the effects of Tamoxifen (a neuroprotective agent) on single muscle fiber size and function after SCI.
Design: Adult female rats were randomly assigned to either 7 days-sham (SHAM; n=5), 7 days-post-injury (7DPI; n=5), or Tamoxifen (TAM; n=4) group. SHAM animals were sutured after laminectomy. 7DPI rats received a contusion with an NYU impactor. Tamoxifen pellets (0.7mg daily) were implanted subcutaneously. Diameter and cross-sectional area (CSA) of chemically skinned soleus single muscle fibers were measured. Maximum force (Po), and specific force (Po/CSA) were determined by the slack test procedure using high calcium concentrations. 179 fibers were tested (69 SHAM; 55 7DPI; 55 TAM). Means + SD were calculated and values analyzed using ANOVA.
Results: Diameter was significantly (p< 0.001) smaller after 7 days in 7DPI (75 mm) and in TAM (81 mm) rats compared to SHAM (95 mm). Similar results (< 0.001) were seen for CSA (SHAM=3760 mm 2 ; 7DPI=3030 mm 2 ; TAM=2980 mm 2 ). Maximal force was significantly lower (p< 0.001) at 7DPI (83 mN) but there was no difference between SHAM (138mN) and TAM (110 mN) suggesting a beneficial effect of the drug. No difference among groups was seen in specific force (p=0.11; SHAM=5.5 N/cm 2 ; 7DPI=4.3 N/cm 2 ; TAM=5.3 N/cm 2 ).
Conclusions: Our results showed that muscle fiber size is smaller and single fiber function impaired in the acute phase. The reduction in force is due to muscle fiber atrophy only because single fiber specific force was similar in all three groups. Drug interventions such as tamoxifen after SCI can restore maximal force when implemented very early after injury.
Maria Santiago– Research Assistant, Unioversity of Puerto Rico School of Medicine
Jorge Monserrate– MSI, Unievrsity of Puerto Rico School of Medicine
Iris Salgado– Prof., University Central del Cartibe
Aranza Torrado– Research Associate, Unievrsity fo Puerto Rico
Sebastian Bernaschina– Mr., Unievrsity of Puerto Rico
Mariely Nieves– Researcher, University of Puerto Rico
Jorge Miranda– Professor, University fo Puerto Rico
Walter Frontera– Professor, University of Puerto Rico School of Medicine