Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 98, Issue 5, Pages 843-868Publisher
WILEY
DOI: 10.1002/jnr.24564
Keywords
androgen; estradiol; exercise; hypogonadism; neuromuscular plasticity; osteoporosis; physical rehabilitation; regenerative rehabilitation; RRID; AB_2235587; RRID; AB_1157865; RRID; AB_1157897; RRID; AB_138404; RRID; AB_1500896; RRID; AB_2099233; RRID; AB_2147165; RRID; AB_2556551; RRID; AB_330924; RRID; AB_60395; RRID; AB_881987
Categories
Funding
- National Institutes of Health [P01 HD059751-01A1]
- U.S. Department of Veterans Affairs [1I21RX001273-01, 1I50RX002020-1, B9280-O]
- Paralyzed Veterans of America Research Foundation [2939]
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Loading and testosterone may influence musculoskeletal recovery after spinal cord injury (SCI). Our objectives were to determine (a) the acute effects of bodyweight-supported treadmill training (TM) on hindlimb cancellous bone microstructure and muscle mass in adult rats after severe contusion SCI and (b) whether longer-term TM with adjuvant testosterone enanthate (TE) delivers musculoskeletal benefit. In Study 1, TM (40 min/day, 5 days/week, beginning 1 week postsurgery) did not prevent SCI-induced hindlimb cancellous bone loss after 3 weeks. In Study 2, TM did not attenuate SCI-induced plantar flexor muscles atrophy nor improve locomotor recovery after 4 weeks. In our main study, SCI produced extensive distal femur and proximal tibia cancellous bone deficits, a deleterious slow-to-fast fiber-type transition in soleus, lower muscle fiber cross-sectional area (fCSA), impaired muscle force production, and levator ani/bulbocavernosus (LABC) muscle atrophy after 8 weeks. TE alone (7.0 mg/week) suppressed bone resorption, attenuated cancellous bone loss, constrained the soleus fiber-type transition, and prevented LABC atrophy. In comparison, TE+TM concomitantly suppressed bone resorption and stimulated bone formation after SCI, produced near-complete cancellous bone preservation, prevented the soleus fiber-type transition, attenuated soleus fCSA atrophy, maintained soleus force production, and increased LABC mass. 75% of SCI+TE+TM animals recovered voluntary over-ground hindlimb stepping, while no SCI and only 20% of SCI+TE animals regained stepping ability. Positive associations between testosterone and locomotor function suggest that TE influenced locomotor recovery. In conclusion, short-term TM alone did not improve bone, muscle, or locomotor recovery in adult rats after severe SCI, while longer-term TE+TM provided more comprehensive musculoskeletal benefit than TE alone.
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