Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury

Abstract

We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups (n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation (r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5'-Bromo-2'-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition.

Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy

“…Our data confirm that fibre nuclei/unit length correlates with fibre size and that changes in nuclear number usually parallel changes in fibre size (Chen et al, 2002;Dupont-Versteegden et al, 2000;Mitchell and Pavlath, 2001). In general, how changes in domain size and nuclear number are coordinated during fibre growth or atrophy is unknown.…”

“…This suggests that, at least in some atrophy models, proteolysis might cause atrophy by decreasing domain size prior to significant change in nuclear number. However, in general, changes in fibre size are accompanied by changes in nuclear number, implicating changes in nuclear turnover in fibre size control (Chen et al, 2002;Dupont-Versteegden et al, 2000;Mitchell and Pavlath, 2001). Thus, it is unclear whether a decline in fibre volume precedes or follows nuclear loss.…”

Methods to increase muscle tonus of upper airway to treat snoring: systematic review

“…Improvement of muscle tonus by physical training has been shown on several studies, and they were based on exercises for endurance and strength properties. This improvement was associated with increases in the proportion of Type I fiber and in the size of Type II fiber, demonstrated by muscle biopsy samples [42][43][44][45][46][47][48][49][50][51][52][53] . Methods to increase muscle tonus of the stomatognathic system are based on gain of endurance and strength properties either, so we considered this option as a possibility to increase the proportion of fiber Type I, resulting in decrease of snoring and clinical symptoms.…”

“…We know much more now about the pathogenesis of snoring and obstrutive sleep apnea (OSA), and some studies brought us evidences that the muscles in the pharynx are affected, showing fiber desproportion [38][39][40][41] . Based on such information, would be interesting to search for studies that have treated patients aiming to interfere with a diseased upper airway through out any sort of physical intervention to increase muscle tonus [42][43][44][45][46][47][48][49][50][51][52][53] . The aim of this systematic review is to evaluate if methods to increase muscle tonus of the upper airway is effective and safe for treatment of snoring based on accepted scientific evidence.…”

Estratégia terapêutica após contusão da medula espinhal: recuperação funcional e estabilidade cortical sensório-motora

“…Conseqüentemente, o controle voluntário dos músculos é eliminado, há ausência de descarga de peso nos membros afetados, o que leva a uma diminuição da área seccional do músculo (Castro et al, 1999;Gerrits et al, 1999;Dupont-Versteegden et al, 2000;Giangregorio e McCartney, 2006;Grumbles et al, 2009 (Riegger et al, 2007;Riegger et al, 2009;Popovich e McTigue, 2009). …”