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

2000 ◽  
Vol 279 (6) ◽  
pp. C1677-C1684 ◽  
Author(s):  
Esther E. Dupont-Versteegden ◽  
René J. L. Murphy ◽  
John D. Houlé ◽  
Cathy M. Gurley ◽  
Charlotte A. Peterson

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.

2003 ◽  
Vol 28 (3) ◽  
pp. 491-500 ◽  
Author(s):  
Chris M. Gregory ◽  
Krista Vandenborne ◽  
Michael J. Castro ◽  
G. Alton Dudley

Results of studies of rodent skeletal muscle plasticity are often extrapolated to humans. However, responses to "disuse" may be species specific, in part because of different inherent properties of anatomically similar muscles. Thus, this study quantified human and rat m. vastus lateralis (VL) fiber adaptations to 11 weeks of spinal cord injury (SCI). The m. VL was taken from 8 young (54 d) male Charles River rats after T-9 laminectomy (n = 4) or sham surgery (n = 4). In addition, the m. VL was biopsied in 7 able-bodied and in 7 SCI humans (31.3 ± 4.7 years, mean ± SE). Samples were sectioned and fibers were analyzed for type (I, IIa, IIb/x), cross-sectional area (CSA), succinate dehydrogenase (SDH), α-glycerol-phosphate dehydrogenase (GPDH), and actomyosin adenosine triphosphatase (qATPase) activities. Rat fibers had 1.5- to 2-fold greater SDH and GPDH activities while their fibers were 60% the size of those in humans. The most striking differences, however, were the absence of slow fibers in the rat and its four-fold greater proportion of IIb/x fibers (80% vs. 16% of the CSA) compared to humans. SCI decreased SDH activity more in rats whereas atrophy and IIa to IIb/x fiber shift occurred to a greater extent in humans. It is suggested that the rat is a reasonable model for studying the predominant response to SCI, atrophy. However, its high proportion of IIb/x fibers limits evaluation of the mechanical consequences of shifting to "faster" contractile machinery after SCI. Key words: enzyme, fiber type, disuse, biopsy


2015 ◽  
Vol 309 (9) ◽  
pp. R1101-R1111 ◽  
Author(s):  
Sophie Joanisse ◽  
Bryon R. McKay ◽  
Joshua P. Nederveen ◽  
Trisha D. Scribbans ◽  
Brendon J. Gurd ◽  
...  

The purpose of the present studies was to determine the effect of various nonhypertrophic exercise stimuli on satellite cell (SC) pool activity in human skeletal muscle. Previously untrained men and women (men: 29 ± 9 yr and women: 29 ± 2 yr, n = 7 each) completed 6 wk of very low-volume high-intensity sprint interval training. In a separate study, recreationally active men ( n = 16) and women ( n = 3) completed 6 wk of either traditional moderate-intensity continuous exercise ( n = 9, 21 ± 4 yr) or low-volume sprint interval training ( n = 10, 21 ± 2 yr). Muscle biopsies were obtained from the vastus lateralis before and after training. The fiber type-specific SC response to training was determined, as was the activity of the SC pool using immunofluorescent microscopy of muscle cross sections. Training did not induce hypertrophy, as assessed by muscle cross-sectional area, nor did the SC pool expand in any group. However, there was an increase in the number of active SCs after each intervention. Specifically, the number of activated (Pax7+/MyoD+, P ≤ 0.05) and differentiating (Pax7−/MyoD+, P ≤ 0.05) SCs increased after each training intervention. Here, we report evidence of activated and cycling SCs that may or may not contribute to exercise-induced adaptations while the SC pool remains constant after three nonhypertrophic exercise training protocols.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1872
Author(s):  
Shaowei Guo ◽  
Idan Redenski ◽  
Shulamit Levenberg

Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.


2021 ◽  
Vol 30 (9-10) ◽  
pp. 1394-1402
Author(s):  
De Gong ◽  
Yingmin Wang ◽  
Lirong Zhong ◽  
Mengmeng Jia ◽  
Ting Liu ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shaohui Zong ◽  
Gaofeng Zeng ◽  
Ye Fang ◽  
Jinzhen Peng ◽  
Yong Tao ◽  
...  

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.


2016 ◽  
Vol 39 (2) ◽  
pp. 180-189 ◽  
Author(s):  
Timo Hinrichs ◽  
Veronika Lay ◽  
Ursina Arnet ◽  
Inge Eriks-Hoogland ◽  
Hans Georg Koch ◽  
...  

Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.


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