Human and Rat Skeletal Muscle Adaptations to Spinal Cord Injury

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

2016 ◽  
Vol 48 ◽  
pp. 894
Author(s):  
Rodney C. Wade ◽  
Ashraf S. Gorgey ◽  
Jennifer Hubert ◽  
Ryan Sumrell ◽  
Justin Bengel ◽  
...  

1989 ◽  
Vol 66 (5) ◽  
pp. 2454-2461 ◽  
Author(s):  
H. J. Green ◽  
J. R. Sutton ◽  
A. Cymerman ◽  
P. M. Young ◽  
C. S. Houston

Adaptations in skeletal muscle in response to progressive hypobaria were investigated in eight male subjects [maximal O2 uptake = 51.2 +/- 3.0 (SE) ml.kg-1.min-1] over 40 days of progressive decompression to the stimulated altitude of the summit of Mt. Everest. Samples of the vastus lateralis muscle extracted before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) indicated that maximal activities of enzymes representative of the citric acid cycle, beta-oxidation, glycogenolysis, glycolysis, glucose phosphorylation, and high-energy phosphate transfer were unchanged (P greater than 0.05) at 380 and 282 Torr over initial SL-1 values. After exposure to 282 Torr, however, representing an additional period of approximately 7 days, reductions (P less than 0.05) were noted in succinic dehydrogenase (21%), citrate synthetase (37%), and hexokinase (53%) between SL-2 and 380 Torr. No changes were found in the other enzymes. Capillarization as measured by the number of capillaries per cross-sectional area (CC/FA) was increased (P less than 0.05) in both type I (0.94 +/- 0.8 vs. 1.16 +/- 0.05) and type II (0.84 +/- 0.07 vs. 1.05 +/- 0.08) fibers between SL-1 and SL-2. This increase was mediated by a reduction in fiber area. No changes were found in fiber-type distribution (type I vs. type II). These findings do not support the hypothesis, at least in humans, that, at the level of the muscle cell, extreme hypobaric hypoxia elicits adaptations directed toward maximizing oxidative function.


2013 ◽  
Vol 305 (9) ◽  
pp. E1071-E1080 ◽  
Author(s):  
Emil Kostovski ◽  
Hanneke Boon ◽  
Nils Hjeltnes ◽  
Leonidas S. Lundell ◽  
Maria Ahlsén ◽  
...  

AMP-activated protein kinase (AMPK) is a pivotal regulator of energy homeostasis. Although downstream targets of AMPK are widely characterized, the physiological factors governing isoform expression of this protein kinase are largely unknown. Nerve/contractile activity has a major impact on the metabolic phenotype of skeletal muscle, therefore likely to influence AMPK isoform expression. Spinal cord injury represents an extreme form of physical inactivity, with concomitant changes in skeletal muscle metabolism. We assessed the influence of longstanding and recent spinal cord injury on protein abundance of AMPK isoforms in human skeletal muscle. We also determined muscle fiber type as a marker of glycolytic or oxidative metabolism. In subjects with longstanding complete injury, protein abundance of the AMPKγ3 subunit, as well as myosin heavy chain (MHC) IIa and IIx, were increased, whereas abundance of the AMPKγ1 subunit and MHC I were decreased. Similarly, abundance of AMPKγ3 and MHC IIa proteins were increased, whereas AMPKα2, -β1, and -γ1 subunits and MHC I abundance was decreased during the first year following injury, reflecting a more glycolytic phenotype of the skeletal muscle. However, in incomplete cervical lesions, partial recovery of muscle function attenuated the changes in the isoform profile of AMPK and MHC. Furthermore, exercise training (electrically stimulated leg cycling) partly normalized mRNA expression of AMPK isoforms. Thus, physical activity affects the relative expression of AMPK isoforms. In conclusion, skeletal muscle abundance of AMPK isoforms is related to physical activity and/or muscle fiber type. Thus, physical/neuromuscular activity is an important determinant of isoform abundance of AMPK and MCH. This further underscores the need for physical activity as part of a treatment regimen after spinal cord injury to maintain skeletal muscle metabolism.


2016 ◽  
Vol 310 (9) ◽  
pp. E754-E761 ◽  
Author(s):  
Ceren Yarar-Fisher ◽  
C. Scott Bickel ◽  
Neil A. Kelly ◽  
Michael J. Stec ◽  
Samuel T. Windham ◽  
...  

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Isley Jesus ◽  
Pauline Michel-Flutot ◽  
Therese B. Deramaudt ◽  
Alexia Paucard ◽  
Valentin Vanhee ◽  
...  

AbstractCervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Juanjuan Fu ◽  
Hongxing Wang ◽  
Lingxiao Deng ◽  
Jianan Li

The exercise training is an effective therapy for spinal cord injury which has been applied to clinic. Traditionally, the exercise training has been considered to improve spinal cord function only through enhancement, compensation, and replacement of the remaining function of nerve and muscle. Recently, accumulating evidences indicated that exercise training can improve the function in different levels from end-effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex. We compiled published data collected in different animal models and clinical studies into a succinct review of the current state of knowledge.


1999 ◽  
Vol 86 (1) ◽  
pp. 350-358 ◽  
Author(s):  
Michael J. Castro ◽  
David F. Apple ◽  
Robert S. Staron ◽  
Gerson E. R. Campos ◽  
Gary A. Dudley

This study examined the influence of spinal cord injury (SCI) on affected skeletal muscle. The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinically stable (average 6 wk after SCI), and 11 and 24 wk after injury. Samples were also taken from nine able-bodied controls at two time points 18 wk apart. Surface electrical stimulation (ES) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals. Biopsies were analyzed for fiber type percent and cross-sectional area (CSA), fiber type-specific succinic dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (GPDH) activities, and myosin heavy chain percent. Controls showed no change in any variable over time. Patients showed 27–56% atrophy ( P = 0.000) of type I, IIa, and IIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSA approximately one-third that of controls. Their fiber type specific SDH and GPDH activities increased ( P ≤ 0.001) from 32 to 90% over the 18 wk, thereby approaching or surpassing control values. The relative CSA of type I fibers and percentage of myosin heavy chain type I did not change. There was apparent conversion among type II fiber subtypes; type IIa decreased and type IIax+IIx increased ( P ≤ 0.012). Force loss during ES did not change over time for either group but was greater ( P = 0.000) for SCI patients than for controls overall (27 vs. 9%). The results indicate that vastus lateralis muscle shows marked fiber atrophy, no change in the proportion of type I fibers, and a relative independence of metabolic enzyme levels from activation during the first 24 wk after clinically complete SCI. Over this time, quadriceps femoris muscle showed moderately greater force loss during ES in patients than in controls. It is suggested that the predominant response of mixed human skeletal muscle within 6 mo of SCI is loss of contractile protein. Therapeutic interventions could take advantage of this to increase muscle mass.


2000 ◽  
Vol 88 (4) ◽  
pp. 1321-1326 ◽  
Author(s):  
Walter R. Frontera ◽  
Virginia A. Hughes ◽  
Roger A. Fielding ◽  
Maria A. Fiatarone ◽  
William J. Evans ◽  
...  

The present study examines age-related changes in skeletal muscle size and function after 12 yr. Twelve healthy sedentary men were studied in 1985–86 (T1) and nine (initial mean age 65.4 ± 4.2 yr) were reevaluated in 1997–98 (T2). Isokinetic muscle strength of the knee and elbow extensors and flexors showed losses ( P < 0.05) ranging from 20 to 30% at slow and fast angular velocities. Computerized tomography ( n = 7) showed reductions ( P < 0.05) in the cross-sectional area (CSA) of the thigh (12.5%), all thigh muscles (14.7%), quadriceps femoris muscle (16.1%), and flexor muscles (14.9%). Analysis of covariance showed that strength at T1 and changes in CSA were independent predictors of strength at T2. Muscle biopsies taken from vastus lateralis muscles ( n = 6) showed a reduction in percentage of type I fibers (T1 = 60% vs. T2 = 42%) with no change in mean area in either fiber type. The capillary-to-fiber ratio was significantly lower at T2 (1.39 vs. 1.08; P = 0.043). Our observations suggest that a quantitative loss in muscle CSA is a major contributor to the decrease in muscle strength seen with advancing age and, together with muscle strength at T1, accounts for 90% of the variability in strength at T2.


Sports ◽  
2019 ◽  
Vol 7 (7) ◽  
pp. 169 ◽  
Author(s):  
Kevin M. Carroll ◽  
Caleb D. Bazyler ◽  
Jake R. Bernards ◽  
Christopher B. Taber ◽  
Charles A. Stuart ◽  
...  

The purpose of the study was to compare the physiological responses of skeletal muscle to a resistance training (RT) program using repetition maximum (RM) or relative intensity (RISR). Fifteen well-trained males underwent RT 3 d·wk−1 for 10 weeks in either an RM group (n = 8) or RISR group (n = 7). The RM group achieved a relative maximum each day, while the RISR group trained based on percentages. The RM group exercised until muscular failure on each exercise, while the RISR group did not reach muscular failure throughout the intervention. Percutaneous needle biopsies of the vastus lateralis were obtained pre-post the training intervention, along with ultrasonography measures. Dependent variables were: Fiber type-specific cross-sectional area (CSA); anatomical CSA (ACSA); muscle thickness (MT); mammalian target of rapamycin (mTOR); adenosine monophosphate protein kinase (AMPK); and myosin heavy chains (MHC) specific for type I (MHC1), type IIA (MHC2A), and type IIX (MHC2X). Mixed-design analysis of variance and effect size using Hedge’s g were used to assess within- and between-group alterations. RISR statistically increased type I CSA (p = 0.018, g = 0.56), type II CSA (p = 0.012, g = 0.81), ACSA (p = 0.002, g = 0.53), and MT (p < 0.001, g = 1.47). RISR also yielded a significant mTOR reduction (p = 0.031, g = −1.40). Conversely, RM statistically increased only MT (p = 0.003, g = 0.80). Between-group effect sizes supported RISR for type I CSA (g = 0.48), type II CSA (g = 0.50), ACSA (g = 1.03), MT (g = 0.72), MHC2X (g = 0.31), MHC2A (g = 0.87), and MHC1 (g = 0.59); with all other effects being of trivial magnitude (g < 0.20). Our results demonstrated greater adaptations in fiber size, whole-muscle size, and several key contractile proteins when using RISR compared to RM loading paradigms.


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