Hindlimb Muscle Morphology and Function in a New Atrophy Model Combining Spinal Cord Injury and Cast Immobilization

University of Florida, Physical Therapy, Gainesville, Florida, United States
Journal of neurotrauma (Impact Factor: 3.71). 09/2012; 30(3). DOI: 10.1089/neu.2012.2504
Source: PubMed


Contusion spinal cord injury (SCI) animal models are used to study loss of muscle function and mass. However, parallels to the human condition typically have been confounded by spontaneous recovery observed within the first few post-injury weeks, partly due to free cage activity. We implemented a new rat model combining SCI with cast immobilization (IMM) to more closely reproduce the unloading conditions experienced by SCI patients. Magnetic resonance imaging was used to monitor hindlimb muscles cross-sectional area (CSA) after SCI, IMM alone, SCI combined with IMM (SCI+IMM) and in controls (CTR) over a period of 21 days. Soleus muscle tetanic force was measured in situ on day 21, and hindlimb muscles harvested for histology. IMM alone produced a decrease in triceps surae CSA to 63.9±4.9% of baseline values within 14 days. In SCI, CSA decreased to 75±10.5% after 7 days, and recovered to 77.9±10.7% by day 21. SCI+IMM showed the greatest amount of atrophy (56.9±9.9 % on day 21). In all groups, muscle mass and soleus tetanic force decreased in parallel, such that specific force was maintained. EDL and soleus fiber size decreased in all groups, particularly in SCI+IMM. We observed a significant degree of asymmetry in muscle CSA in SCI but not IMM. This effect increased between day 7 and 21 in SCI, but also in SCI+IMM, suggesting a minor dependence on muscle activity. SCI+IMM offers a clinically relevant model of SCI to investigate the mechanistic basis for skeletal muscle adaptations after SCI and develop therapeutic approaches.

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Available from: Fan Ye, Jul 15, 2014
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    • "), bed rest (Berg et al. 2007; Akima et al. 2001; Bamman and Clarke 1998; Berg et al. 1997; Widrick et al. 1997; Narici and Maganaris 2007; Trappe et al. 2004a), Immobilization (Ye et al. 2013; Psatha et al. 2012; Yasuda et al. 2005; Oliveira Milani et al. 2008; D'Antona et al. 2003; Gibson et al. 1987), Microgravity (Fitts et al. 2010; Widrick et al. 1999; Caiozzo et al. 1996; Edgerton et al. 1995) Sarcomeres in parallel ↓ (Bamman and Clarke 1998; Berg et al. 1997; Yasuda et al. 2005; Fitts et al. 2010; Widrick et al. 1999, 1997; Gibson et al. 1987; Deschenes 2001) a , (Narici and Maganaris 2007) Faster MHC ↑ (Andersen and Aagaard 2000; Caiozzo et al. 1996; D'Antona et al. 2003; Zhou et al. 1995), NC (Hanson et al. 2012; Bamman and Clarke 1998; Berg et al. 1997) Titin length ↓ (Kasper and Xun 2000), density ↓ (Kasper and Xun 2000; Toursel et al. 2002), elasticity ↓ (Goto et al. 2003) Fiber CSA ↓ (Bamman and Clarke 1998; Berg et al. 1997; Yasuda et al. 2005; Fitts et al. 2010; Widrick et al. 1999, 1997; Gibson et al. 1987; Deschenes 2001), Slow only (Hanson et al. 2012; Allen and Linderman 1997) Fiber F max /CSA ↓ (Widrick et al. 1999, 2002, 1997; Trappe et al. 2004a; D'Antona et al. 2003; Pansarasa et al. 2009) Faster fiber type ↑ (Canon and Goubel 1995; Caiozzo et al. 1996; D'Antona et al. 2003; Edgerton et al. 1995), NC (Yasuda et al. 2005; Berg et al. 1997; Bamman and Clarke 1998) Passive stiffness NC (Oliveira Milani et al. 2008) Anat. CSA ↓ (Campbell et al. 2013; Seynnes et al. 2008; de Boer et al. 2007a; Berg et al. 2007; Akima et al. 2001; Psatha et al. 2012; Yasuda et al. 2005) Volume ↓ (Campbell et al. 2013; Seynnes et al. 2008; Psatha et al. 2012) Pennation angle ↓ (Campbell et al. 2013; Seynnes et al. 2008; de Boer et al. 2007a; Psatha et al. 2012) Fascicle length ↓ (Campbell et al. 2013; Seynnes et al. 2008; de Boer et al. 2007a) Anat. "
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    ABSTRACT: Skeletal muscle undergoes continuous turnover to adapt to changes in its mechanical environment. Overload increases muscle mass, whereas underload decreases muscle mass. These changes are correlated with, and enabled by, structural alterations across the molecular, subcellular, cellular, tissue, and organ scales. Despite extensive research on muscle adaptation at the individual scales, the interaction of the underlying mechanisms across the scales remains poorly understood. Here, we present a thorough review and a broad classification of multiscale muscle adaptation in response to a variety of mechanical stimuli. From this classification, we suggest that a mathematical model for skeletal muscle adaptation should include the four major stimuli, overstretch, understretch, overload, and underload, and the five key players in skeletal muscle adaptation, myosin heavy chain isoform, serial sarcomere number, parallel sarcomere number, pennation angle, and extracellular matrix composition. Including this information in multiscale computational models of muscle will shape our understanding of the interacting mechanisms of skeletal muscle adaptation across the scales. Ultimately, this will allow us to rationalize the design of exercise and rehabilitation programs, and improve the long-term success of interventional treatment in musculoskeletal disease.
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    • "Skeletal muscle is a highly dynamic tissue, capable of continuous remodelling in response to various environmental stimuli (Adams, 2002). It is widely recognized that conditions of unloading, such as limb immobilization or microgravity, result in the loss of muscle mass and strength (Booth, 1982; Mitchell & Pavlath, 2001; Ye et al. 2012). On the contrary, atrophied muscles can regain their functional performance when returned to normal loading conditions or with training, although this process is often slow and incomplete (Witzmann et al. 1982; Nilsson et al. 2003). "
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