Spastic Tail Muscles Recover From Myofiber Atrophy and Myosin Heavy Chain Transformations in Chronic Spinal Rats

Abstract

Harris RL, Putman CT, Rank M, Sanelli L, Bennett DJ. Spastic tail muscles recover from myofiber atrophy and myosin heavy chain transformations in chronic spinal rats. J Neurophysiol 97: 1040 -1051, 2007. First published November 22, 2006; doi:10.1152/jn.00622.2006. Without intervention after spinal cord injury (SCI), paralyzed skeletal muscles undergo myofiber atrophy and slow-to-fast myofiber type transformations. We hypothesized that chronic spasticity-associated neuromuscular activity after SCI would promote recovery from such deleterious changes. We examined segmental tail muscles of chronic spinal rats with longstanding tail spasticity (7 mo after sacral spinal cord transection; older chronic spinals), chronic spinal rats that experienced less spasticity early after injury (young chronic spinals), and rats without spasticity after transection and bilateral deafferentation (spinal isolated). These were compared with tail muscles of age-matched normal rats. Using immunohistochemistry, we observed myofiber distributions of 15.9 Ϯ 3.5% type I, 18.7 Ϯ 10.7% type IIA, 60.8 Ϯ 12.6% type IID(X), and 2.3 Ϯ 1.3% type IIB (means Ϯ SD) in young normals, which were not different in older normals. Young chronic spinals demonstrated transformations toward faster myofiber types with decreased type I and increased type IID(X) paralleled by atrophy of all myofiber types compared with young normals. Spinal isolated rats also demonstrated decreased type I myofiber proportions and increased type II myofiber proportions, and severe myofiber atrophy. After 4 mo of complete spasticity (older chronic spinals), myofiber type transformations were reversed, with no significant differences in type I, IIA, IID(X), or IIB proportions compared with age-matched normals. Moreover, after this prolonged spasticity, type I, IIA, and IIB myofibers recovered from atrophy, and type IID(X) myofibers partially recovered. Our results indicate that early after transection or after long-term spinal isolation, relatively inactive tail myofibers atrophy and transform toward faster myofiber types. However, long-term spasticity apparently produces neuromuscular activity that promotes recovery of myofiber types and myofiber sizes.

Insulin growth factors may explain relationship between spasticity and skeletal muscle size in men with spinal cord injury

“…Spasticity is a velocity-dependent phenomenon characterized by increased muscle tone in response to passive movement. Spasticity has been previously shown to preserve slow-to-fast fiber conversion in the tail muscle of SCI rats [19]. As early as 6 weeks post-SCI, spasticity appears to exert a protective effect on skeletal muscle size and composition in those with a high level of injury compared with nonspastic individuals with a low level of injury [8].…”

Severe spasticity in lower extremities is associated with reduced adiposity and lower fasting plasma glucose level in persons with spinal cord injury

“…First, spastic muscles might attenuate the shift in slow-to-fast muscle fiber transformation; slow fibers have a higher mitochondrial concentration that may be responsible for the increased fat oxidation. 22,23 Second, SCI is characterized by diminished growth hormone (GH), insulin-like growth factor-1 (IGF-1) and testosterone; the decline in anabolic hormones may further exacerbate muscle atrophy and FM gain below the level of injury. [24][25][26] Spasticity may provoke muscular IGF-1 that compensates for the reduced growth hormone-IGF-1 axis after SCI.…”

“…In addition, mechanisms through which severe spasticity ameliorates the derangement of body compositions and glucose homeostasis could be investigated. For example, differences in the expression of glucose transport protein, GLUT4 proteins, 30 IGF-1 concentration 7,29 and muscle fiber type composition 22,23 have been suggested as related mechanisms.…”

Demystifying Spasticity: Reply to Dietz

“…It is sometimes even quite the opposite. Indeed, we have recently shown that neuronal activity in the form of muscle spasms actually prevents muscle atrophy and changes in muscle properties (Harris et al 2006(Harris et al , 2007. So the nonspasming muscles atrophy and the spasming muscles do not atrophy, which raises the question of how vigorously we should treat spasticity with drugs like baclofen (Li et al 2004c).…”

“…Dietz dismisses all the animal models, especially our sacral spinal rat, because he thinks that they do not have changes in muscle properties similar to those seen in his stroke patient groups (Dietz 2007;Dietz and Sinkjaer 2007). Ironically, however, it is our sacral spinal rat model that might be most useful to his investigations of muscle properties (Harris et al 2006(Harris et al , 2007 because we have shown that the muscle properties of sacral spinal rats do change very much as in humans after spinal cord injury (Thomas and Ross 1997;Zijdewind and Thomas 2003). Interesting, in muscles that exhibit lots of spasms, this motoneural activity tends to help preserve muscle properties, preventing atrophy, although not completely preventing increased contractures (Harris et al 2006(Harris et al , 2007.…”