Skeletal Muscle Hypertrophy and Muscle Myostatin Reduction After Resistive Training in Stroke Survivors

Abstract

Background and Purpose-Stroke survivors experience disproportionate muscle atrophy and other detrimental tissue composition changes on the paretic side. The purpose was to determine whether myostatin levels are higher in paretic vs nonparetic muscle and the effects of resistive training (RT) on paretic and nonparetic mid-thigh muscle composition and myostatin mRNA expression in stroke survivors. Methods-Fifteen stroke survivors (50 -76 years) underwent bilateral multi-slice thigh CT scanning from the knee to the hip, bilateral vastus lateralis skeletal muscle tissue biopsies, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength test before and after a 12-week, (3 times/week) RT intervention. Results-Total body fat mass and fat-free mass did not change. Bilateral leg press and leg extension 1-repetition maximum strength increased 31% to 56% with RT (PϽ0.001). Paretic and nonparetic muscle area of the mid-thigh increased 13% (PϽ0.01) and 9% (PϽ0.05), respectively, after RT. Muscle attenuation of the mid-thigh increased 15% and 8% (both PϽ0.01) in the paretic and nonparetic thigh, respectively, representing reduced intramuscular fat. Muscle volume increased 14% (PϽ0.001) in the paretic thigh and 16% (PϽ0.05) in the nonparetic thigh after RT. Myostatin mRNA expression levels were 40% higher in the paretic than nonparetic muscle (Pϭ0.001) at baseline and decreased 49% in the paretic muscle (PϽ0.005) and 27% in the nonparetic muscle (Pϭ0.06) after RT. Conclusions-Progressive RT stimulates significant muscle hypertrophy and intramuscular fat reductions in disabled stroke survivors. The increased myostatin mRNA in the paretic thigh and reduction with RT imply an important regulatory role for myostatin after stroke. (Stroke. 2011;42:416-420.)

The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures

“…It should be appreciated that following SCI, muscle is paralyzed, and that there is little neuromuscular stimulation of muscle innervated by motor neurons originating in spinal segments below the level of the spinal cord injury. Following stroke, paralyzed muscle atrophies and expresses elevated levels of cytokines such as TNF-␣ and, potentially, myostatin, and increased neuromuscular activity attenuates these abnormalities (38,39). It may well be that similar abnormalities are present in paralyzed skeletal muscle after SCI; in support of this possibility, preliminary studies have indicated that in male rats, mRNA levels for TNF-␣ and IL-6 are elevated in gastrocnemius muscle after SCI.…”

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

“…studies of paralyzed muscle after stroke or nerve injury. In stroke patients, myostatin mRNA levels were increased in the vastus lateralis from the paretic versus non-paretic side and were reduced by resistance training (Ryan et al, 2011). In studies of rodents that have examined skeletal muscle after nerve transection or nerve crush, there have been persistent elevations of myostatin protein in some studies, but only a transient increase reported in others (Baumann et al, 2003;Lima et al, 2009).…”

“…Myostatin signals by binding the activin receptor IIB, ultimately resulting in phosphorylation and nuclear translocation of the transcription factors Smad2 and Smad3 (Glass, 2010). Myostatin mRNA levels have been reported to be increased in muscle paralyzed by stroke (Ryan et al, 2011). How myostatin levels and downstream signaling are altered after SCI is not well understood.…”

Bilateral Transcutaneous Electrical Nerve Stimulation Improves Lower‐Limb Motor Function in Subjects With Chronic Stroke: A Randomized Controlled Trial

“…The improvement in muscle strength after TOT could be attributed to an increase in muscle volume56 and recruitment of alternative neural substrate 57. Ryan and colleagues reported that 12 weeks of resistive training of the knee extensors increased the paretic thigh's cross‐sectional area and volume by ≈15% and increased the knee extension strength by 56% 56. Luft and colleagues57 reported that 6 months of treadmill exercise induced greater activation in multiple brain regions than passive stretching in subjects with stroke.…”