Skeletal muscle changes after hemiparetic stroke and potential beneficial effects of exercise intervention strategies

Abstract

Stroke is the leading cause of disability in the United States. New evidence reveals significant structural and metabolic changes in skeletal muscle after stroke. Muscle alterations include gross atrophy and shift to fast myosin heavy chain in the hemiparetic (contralateral) leg muscle; both are related to gait deficit severity. The underlying molecular mechanisms of this atrophy and muscle phenotype shift are not known. Inflammatory markers are also present in contralateral leg muscle after stroke. Individuals with stroke have a high prevalence of insulin resistance and diabetes. Skeletal muscle is a major site for insulin-glucose metabolism. Increasing evidence suggests that inflammatory pathway activation and oxidative injury could lead to wasting, altered function, and impaired insulin action in skeletal muscle. The health benefits of exercise in disabled populations have now been recognized. Aerobic exercise improves fitness, strength, and ambulatory performance in subjects with chronic stroke. Therapeutic exercise may modify or reverse skeletal muscle abnormalities.

Figures

Figure 1

Schematic overview of potential influences on skeletal muscle in individuals with chronic stroke.

Figure 2

Computed tomography (CT) images show atrophy of (a) paretic leg midthigh muscle area compared with (b) nonparetic thigh. Low-density CT lean-tissue imaging of same individual shows increased intramuscular fat content in (c) paretic compared with (d) nonparetic thigh after stroke.

Figure 3

Muscle tissue cross-sectional samples from (a) paretic and (b) nonparetic vastus lateralis (VL) muscle after stroke were stained with adenosine triphosphatase at pH 4.6. In paretic muscle, clear lack of slow-twitch myosin heavy chain (MHC) isoform (type I [dark]) fibers and relative atrophy of fast-twitch MHC isoform (type IIa [light] and type IIx [medium]) fibers were present compared with normal mosaic equal distribution of slow- and fast-twitch MHC isoform fibers in nonparetic VL muscle.

Figure 4

Silver-stained gel electrophoresis for slow- and fast-twitch myosin heavy chain (MHC) isoforms in paretic and nonparetic vastus lateralis muscles. (a) Rat extensor digitorum longus (predominantly fast-twitch MHC: upper band), (b) rat soleus (predominantly slow-twitch MHC: lower band), (c) and (f) hemiparetic limb of subject with stroke (absent slow-twitch MHC), and (d) and (e) nonparetic limb of subject with stroke (equal proportions of slow- and fast-twitch MHC).

Figure 5

Western Blot analysis of (a) fast- and (b) slow-twitch myosin heavy chain (MHC) isoforms shows significant reduction in total MHC in hemiparetic (HP) vastus lateralis muscle, with reduced level of fast-twitch MHC type IIx and slow-twitch MHC and no MHC type IIa isoform fibers compared with nonparetic leg (NP). After 6 months of treadmill aerobic exercise training (Post), significant increases in total MHC and proportions of slow-twitch MHC type I and fast-twitch oxidative MHC type IIa fibers with relative reduction in proportion of MHC type IIx fibers in paretic leg (Post HP) were noted.