The present study is the first to show that resistive training results in lower extremity muscle hypertrophy and loss of intramuscular fat in stroke survivors. We utilized multi-slice CT imaging to make muscle volume determinations, representing the most comprehensive approach for assessing regional skeletal muscle hypertrophy. In addition, we provide the first evidence that myostatin mRNA expression are higher in the paretic muscle than the non-paretic muscle and that RT can reduce myostatin expression in stroke survivors. This suggests that myostatin is a key molecular regulator for paretic side muscle atrophy that can respond favorably to aggressive RT treatment interventions.
Numerous studies indicate that progressive resistance training is well tolerated and increases muscle strength in stroke survivors 21–25
. Our results confirm both the nature and magnitude of these RT-induced strength gains after stroke. Interestingly, we had similar relative improvements in leg press strength between the paretic and non-paretic legs, but the leg extension gains were almost a two-fold higher on the paretic side. This may have been attributed to the greater difference in strength between the two legs at baseline for the leg extension strength test. Alternatively, it may be indicative that factors unrelated to muscle mass (i.e. muscle quality) play a greater relative role in the strength adaptations related to open chain kinetic movements on the paretic side. Although we did not measure muscle power, other stroke studies have shown increases in lower body power after RT 24
. According to a recent meta-analysis of thirteen randomized controlled trials 26
, RT can also improve upper-limb strength and function.
Our functional outcome results are consistent with randomized and non-randomized trials that fail to show improvements in walking distance or gait velocity with RT 23, 25, 27
. Specifically, we did not see any changes in fastest or usual pace walking speed with RT. In contrast, circuit weight training that includes exercises specifically designed to improve gait and balance resulted in a greater distance walked in stroke subjects compared to control 28
. Yang et al. 21
also reported increased gait speed, stride length and six-minute walk distance after RT in stroke survivors compared to controls. Similarly, when progressive RT is combined with aerobic training, there are improvements in gait performance (6 min-walking speed) 29, 30
. Lastly, there is some evidence that progressive functional strength training in the sub-acute stroke recovery period involving weight bearing exercises may improve walking ability (speed) 31
and muscle strength of knee flexors 32
. Collectively, these studies suggest that RT alone may not change function but that hybrid interventions are effective and may work best to maximize the functional impact of RT after stroke.
The magnitude of hypertrophy with RT in stroke survivors is consistent with muscle hypertrophy after RT in healthy older individuals 4, 6
. Longer duration RT studies are needed to answer whether RT can further diminish the differences in paretic and non-paretic muscle area. We did not see significant changes in whole body fat-free mass by DXA after RT although others have reported increased FFM with RT in healthy elderly 5, 6, 33, 34
. This is likely because our RT protocol was limited to training the lower extremities, making whole body DXA not sufficiently sensitive enough to register the regional compositional change taking place in the thighs. Using multi-slice CT measurements of the thigh, we found significant comparable muscle hypertrophy across the thigh in the paretic and non-paretic thighs, demonstrating that the unilateral training was an effective stimulus for both legs. The atrophy in the paretic limb at baseline with subsequent hypertrophy of the muscle after the RT is encouraging and suggests that this type of exercise may be especially important in stroke survivors. Moreover, we observed an increase in muscle attenuation after RT in both paretic and non-paretic thighs indicating a loss of adipose tissue interspersedaround muscle. Muscle attenuation is associated with greater specific force production and muscular strength in elderly individuals of the Health ABC study 35
. In addition, there is augmented fat infiltration within muscle (reduced muscle attenuation) in obesity 36, 37
. RThas been shown to increase the attenuation of muscle and strength in elderly women 38
but this is the first account of larger and leaner muscle in stroke survivors.
Our results suggest that the myostatin cascade is a signaling pathway involved in post-stroke muscle atrophy. Myostatin is a negative key regulator of muscle mass as indicated in case studies of humans and animals 10–12
. Myostatin knockout mice have increased muscle mass accounted for by both increased muscle fiber size and number 9
. The hypertrophic effect of myostatin inhibition may be partly due to increased activity of satellite cells 39
. Our findings in the stroke model of atrophy in the paretic thigh compared to the non-paretic thigh coincide nicely with the significantly higher myostatin expression in the paretic limb than the non-paretic limb and provide indirect evidence that myostatin contributes to human muscle atrophy. Our RT intervention resulted in a significant decrease in myostatin mRNA levels in the paretic limb and approached significance in the non-paretic thigh. These results corroborate investigations in healthy adults where myostatin mRNA expression has been reported to decrease after resistance training 16
. We did not see changes in IGF-1 expression indicating that this is a less important regulator in the context of RT-related hypertrophy after stroke although other studies have shown it is important in healthy adults 40
. Future studies could examine additional growth factors and satellite cell proliferation in paretic and non-paretic muscle in regulating muscle growth with RT in chronic stroke.