Muscle molecular phenotype after stroke is associated with gait speed

Deyne, Patrick G. De; Hafer‐Macko, Charlene E.; Ivey, Frederick M.; Ryan, Alice S.; Macko, Richard F.

doi:10.1002/mus.20085

Cited by 96 publications

(120 citation statements)

References 36 publications

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“…In addition, transcript levels for glycerol-3-phosphate dehydrogenase 2 (GPD2), which is integral to muscle glycolysis, are significantly elevated in the paretic compared with the nonparetic leg. These findings are consistent with evidence based on muscle MHC isoform profiles that show that paretic leg skeletal muscle shifts to fast-twitch muscle fibers with increased reliance on anaerobic metabolism during single-leg exercise after stroke [3,12]. Prior muscle biology studies have demonstrated plasticity of muscle fiber composition and enzymatic activity that depend on the specific task requirements of individual muscles [21]; physical activity level [22]; and stimulus applied to the muscle, such as electrical stimulation [20].…”

Section: Discussionsupporting

confidence: 82%

“…Gross muscular atrophy predicts reduced cardiovascular fitness levels after stroke [23]. The shift to a fast MHC isoform in the hemiparetic leg is inversely related to a neurological deficit indexed by walking speed; individuals with the greatest shift in fast MHC isoforms had the slowest gait speeds [3]. Physical inactivity or detraining and muscle unloading have been previously reported to lead to a fiber type transition from slow oxidative to fast nonoxidative fibers [24][25][26].…”

Section: Discussionmentioning

confidence: 99%

“…Hemiparesis is the most common neurological sequela. Skeletal muscle has recently been recognized as a site of secondary biological change after stroke that may propagate the functional decline and contribute to the increased risk of insulin resistance, cardiovascular disease, and recurrent stroke [2][3][4][5][6][7]. A number of pathophysiological mechanisms underlie the biological changes in muscle in stroke survivors.…”

Section: Introductionmentioning

confidence: 99%

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Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke

McKenzie

Yu²,

Macko³

et al. 2008

JRRD

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Hemiparetic stroke leads to major skeletal muscle abnormalities, as illustrated by paretic leg atrophy, weakness, and spasticity. Furthermore, the hemiparetic limb muscle shifts to a fast-twitch muscle fiber phenotype with anaerobic metabolism. This study investigated whether skeletal muscle genes were altered in chronic hemiparetic stroke. The nonparetic leg muscle served as an internal control. We used Affymetrix microarray analysis to survey gene expression differences between paretic and nonparetic vastus lateralis muscle punch biopsies from 10 subjects with chronic hemiparetic stroke. Stroke latency was greater than 6 months. We found that 116 genes were significantly altered between the paretic and nonparetic vastus lateralis muscles. These gene differences were consistent with reported differences after stroke in areas such as injury and inflammation markers, the myosin heavy chain profile, and high prevalence of impaired glucose tolerance and type 2 diabetes. Furthermore, while many other families of genes were altered, the gene families with the most genes altered included inflammation, cell cycle regulation, signal transduction, metabolism, and muscle contractile protein genes. This study is an early step toward identification of specific gene regulatory pathways that might lead to these differences, propagate disability, and increase vascular disease risk.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke

McKenzie

Yu²,

Macko³

et al. 2008

JRRD

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“…Cellular changes in tissues of the paretic side may also negatively influence fitness, function, and cardiovascular disease (CVD) risk. Specifically, a deficit severity-dependent shift toward a fast-twitch muscle molecular phenotype in the paretic leg results in a more fatigable muscle fiber type that is more insulin resistant, which may contribute to the high incidence of IGT in this population [31][32][33]. Furthermore, nearly threefold elevated levels of tumor necrosis factor-α (TNF-α) messenger RNA are reported in hemiparetic quadriceps muscle from patients with stroke compared with those from nonparetic legs and nonstroke control subjects [34].…”

Section: Tissue-level Abnormalities After Strokementioning

confidence: 99%

Task-oriented treadmill exercise training in chronic hemiparetic stroke

Ivey

Hafer‐Macko²,

Macko³

2008

JRRD

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Abstract-Patients with stroke have elevated hemiparetic gait costs secondary to low activity levels and are often severely deconditioned. Decrements in peak aerobic capacity affect functional ability and cardiovascular-metabolic health and may be partially mediated by molecular changes in hemiparetic skeletal muscle. Conventional rehabilitation is time delimited in the subacute stroke phase and does not provide adequate aerobic intensity to reverse the profound detriments to fitness and function that result from stroke. Hence, we have studied progressive full body weight-support treadmill (TM) training as an adjunct therapy in the chronic stroke phase. Task-oriented TM training has produced measurable changes in fitness, function, and indices of cardiovascular-metabolic health after stroke, but the precise mechanisms for these changes remain under investigation. Further, the optimal dose of this therapy has yet to be identified for individuals with stroke and may vary as a function of deficit severity and outcome goals. This article summarizes the functional and metabolic decline caused by inactivity after stroke and provides current evidence that supports the use of TM training during the chronic stroke phase, with protocols and inclusion/exclusion criteria described. Our research findings are discussed in relation to associated research.Key words: aerobic activity, ambulatory function, cardiovascular disease risk, exercise training, hemiplegia, metabolic health, physical deconditioning, rehabilitation, stroke, treadmill. PROBLEM OF POSTSTROKE DECONDITIONINGStroke is a leading cause of disability [1][2][3][4], with residual neurological deficits that persistently impair function and lead to profound physical deconditioning [5][6]. By limiting mobility and increasing fall risk, the hemiparetic gait that accompanies chronic stroke promotes a sedentary lifestyle, which leads to disability through deconditioning and "learned non-use" [7][8]. Peak cardiovascular fitness levels following hemiparetic stroke are roughly half those of age-matched sedentary individuals [5,[9][10]. Further, the energy requirements of hemiparetic gait are elevated by 55 to 100 percent compared with age-matched control subjects [11][12]. This detrimental combination of poor peak exercise capacity and elevated energy demands for hemiparetic gait is termed diminished physiological fitness reserve [13]. The cardiovascular deconditioning coupled with the secondary body composition abnormalities that follow stroke Abbreviations: ACSM = American College of Sports Medicine, ADL = activities of daily living, BMI = body mass index, CVD = cardiovascular disease, ECG = electrocardiogram, HR = heart rate, HRR = HR reserve, IGT = impaired glucose tolerance, MHC = myosin heavy chain, T2DM = type 2 diabetes mellitus, TM = treadmill, TNF-α = tumor necrosis factor-α, WIQ = Walking Impairment Questionnaire, VA = Department of Veterans Affairs, VO 2 = peak oxygen consumption.

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“…A combination of mechanisms, including immobilization, disuse, inflammation, metabolic, and neurovegetative imbalance after stroke, results frequently in muscle wasting and may progress to the stroke‐related sarcopenia 1, 7. The presence of stroke‐specific sarcopenia has been proposed from experimental8 and clinical data 9, 10…”

Section: Introductionmentioning

confidence: 99%

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

Scherbakov

Knops

Ebner³

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

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BackgroundC‐terminal Agrin Fragment (CAF) has been proposed as a novel biomarker for sarcopenia originating from the degeneration of the neuromuscular junctions. In patients with stroke muscle wasting is a common observation that predicts functional outcome. We aimed to evaluate agrin sub‐fragment CAF22 as a marker of decreased muscle mass and physical performance in the early phase after acute stroke.MethodsPatients with acute ischaemic or haemorrhagic stroke (n = 123, mean age 70 ± 11 y, body mass index BMI 27.0 ± 4.9 kg/m2) admitted to inpatient rehabilitation were studied in comparison to 26 healthy controls of similar age and BMI. Functional assessments were performed at begin (23 ± 17 days post stroke) and at the end of the structured rehabilitation programme (49 ± 18 days post stroke) that included physical assessment, maximum hand grip strength, Rivermead motor assessment, and Barthel index. Body composition was assessed by bioelectrical impedance analysis (BIA). Serum levels of CAF22 were measured by ELISA.ResultsCAF22 levels were elevated in stroke patients at admission (134.3 ± 52.3 pM) and showed incomplete recovery until discharge (118.2 ± 42.7 pM) compared to healthy controls (95.7 ± 31.8 pM, p < 0.001). Simple regression analyses revealed an association between CAF22 levels and parameters of physical performance, hand grip strength, and phase angle, a BIA derived measure of the muscle cellular integrity. Improvement of the handgrip strength of the paretic arm during rehabilitation was independently related to the recovery of CAF22 serum levels only in those patients who showed increased lean mass during the rehabilitation.ConclusionsCAF22 serum profiles showed a dynamic elevation and recovery in the subacute phase after acute stroke. Further studies are needed to explore the potential of CAF22 as a serum marker to monitor the muscle status in patients after stroke.

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Muscle molecular phenotype after stroke is associated with gait speed

Cited by 96 publications

References 36 publications

Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke

Human genome comparison of paretic and nonparetic vastus lateralis muscle in patients with hemiparetic stroke

Task-oriented treadmill exercise training in chronic hemiparetic stroke

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation

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