Randomization to Treadmill Training Improves Physical and Metabolic Health in Association With Declines in Oxidative Stress in Stroke

  • Monica C. Serra
    Corresponding author Monica Serra, PhD, Division of Geriatrics, Gerontology & Palliative Medicine, UT Health San Antonio, 7400 Merton Minter (182-GRECC), San Antonio, TX 78229.
    Division of Geriatrics, Gerontology & Palliative Medicine and the Sam & Ann Barshop Institute for Longevity & Aging Studies, Department of Medicine, UT Health San Antonio, San Antonio, TX

    San Antonio Geriatric Research, Education, and Clinical Center (GRECC), South Texas Veterans Health Care System, San Antonio, TX
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  • Charlene E. Hafer-Macko
    Department of Neurology, University of Maryland School of Medicine, Baltimore, MD

    Department of Pharmacology, UT Health San Antonio, San Antonio, TX
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  • Ronna Robbins
    San Antonio Geriatric Research, Education, and Clinical Center (GRECC), South Texas Veterans Health Care System, San Antonio, TX
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  • Jason C. O'Connor
    Department of Pharmacology, UT Health San Antonio, San Antonio, TX
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  • Alice S. Ryan
    Baltimore GRECC, VA Maryland Health Care System, Baltimore, MD

    Division of Geriatrics and Palliative Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
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      To investigate the effect of aerobic exercise vs control (stretching/balance) on inflammatory and oxidative stress biomarkers in stroke survivors and whether these changes are associated with improvements in physical and metabolic health.


      Randomized controlled trial.


      The general communities of Baltimore, Maryland, and Atlanta, Georgia.


      Two hundred forty-six older (>50 years), chronic (>6 months) survivors of stroke (N=246) with hemiparetic gait were recruited, with 51 completing pre-intervention testing and 39 completing postintervention testing. Participants were required to have completed all conventional physical therapy and be capable of walking 3 minutes on a treadmill (N=246).


      Participants completed 6 months of 2 times/wk stretching or balance (ST; n=19) or 3 times/wk aerobic treadmill rehabilitation (TM; n=20;).

      Main Outcome Measure(s)

      Peak oxygen uptake rate (V̇o2peak), 6-minute walking distance (6MWD), fasting plasma glucose, insulin, oxidative stress, and inflammatory biomarkers were assessed pre- and postintervention. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated.


      Physical function and metabolic health parameters tended to improve after TM but not ST (ST vs TM: V̇o2peak: −9% vs 24%, P<.01; 6MWD: 1% vs 15%, P=.05; insulin: −1% vs −31%, P=.05; HOMA-IR: −3% vs −29%, P=.06). Plasma concentrations of nitrotyrosine, protein carbonyls, and oxidized low-density lipoprotein (oxLDL) tended to decrease from pre-intervention concentrations in response to TM compared to ST (ST vs TM: nitrotyrosine: 2% vs −28%, P=.01; protein carbonyls: −4% vs −34%, P=.08; oxLDL: −3% vs −32%, P<.01). Changes in circulating concentrations of C-reactive protein, protein carbonyls, and oxLDL were negatively associated with changes in V̇o2peak and 6MWD (r's=−0.40 to −0.76) and positively associated with fasting plasma insulin and HOMA-IR (r's=0.52-0.81, Ps<.01).


      Six months of TM tends to be associated with increased functional capacity and reduced oxidative stress in chronic stroke survivors. Our findings identify potentially modifiable systemic markers of inflammation and oxidative stress important to stroke rehabilitation and provide potential targets for novel therapeutics in future studies.


      List of abbreviations:

      6MWD (6-minute walk distance), BBS (Berg Balance Scale), BMI (body mass index), CVD (cardiovascular disease), DGI (Dynamic Gait Index), FSS (Fatigue Severity Scale), HNE (hydroxynonenal adducts), HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), HRR (heart rate reserve), hs-CRP (high-sensitivity C-reactive protein), IL-6 (intereukin-6), MDA (nitrotyrosine, protein carbonyls, malondialdehyde adducts), oxLDL (oxidized low-density lipoprotein), RD (registered dietitian), ST (6 months of stretching/balance), T2DM (type 2 diabetes mellitus), TM (6 months of aerobic treadmill rehabilitation), TUG (Timed Up and Go test), VA (Veterans Affairs), V̇o2 (volume of oxygen)
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