Chronic exercise confers neuroprotection in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease that affects the CNS, resulting in accumulated loss of cognitive, sensory, and motor function. This study evaluates the neuropathological effects of voluntary exercise in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Two groups of C57BL/6J mice were injected with an emulsion containing myelin oligodendrocyte glycoprotein and then randomized to housing with a running wheel or a locked wheel. Exercising EAE mice exhibited a less severe neurological disease score and later onset of disease compared with sedentary EAE animals. Immune cell infiltration and demyelination in the ventral white matter tracts of the lumbar spinal cord were significantly reduced in the EAE exercise group compared with sedentary EAE animals. Neurofilament immunolabeling in the ventral pyramidal and extrapyramidal motor tracts displayed a more random distribution of axons and an apparent loss of smaller diameter axons, with a greater loss of fluorescence immunolabeling in the sedentary EAE animals. In lamina IX gray matter regions of the lumbar spinal cord, sedentary animals with EAE displayed a greater loss of α-motor neurons compared with EAE animals exposed to exercise. These findings provide evidence that voluntary exercise results in reduced and attenuated disability, reductions in autoimmune cell infiltration, and preservation of axons and motor neurons in the lumbar spinal cord of mice with EAE.

Repeatability of the timed 25-foot walk test for individuals with multiple sclerosis.

OBJECTIVE: The purpose of this study was to determine if there is a practice effect present in the timed 25-foot walk in ambulatory individuals with multiple sclerosis. DESIGN: Thirty six people (30 women and 6 men) diagnosed with relapsing remitting multiple sclerosis participated in two testing sessions, one week apart. Each participant performed two sequential trials of the timed 25-foot walk test per session and the walk performance was measured with a laser timing system. RESULTS: We observed improvements in walking speed between the two trials of session one (trial one: 6.42 (0.09) vs. trail two: 5.97 (0.08) seconds, p < 0.001). Within session two, performance remained stable (trial three: 5.71 (0.07) vs. trial four: 5.63 (0.07) seconds, p > 0.05). We also observed a significant improvement in walking speed when averages of the two trials were compared across sessions (session 1: 6.19 (0.09) vs. session 2: 5.67 (0.07) seconds, p < 0.01). CONCLUSIONS: Based on our results, familiarization of the timed 25-foot walk test improves stability of walk performance scores in ambulatory individuals with relapsing remitting multiple sclerosis.

Exercise and quality of life in women with multiple sclerosis.

The purpose of this study was to evaluate perceptions of quality of life after a 4-month progressive resistance training program for individuals with multiple sclerosis (MS). A second purpose was to examine participants' views about factors that facilitated or impeded exercise behavior. Qualitative interviews were conducted with eight females (Mage = 49.86, SD = 6.94) with relapsing remitting MS. Audio-tape recorded interviews were transcribed verbatim and coded. Walking performance improved (M = 13.08%, SD = 7.11). All participants perceived improvements in muscular strength and endurance while six indicated improvements in walking endurance and performance in tasks of daily living. Social benefits of participation were discussed by seven participants including interactions in the exercise environment. We concluded that supervised resistance training may promote improvements in QOL for women with relapsing remitting MS.

Cytokine responses to acute and chronic exercise in multiple sclerosis.

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.

Exercise and brain health--implications for multiple sclerosis: Part 1--neuronal growth factors.

The benefits of regular exercise to promote general health and reduce the risk of hypokinetic diseases associated with sedentary lifestyles are well recognized. Recent studies suggest that exercise may enhance neurobiological processes that promote brain health in aging and disease. A current frontier in the neurodegenerative disorder multiple sclerosis (MS) concerns the role of physical activity for promoting brain health through protective, regenerative and adaptive neural processes. Research on neuromodulation, raises the possibility that regular physical activity may mediate favourable changes in disease factors and symptoms associated with MS, in part through changes in neuroactive proteins. Insulin-like growth factor-I appears to act as a neuroprotective agent and studies indicate that exercise could promote this factor in MS. Neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor likely play roles in neuronal survival and activity-dependent plasticity. Physical activity has also been shown to up-regulate hippocampal BDNF, which may play a role in mood states, learning and memory to lessen the decline in cognitive function associated with MS. In addition, exercise may promote anti-oxidant defences and neurotrophic support that could attenuate CNS vulnerability to neuronal degeneration. Exercise exposure (preconditioning) may serve as a mechanism to enhance stress resistance and thereby may support neuronal survival under heightened stress conditions. Considering that axonal loss and cerebral atrophy occur early in the disease, exercise prescription in the acute stage could promote neuroprotection, neuroregeneration and neuroplasticity and reduce long-term disability. This review concludes with a proposed conceptual model to connect these promising links between exercise and brain health.

Exercise and brain health--implications for multiple sclerosis: Part II--immune factors and stress hormones.

Part I of this review addressed the possible modulatory role of exercise on neuronal growth factors to promote brain health in neurodegenerative diseases such as multiple sclerosis (MS), which is characterized by varied patterns of inflammation, demyelination and axonal loss. Part II presents evidence that supports the potential neuroprotective effect of exercise on the modulation of immune factors and stress hormones in MS. Many current therapies used to attenuate MS progression are mediated, at least in part, through alterations in the relative concentrations of pro- and anti-inflammatory cytokines. Exercise-induced alterations in local and systemic cytokine production may also benefit immune function in health and disease. Exercise immunomodulation appears to be mediated by a complex interaction of hormones, cytokines and neural factors that may favorably influence immune variables in MS. The promising interplay between exercise and brain health in MS deserves further investigation.

Ratings of perceived exertion during aerobic exercise in multiple sclerosis.

OBJECTIVE: To compare ratings of perceived exertion (RPEs) during aerobic exercise in people with multiple sclerosis (MS) and control participants. DESIGN: Prospective experimental study. SETTING: An exercise testing laboratory. PARTICIPANTS: Sedentary adults (n=12) with mild MS (Expanded Disability Status Scale score < or = 3) aged 30 to 45 years and sedentary age-matched and sex-matched controls (n=12). INTERVENTIONS: All participants underwent a graded aerobic exercise test on a cycle ergometer with breath-by-breath gas measurements and continuous heart rate monitoring. MAIN OUTCOME MEASURES: After completing the Modified Fatigue Impact Scale, participants rated their effort sense every 30 seconds during exercise using the modified Borg 10-point scale. RESULTS: The 2 study groups showed similar baseline characteristics except for higher fatigue scores in the MS group. There were no significant differences for any fitness measure, including oxygen cost slope (in VO(2) x min(-1) x W(-1)), VO(2), or work rate during exercise. Neither heart rate nor RPE--measured at 25%, 50%, 75%, and 100% of VO(2)peak--differed between groups. CONCLUSIONS: Despite greater reported fatigue levels, participants with MS showed similar RPE and physiologic responses to submaximal and maximal exercise compared with controls. In MS, the Borg 10-point scale may help improve evidence-based exercise prescriptions, which otherwise may be limited by fatigue, motor impairment, heat sensitivity, or autonomic dysfunction.

Early-phase neuroendocrine responses and strength adaptations following eccentric-enhanced resistance training.

The purpose of this study was to evaluate the early-phase muscular performance adaptations to 5 weeks of traditional (TRAD) and eccentric-enhanced (ECC+) progressive resistance training and to compare the acute postexercise total testosterone (TT), bioavailable testosterone (BT), growth hormone (GH), and lactate responses in TRAD- and ECC+-trained individuals. Twenty-two previously untrained men (22.1 +/- 0.8 years) completed 1 familiarization and 2 baseline bouts, 15 exercise bouts (i.e., 3 times per week for 5 weeks), and 2 postintervention testing bouts. Anthropometric and 1 repetition maximum (1RM) measurements (i.e., bench press and squat) were assessed during both baseline and postintervention testing. Following baseline testing, participants were randomized into TRAD (4 sets of 6 repetitions at 52.5% 1RM) or ECC+ (3 sets of 6 repetitions at 40% 1RM concentric and 100% 1RM eccentric) groups and completed the 5-week progressive resistance training protocols. During the final exercise bout, blood samples acquired at rest and following exercise were assessed for serum TT, BT, GH, and blood lactate. Both groups experienced similar increases in bench press (approximately 10%) and squat (approximately 22%) strength during the exercise intervention. At the conclusion of training, postexercise TT and BT concentrations increased (approximately 13% and 21%, respectively, p < 0.05) and GH concentrations increased (approximately 750-1200%, p < 0.05) acutely following exercise in both protocols. Postexercise lactate accumulation was similar between the TRAD (5.4 +/- 0.4) and ECC+ (5.6 +/- 0.4) groups; however, the ECC+ group's lactate concentrations were significantly lower than those of the TRAD group 30 to 60 minutes into recovery. In conclusion, TRAD training and ECC+ training appear to result in similar muscular strength adaptations and neuroendocrine responses, while postexercise lactate clearance is enhanced following ECC+ training.

Neuroendocrine responses to an acute bout of eccentric-enhanced resistance exercise.

PURPOSE: The purpose of this study was to compare the total testosterone (TT), bioavailable testosterone (BT), growth hormone (GH), lactate, and ratings of perceived exertion (RPE) responses between a single bout of traditional (TRAD) and eccentric-enhanced resistance exercise (ECC+) of matched training volumes. METHODS: Twenty-two previously untrained males (21.9+/-0.8 yr) completed one familiarization and one baseline 1RM testing bout, for the bench press and squat exercises, and then two exercise bouts. During exercise bout 1, all subjects completed a TRAD protocol (four sets of six reps at 52.5% 1RM), and the subsequent exercise bout consisted of either a TRAD or an ECC+ protocol (three sets of six reps at 40% 1RM concentric and 100% 1RM eccentric) for the bench press and squat exercises. Blood samples acquired at rest, immediately after (T1), and 15, 30, 45, and 60 min after exercise were assessed for serum TT, BT, GH, and blood lactate concentrations. RESULTS: Resting and postexercise TT, BT, and GH were not significantly different between groups. Postexercise TT was not elevated during either bout or in either group, whereas BT increased 15-16% at T1 in both groups during bout 2. Postexercise GH concentrations were elevated 500-7000% above baseline after both protocols. Postexercise lactate accumulation and RPE were greater with ECC+ than TRAD. CONCLUSION: TRAD and ECC+ show similar neuroendocrine and differing metabolic responses during the early phase of resistance exercise in untrained, college-age men.

Cardiovascular/non-insulin-dependent diabetes mellitus risk factors and intramyocellular lipid in healthy subjects: a sex comparison.

Little is known about the relationship between intramyocellular lipid (IMCL) and coronary artery disease (CAD)/non-insulin-dependent diabetes mellitus risk factors. The aim of the study was to examine the relationship between IMCL and CAD/non-insulin-dependent diabetes mellitus risk factors in healthy male (n = 9) and female (n = 10) subjects with similar norm-based aerobic fitness and body composition. Nineteen volunteers (21-36 years) completed health and physical activity questionnaires, cardiovascular and body composition evaluation, and assessment of thigh IMCL using proton magnetic resonance spectroscopy. Outcome measures were blood pressure, total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, interleukin 6, tumor necrosis factor alpha (TNF-alpha), homocysteine, insulin resistance (IR), percentage of body fat, waist-to-hip ratio, physical activity levels, and cardiovascular fitness. Analysis of variance was used for group comparisons. Correlation analyses were used to determine association between variables, and stepwise regression was used to determine predictive variables of IR. Women had 2-fold higher IMCL and greater IR than men (P < .05). Men had greater plasma homocysteine and interleukin 6 concentration (P < .05) as well as stronger correlations with CAD risk factors than female subjects. Correlation analyses using all subjects revealed a significant relationship between IMCL and waist-to-hip ratio, body weight, percentage of body fat, and IR. In the regression analysis, age, IMCL, and TNF-alpha were the strongest predictors of IR (R2 = 0.62, P < .01). Our results suggest that female subjects, matched for age and fitness, have higher IMCL compared with their male counterparts. IMCL was correlated with several CAD and prediabetes markers in both male and female subjects. In the final regression model, age, IMCL, and TNF-alpha were the strongest predictors of IR. Future studies with larger sample sizes are warranted.

Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients.

The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients. Myopathy, engendered by both heart failure and immunosuppression with glucocorticoids, is a post-transplant complication. The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability. We randomly assigned patients to either 6 months of resistance exercise (training group; n = 8) or a control (control group; n = 7) group. Exercise was initiated at 2 months after transplant. Biopsy of the right vastus lateralis was performed before and after the 6-month intervention. Myosin heavy chain (MHC) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemical assays were performed to determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity. There were no group differences (p >or=0.05) in MHC composition and enzymatic reserve at baseline. Improvements in the training group for citrate cynthase (+40%), 3-hydroxyacyl-CoA-dehydrogenase (+10%), and lactate dehydrogenase activity (+48%) were significantly greater (p

Intramyocellular lipid changes in men and women during aerobic exercise: a (1)H-magnetic resonance spectroscopy study.

This study was designed to compare intramyocellular lipid (IMCL) changes during 60 min of submaximal exercise in men and women. Eighteen moderately active (18-38 yr) men (n = 9) and women (n = 9) were recruited. Maximum oxygen consumption (O(2)max) and body composition were used to match subjects for aerobic fitness and body composition. Subjects performed cycle ergometry for 1 h at 65% of O(2)max. Expired gases were collected throughout exercise to determine caloric expenditure and substrate use. Blood samples were collected before and after exercise to evaluate markers of lipid metabolism. Pre- and postexercise proton spectra were acquired from the vastus lateralis using a 3-T whole-body imaging system. Spectra were acquired from an 18-mm(3) region of interest (echo time = 45 msec; repetition time = 2000 msec) for IMCL evaluation. IMCL decreased significantly with exercise (11.5-28.5% for men and 17.1-21.7% for women) (P < 0.05); however, there were no significant differences between men and women. Although changes were found for many plasma variables [free fatty acids, glycerol, and norepinephrine (P < 0.05)], group differences were only evident for norepinephrine. In conclusion, a significant decrease in IMCL was observed during 60 min of cycling in matched men and women.

Exercise and multiple sclerosis.

The pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor weakness, spasticity, poor balance, heat sensitivity and mental depression. Also, MS symptoms may lead to physical inactivity associated with the development of secondary diseases. Persons with MS are thus challenged by their disability when attempting to pursue an active lifestyle compatible with health-related fitness. Although exercise prescription is gaining favour as a therapeutic strategy to minimise the loss of functional capacity in chronic diseases, it remains under-utilised as an intervention strategy in the MS population. However, a growing number of studies indicate that exercise in patients with mild-to-moderate MS provides similar fitness and psychological benefits as it does in healthy controls. We reviewed numerous studies describing the responses of selected MS patients to acute and chronic exercise compared with healthy controls. All training studies reported positive outcomes that outweighed potential adverse effects of the exercise intervention. Based on our review, this article highlights the role of exercise prescription in the multidisciplinary approach to MS disease management for improving and maintaining functional capacity. Despite the often unpredictable clinical course of MS, exercise programmes designed to increase cardiorespiratory fitness, muscle strength and mobility provide benefits that enhance lifestyle activity and quality of life while reducing risk of secondary disorders. Recommendations for the evaluation of cardiorespiratory fitness, muscle performance and flexibility are presented as well as basic guidelines for individualised exercise testing and training in MS. Special considerations for exercise, including medical management concerns, programme modifications and supervision, in the MS population are discussed.

Effects of intermittent cycle exercise on intramyocellular lipid use and recovery.

The purpose of this investigation was to compare intramyocellular lipid (IMCL) changes in skeletal muscle in nine moderately trained subjects after 45 min of interval cycling and through 1 h of recovery. The exercise session was continuous with alternating cycling intensity achieving 50 (3 min) and 110% (2 min) of ventilatory threshold. Spectra from the vastus lateralis were acquired before, immediately after, and 60 min following exercise using a 1.5 T Signa whole-body magnet (point-resolved spectroscopy sequence, echo time 60 ms, transverse relaxation time 2000 ms, 128 acquisitions, and 20 mm3 voxel). Immediately following exercise, IMCL concentration decreased 38% compared to pre-exercise levels (P < 0.05). Fitness level and baseline IMCL were not correlated with changes in IMCL following exercise (P > 0.05). In the 60-min recovery, IMCL was reduced 30% compared to baseline (P < 0.05) and did not recover. In contrast, a nonexercising control group showed no change in IMCL. Our results suggest that IMCL decreased significantly following 45 min of interval cycling, with little recovery in the hour following.

Lower-limb performance disparities: implications for exercise prescription in multiple sclerosis.

The purpose of this study was to examine unilateral lower-limb exercise tolerance during fixed-load cycling to quantify performance disparities of the legs. Eight individuals with relapsing-remitting multiple sclerosis (MS) and seven controls performed submaximal single-leg cycling. Individuals with MS performed significantly more work with the stronger leg than the weaker leg (stronger leg: 6.4 +/- 1.7 kJ, weaker leg: 4.7 +/- 2.5 kJ, p = 0.02). The control group displayed no statistical differences between limbs (p = 0.36). These results highlight a need for individualized exercise testing when prescribing training programs for those with MS.

Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis.

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.

Bilateral differences in lower-limb performance in individuals with multiple sclerosis.

Bilateral differences in lower-limb strength in people with multiple sclerosis (MS) have been clinically observed. The objectives of this study were to quantify bilateral differences in lower-limb performance and metabolism during exercise. Eight ambulatory individuals with mild MS with an Expanded Disability Status Scale score of 2.6 +/- 1.6 and seven non-MS controls completed bilateral assessments of muscle strength and incremental cycling. Individuals with MS had significant (p < 0.05) between-leg differences in leg strength (strong leg: 43.3 +/- 12.7 kg vs weak leg: 37.7 +/- 15.2 kg), peak oxygen uptake (strong leg: 13.7 +/- 3.2 mL/kg/min vs weak leg: 10.6 +/- 3.0 mL/kg/min), and peak workload (strong leg: 73.4 +/- 22.3 W vs weak leg: 56.3 +/- 26.2 W). No between-leg differences were found in controls (p > 0.05). As anticipated, individuals with MS exhibited significantly greater asymmetry for strength, oxygen uptake, and workload than controls (p < 0.05). The differences between legs varied from 2% to 30% for maximal strength and 4% to 66% for cycling workload in the MS group and 4% to 24% and 0% to 8% for the control group, respectively. Preliminary evidence suggests that the magnitude of differences may be related to limitations in aerobic function.

Asymmetrical hip bone density in multiple sclerosis.

As multiple sclerosis (MS) may affect one leg more than the other, we predicted that bone mineral density (BMD) would be lower in the limb self-identified as more affected. Therefore, the purpose of this study was to determine whether ambulatory individuals with MS displaying moderate-to-severe lower-extremity paresis exhibit asymmetrical femoral neck BMD. Dual-energy x-ray absorptiometry was used to assess proximal femoral neck BMD. Lower BMD was observed in the proximal femoral neck of the more paretic limb (P = .001) in a group (N = 23) of ambulatory individuals with relapsing-remitting MS (RRMS). Our preliminary findings suggest that bilateral hip screening may be important in the early detection of compromised bone health in ambulatory individuals with RRMS. Further research is warranted to fully characterize the factors and mechanisms associated with bone loss and identify effective strategies for optimizing bone health in people with MS.

Training augments resistance exercise induced elevation of circulating brain derived neurotrophic factor (BDNF).

Brain derived neurotrophic factor (BDNF) is postulated to be an important mediator of exercise-induced neuroprotection. We tested the hypothesis that resistance exercise elevates circulating BDNF. Twenty healthy untrained college-aged males underwent a 5-week traditional or eccentric-enhanced progressive resistance training intervention. Blood was acquired at rest and 1, 30, and 60min following a standardized resistance exercise testing bout performed at baseline and at the completion of the intervention. Serum BDNF responses did not differ between the two groups at any time point during baseline or post-intervention testing; thus, all values were combined into a single cohort for further analysis. Resting BDNF was not altered by the exercise training intervention [23,304+/-1835pg/ml (baseline) vs. 19,433+/-1992pg/ml (post-intervention)]. Following the baseline resistance exercise bout, serum BDNF increased 32% (p<0.05) and was gradually reduced to 41% below resting levels at 60min into recovery (p<0.01). During post-intervention testing, serum BDNF increased 77% in response to the standardized resistance exercise bout (p<0.01) and returned to resting values within 30min. Ultimately, the change in serum BDNF from rest to immediately post-exercise was 98% greater at post-intervention than at baseline (p<0.05). Our study is the first to demonstrate that resistance exercise induces a robust, yet transient, elevation of circulating BDNF and that progressive resistance training augments this response; perhaps demonstrating one mechanism through which exercise influences brain health.