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Key Words
- Musculoskeletal magnetic resonance (imaging and spectroscopy)

Current Research Interest and projects


- “Association Française Contre les Myopathies” Grant 2002-2005 Comparative analysis of metabolic and electromyographic indices of muscle fatigue in children and adults Role: PI
- Biocodex Laboratories Grant 1999-2006 Metabolic basis of pathological and physiological fatigue Role: PI
- Amaury Sport Organisation Grant 2002-2005 Metabolic changes resulting from intense physical training Role: PI
- CNRS Grant 2004-2006 Eccentric exercise : Beneficial and detrimental effects Role: PI
- CNRS Grant 2004-2008 Functional investigations of muscle fatigue using 31P MRS and MRI Role: PI
- CNRS Grant 2004-2008 Metabolic control of muscle energy production : A combined investigation using 31P MRS, MRI, surface electromyography and near infrared spectroscopy Role: PI


- “Association Française Contre les Myopathies” Grant 1998-2000 Muscle energetics in inflammatory diseases. Role: Co-Investigator
- “Association Française Contre les Myopathies” Grant 1998-2002 Muscle energetics in Malignant Hyperthermias Role: Co-Investigator
- “Association Française Contre les Myopathies” Grant 1998-2002 Combined investigations of muscle function using MR and EMG techniques Role: Co-Investigator
- “Association Française Contre les Myopathies” Grant 2000-2002 Anatomical and metabolic charaterization of Charcot-Marie-Tooth disease in a transgenic mouse model by microimaging and spectroscopy Role: Co-Investigator
- CNRS Grant 1999-2002 Metabolic aspects of muscle fatigue in rat gastrocnemius muscle Role: Co-Investigator
- CNRS Grant 1999-2002 Alterations of muscle energetics in human muscle diseases : A non invasive investigation Role: PI



Journal Article

  • Chatel, B, Messonnier, LA, Barge, Q, Vilmen, C, Noirez, P, Bernard, M, Pialoux, V & Bendahan, D 2018, “Endurance training reduces exercise-induced acidosis and improves muscle function in a mouse model of sickle cell disease”, Molecular Genetics and Metabolism, vol. 123, no. 3, p. 400-410.
    Résumé : Sickle cell disease (SCD) mice (Townes model of SCD) presented exacerbated exercise-induced acidosis and fatigability as compared to control animals. We hypothesize that endurance training could represent a valuable approach to reverse these muscle defects. Endurance-trained HbAA (HbAA-END, n=10), HbAS (HbAS-END, n=11) and HbSS (HbSS-END, n=8) mice were compared to their sedentary counterparts (10 HbAA-SED, 10 HbAS-SED and 9 HbSS-SED mice) during two rest - exercise - recovery protocols during which muscle energetics and function were measured. In vitro analyses of some proteins involved in muscle energetics, pH regulation and oxidative stress were also performed. Exercise-induced acidosis was lower in HbSS-END mice as compared to their sedentary counterparts during both moderate (p<0.001) and intense (p<0.1) protocols. The total force production measured during both protocols was higher in trained mice compared to sedentary animals. In vitro analyses revealed that enolase/citrate synthase ratio was reduced in HbSS-END (p<0.001) and HbAS-END (p<0.01) mice compared to their sedentary counterparts. In addition, malondialdehyde concentration was reduced in trained mice (p<0.05). In conclusion, endurance training would reverse the more pronounced exercise-induced acidosis, reduce oxidative stress and ameliorate some of the muscle function parameters in SCD mice.
    Mots-clés : crmbm, msk, Muscle energetics, Muscle force production, pH, Physical activity.

  • Fouré, A, Ogier, AC, Le Troter, A, Vilmen, C, Feiweier, T, Guye, M, Gondin, J, Besson, P & Bendahan, D 2018, “Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography: Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability”, Radiology, vol. 287, no. 2, p. 592-607.
    Résumé : Purpose To demonstrate the reproducibility of the diffusion properties and three-dimensional structural organization measurements of the lower leg muscles by using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0-T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On the basis of robust statistical mapping analyses, this study also aimed at determining the sensitivity of the measurements to sex difference and intramuscular variability. Materials and Methods All examinations were performed with ethical review board approval; written informed consent was obtained from all volunteers. Reproducibility of diffusion tensor indexes assessment including eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle volume and architecture (ie, fiber length and pennation angle) were characterized in lower leg muscles (n = 8). Intramuscular variability and sex differences were characterized in young healthy men and women (n = 10 in each group). Student t test, statistical parametric mapping, correlation coefficients (Spearman rho and Pearson product-moment) and coefficient of variation (CV) were used for statistical data analysis. Results High reproducibility of measurements (mean CV ± standard deviation, 4.6% ± 3.8) was determined in diffusion properties and architectural parameters. Significant sex differences were detected in FA (4.2% in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for the entire lower leg; P = .008), whereas architecture parameters were almost identical across sex. Additional differences were found independently of sex in diffusion properties and architecture along several muscles of the lower leg. Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows a reproducible assessment of structural organization of superficial and deep muscles, giving indirect information on muscle function. ©RSNA, 2018 Online supplemental material is available for this article.
    Mots-clés : crmbm, msk.

  • Macia, M, Pecchi, E, Desrois, M, Lan, C, Vilmen, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2018, “Exercise training impacts exercise tolerance and bioenergetics in gastrocnemius muscle of non-obese type-2 diabetic Goto-Kakizaki rat in vivo”, Biochimie.
    Résumé : The functional and bioenergetics impact of regular physical activity upon type-2 diabetic skeletal muscle independently of confounding factors of overweight remains undocumented. Here, gastrocnemius muscle energy fluxes, mitochondrial capacity and mechanical performance were assessed noninvasively and longitudinally in non-obese diabetic Goto-Kakizaki rats using magnetic resonance (MR) imaging and dynamic 31-phosphorus MR spectroscopy (31P-MRS) throughout a 6-min fatiguing bout of exercise performed before, in the middle (4-week) and at the end of an 8-week training protocol consisting in 60-min daily run on a treadmill. The training protocol reduced plasmatic insulin level (-61%) whereas blood glucose and non-esterified fatty acids levels remained unaffected, thereby indicating an improvement of insulin sensitivity. It also increased muscle mitochondrial citrate synthase activity (+45%) but this increase did not enhance oxidative ATP synthesis capacity in working muscle in vivo while glycolytic ATP production was increased (+33%). On the other hand, the training protocol impaired maximal force-generating capacity (-9%), total amount of force produced (-12%) and increased ATP cost of contraction (+32%) during the fatiguing exercise. Importantly, these deleterious effects were transiently worsened in the middle of the 8-week period, in association with reduced oxidative capacity and increased basal [Pi]/[PCr] ratio (an in vivo biomarker of muscle damage). These data demonstrate that the beneficial effect of regular training on insulin sensitivity in non-obese diabetic rat occurs separately from any improvement in muscle mitochondrial function and might be linked to an increased capacity for metabolizing glucose through anaerobic process in exercising muscle.
    Mots-clés : crmbm, cvs, Diabetes, Mitochondrial capacity, msk, Nuclear magnetic resonance, Regular physical activity, Skeletal muscle function.


Journal Article

  • Chatel, B, Hourdé, C, Gondin, J, Fouré, A, Le Fur, Y, Vilmen, C, Bernard, M, Messonnier, LA & Bendahan, D 2017, “Impaired muscle force production and higher fatigability in a mouse model of sickle cell disease”, Blood Cells, Molecules & Diseases, vol. 63, p. 37-44.
    Résumé : Skeletal muscle function has been scarcely investigated in sickle cell disease (SCD) so that the corresponding impact of sickle hemoglobin is still a matter of debate. The purpose of this study was to investigate muscle force production and fatigability in SCD and to identify whether exercise intensity could have a modulatory effect. Ten homozygous sickle cell (HbSS), ten control (HbAA) and ten heterozygous (HbAS) mice were submitted to two stimulation protocols (moderate and intense) to assess force production and fatigability. We showed that specific maximal tetanic force was lower in HbSS mice as compared to other groups. At the onset of the stimulation period, peak force was reduced in HbSS and HbAS mice as compared to HbAA mice. Contrary to the moderate protocol, the intense stimulation protocol was associated with a larger decrease in peak force and rate of force development in HbSS mice as compared to HbAA and HbAS mice. These findings provide in vivo evidence of impaired muscle force production and resistance to fatigue in SCD. These changes are independent of muscle mass. Moreover, SCD is associated with muscle fatigability when exercise intensity is high.
    Mots-clés : crmbm, Exercise intensity, msk, Muscle mass, Muscle volume, Rate of force development.

  • Chatel, B, Messonnier, LA & Bendahan, D 2017, “Exacerbated in vivo metabolic changes suggestive of a spontaneous muscular vaso-occlusive crisis in exercising muscle of a sickle cell mouse”, Blood Cells, Molecules, and Diseases, vol. 65, p. 56-59, viewed 18August,2017, .
    Résumé : While sickle cell disease (SCD) is characterized by frequent vaso-occlusive crisis (VOC), no direct observation of such an event in skeletal muscle has been performed in vivo. The present study reported exacerbated in vivo metabolic changes suggestive of a spontaneous muscular VOC in exercising muscle of a sickle cell mouse. Using magnetic resonance spectroscopy of phosphorus 31, phosphocreatine and inorganic phosphate concentrations and intramuscular pH were measured throughout two standardized protocols of rest – exercise – recovery at two different intensities in ten SCD mice. Among these mice, one single mouse presented divergent responses. A statistical analysis (based on confidence intervals) revealed that this single mouse presented slower phosphocreatine resynthesis and inorganic phosphate disappearance during the post-stimulation recovery of one of the protocols, what could suggest an ischemia. This study described, for the first time in a sickle cell mouse in vivo, exacerbated metabolic changes triggered by an exercise session that would be suggestive of a live observation of a muscular VOC. However, no evidence of a direct cause-effect relationship between exercise and VOC has been put forth.
    Mots-clés : crmbm, HbS polymerization, Magnetic resonance spectroscopy of phosphorus 31, msk, Physical activity, Red blood cell sickling.

  • Fatehi, F, Salort-Campana, E, Le Troter, A, Lareau-Trudel, E, Bydder, M, Fouré, A, Guye, M, Bendahan, D & Attarian, S 2017, “Long-term follow-up of MRI changes in thigh muscles of patients with Facioscapulohumeral dystrophy: A quantitative study”, PloS One, vol. 12, no. 8, p. e0183825.
    Résumé : Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common hereditary muscular disorders. Currently FSHD has no known effective treatment and detailed data on the natural history are lacking. Determination of the efficacy of a given therapeutic approach might be difficult in FSHD given the slow and highly variable disease progression. Magnetic resonance imaging (MRI) has been widely used to qualitatively and quantitatively evaluate in vivo the muscle alterations in various neuromuscular disorders. The main aim of the present study was to investigate longitudinally the time-dependent changes occurring in thigh muscles of FSHD patients using quantitative MRI and to assess the potential relationships with the clinical findings. Thirty-five FSHD1 patients (17 females) were enrolled. Clinical assessment tools including manual muscle testing using medical research council score (MRC), and motor function measure (MFM) were recorded each year for a period ranging from 1 to 2 years. For the MRI measurements, we used a new quantitative index, i.e., the mean pixel intensity (MPI) calculated from the pixel-intensity distribution in T1 weighted images. The corresponding MPI scores were calculated for each thigh, for each compartment and for both thighs totally (MPItotal). The total mean pixel intensity (MPItotal) refers to the sum of each pixel signal intensity divided by the corresponding number of pixels. An increased MPItotal indicates both a raised fat infiltration together with a reduced muscle volume thereby illustrating disease progression. Clinical scores did not change significantly over time whereas MPItotal increased significantly from an initial averaged value of 39.6 to 41.1 with a corresponding rate of 0.62/year. While clinical scores and MPItotal measured at the start of the study were significantly related, no correlation was found between the rate of MPItotal and MRC sum score changes, MFMtotal and MFM subscores. The relative rate of MPItotal change was 2.3% (0.5-4.3)/year and was significantly higher than the corresponding rates measured for MRCS 0% (0-1.7) /year and MFMtotal 0% (0-2.0) /year (p = 0.000). On the basis of these results, we suggested that muscle MRI and more particularly the MPItotal index could be used as a reliable biomarker and outcome measure of disease progression. In slowly progressive myopathies such as FSHD, the MPItotal index might reveal subclinical changes, which could not be evidenced using clinical scales over a short period of time.
    Mots-clés : crmbm, Humans, Magnetic Resonance Imaging, msk, Muscle, Skeletal, Muscular Dystrophy, Facioscapulohumeral.

  • Fouré, A & Bendahan, D 2017, “Is Branched-Chain Amino Acids Supplementation an Efficient Nutritional Strategy to Alleviate Skeletal Muscle Damage? A Systematic Review”, Nutrients, vol. 9, no. 10.
    Résumé : Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually consumed as nutritional supplements by many athletes and people involved in regular and moderate physical activities regardless of their practice level. BCAAs have been initially shown to increase muscle mass and have also been implicated in the limitation of structural and metabolic alterations associated with exercise damage. This systematic review provides a comprehensive analysis of the literature regarding the beneficial effects of BCAAs supplementation within the context of exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation was also analyzed according to the supplementation strategy-amount of BCAAs, frequency and duration of the supplementation-and the extent of muscle damage. The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42017073006) and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Literature search was performed from the date of commencement until August 2017 using four online databases (Medline, Cochrane library, Web of science and ScienceDirect). Original research articles: (i) written in English; (ii) describing experiments performed in Humans who received at least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a nutritional strategy and (iii) reporting a follow-up of at least one day after exercise-induced muscle damage, were included in the systematic review analysis. Quality assessment was undertaken independently using the Quality Criteria Checklist for Primary Research. Changes in indirect markers of muscle damage were considered as primary outcome measures. Secondary outcome measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were included in the analysis. A high heterogeneity was found regarding the different outcomes of these studies. The risk of bias was moderate considering the quality ratings were positive for six and neutral for three. Although a small number of studies were included, BCAAs supplementation can be efficacious on outcomes of exercise-induced muscle damage, as long as the extent of muscle damage was low-to-moderate, the supplementation strategy combined a high daily BCAAs intake (>200 mg kg-1 day-1) for a long period of time (>10 days); it was especially effective if taken prior to the damaging exercise.
    Mots-clés : branched-chain amino acids (BCAAs), crmbm, exercise-induced muscle damage, msk, nutritional strategy, skeletal muscle.

  • Fouré, A, Duhamel, G, Vilmen, C, Bendahan, D, Jubeau, M & Gondin, J 2017, “Fast measurement of the quadriceps femoris muscle transverse relaxation time at high magnetic field using segmented echo-planar imaging”, Journal of magnetic resonance imaging: JMRI, vol. 45, no. 2, p. 356-368.
    Résumé : PURPOSE: To assess and validate a technique for transverse relaxation time (T2 ) measurements of resting and recovering skeletal muscle following exercise with a high temporal resolution and large volume coverage using segmented spin-echo echo-planar imaging (sSE-EPI). MATERIALS AND METHODS: Experiments were performed on a 3T magnetic resonance imaging (MRI) scanner using a multislice sSE-EPI technique applied at different echo times (TEs). T2 measurements were first validated in vitro in calibrated T2 phantoms (range: 25-152 ms) by comparing sSE-EPI, standard spin-echo (SE), and multislice multiecho (MSME) techniques (using a fitting procedure or a 2-TEs calculation). In vivo measurements of resting T2 quadriceps femoris (QF) muscle were performed with both sSE-EPI and MSME sequences. Finally, sSE-EPI was used to quantify T2 changes in recovering muscle after an exercise. RESULTS: T2 values measured in vitro with sSE-EPI were similar to those assessed with SE (P > 0.05). In vitro and in vivo T2 measurements obtained with sSE-EPI were independent of the T2 determination procedure (P > 0.05). In contrast, both in vitro and in vivo T2 values derived from MSME were significantly different when using 2-TEs calculation as compared to the fitting procedure (P < 0.05). sSE-EPI allowed the detection of increased T2 values in the QF muscle immediately after exercise (+14 ± 9%), while lower T2 values were recorded less than 2 min afterwards (P < 0.05). CONCLUSION: sSE-EPI sequence is a relevant method to monitor exercise-induced T2 changes of skeletal muscles over large volume coverage and to detect abnormal patterns of muscle activation. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:356-368.
    Mots-clés : crmbm, Exercise, MRI, msk, skeletal muscle, spin-echo sequence, T2.

  • Guenoun, D, Fouré, A, Pithioux, M, Guis, S, Le Corroller, T, Mattei, J-P, Pauly, V, Guye, M, Bernard, M, Chabrand, P, Champsaur, P & Bendahan, D 2017, “Correlative Analysis of Vertebral Trabecular Bone Microarchitecture and Mechanical Properties: A Combined Ultra-high Field (7 Tesla) MRI and Biomechanical Investigation”, Spine, vol. 42, no. 20, p. E1165-E1172.
    Résumé : STUDY DESIGN: High-resolution imaging and biomechanical investigation of ex-vivo vertebrae. OBJECTIVE: The aim of this study was to assess bone microarchitecture of cadaveric vertebrae using ultra-high field (UHF) 7 Tesla magnetic resonance imaging (MRI) and to determine whether the corresponding microarchitecture parameters were related to bone mineral density (BMD) and bone strength assessed by dual-energy x-ray absorptiometry (DXA) and mechanical compression tests. SUMMARY OF BACKGROUND DATA: Limitations of DXA for the assessment of bone fragility and osteoporosis have been recognized and criteria of microarchitecture alteration have been included in the definition of osteoporosis. Although vertebral fracture is the most common osteoporotic fracture, no study has assessed directly vertebral trabecular bone microarchitecture. METHODS: BMD of 24 vertebrae (L2, L3, L4) from eight cadavers was investigated using DXA. The bone volume fraction (BVF), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) of each vertebra were quantified using UHF MRI. Measurements were performed by two operators to characterize the inter-rater reliability. The whole set of specimens underwent mechanical compression tests to failure and the corresponding failure stress was calculated. RESULTS: The inter-rater reliability for bone microarchitecture parameters was good with intraclass correlation coefficients ranging from 0.82 to 0.94. Failure load and stress were significantly correlated with BVF, Tb.Sp, and BMD (P < 0.05). Tb.Th was only correlated with the failure stress (P < 0.05). Multiple regression analysis demonstrated that the combination of BVF and BMD improved the prediction of the failure stress from an adjusted R = 0.384 for BMD alone to an adjusted R = 0.414. CONCLUSION: We demonstrated for the first time that the vertebral bone microarchitecture assessed with UHF MRI was significantly correlated with biomechanical parameters. Our data suggest that the multimodal assessment of BMD and trabecular bone microarchitecture with UHF MRI provides additional information on the risk of vertebral bone fracture and might be of interest for the future investigation of selected osteoporotic patients. LEVEL OF EVIDENCE: N /A.
    Mots-clés : crmbm, msk.

  • Ogier, A, Sdika, M, Foure, A, Le Troter, A & Bendahan, D 2017, “Individual muscle segmentation in MR images: A 3D propagation through 2D non-linear registration approaches”, Conference proceedings: .. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, vol. 2017, p. 317-320.
    Résumé : Manual and automated segmentation of individual muscles in magnetic resonance images have been recognized as challenging given the high variability of shapes between muscles and subjects and the discontinuity or lack of visible boundaries between muscles. In the present study, we proposed an original algorithm allowing a semi-automatic transversal propagation of manually-drawn masks. Our strategy was based on several ascending and descending non-linear registration approaches which is similar to the estimation of a Lagrangian trajectory applied to manual masks. Using several manually-segmented slices, we have evaluated our algorithm on the four muscles of the quadriceps femoris group. We mainly showed that our 3D propagated segmentation was very accurate with an averaged Dice similarity coefficient value higher than 0.91 for the minimal manual input of only two manually-segmented slices.
    Mots-clés : crmbm, msk.

  • Wegrzyk, J, Ranjeva, J-P, Fouré, A, Kavounoudias, A, Vilmen, C, Mattei, J-P, Guye, M, Maffiuletti, NA, Place, N, Bendahan, D & Gondin, J 2017, “Specific brain activation patterns associated with two neuromuscular electrical stimulation protocols”, Scientific Reports, vol. 7, no. 1, p. 2742.
    Résumé : The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements.
    Mots-clés : crmbm, msk.


Journal Article

  • Béchir, N, Pecchi, E, Vilmen, C, Le Fur, Y, Amthor, H, Bernard, M, Bendahan, D & Giannesini, B 2016, “ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo”, FASEB journal: official publication of the Federation of American Societies for Experimental Biology, vol. 30, no. 10, p. 3551-3562.
    Résumé : Postnatal blockade of the activin type IIB receptor (ActRIIB) represents a promising therapeutic strategy for counteracting dystrophic muscle wasting. However, its impact on muscle function and bioenergetics remains poorly documented in physiologic conditions. We have investigated totally noninvasively the effect of 8-wk administration of either soluble ActRIIB signaling inhibitor (sActRIIB-Fc) or vehicle PBS (control) on gastrocnemius muscle force-generating capacity, energy metabolism, and anatomy in dystrophic mdx mice using magnetic resonance (MR) imaging and dynamic [(31)P]-MR spectroscopy ([(31)P]-MRS) in vivo ActRIIB inhibition increased muscle volume (+33%) without changing fiber-type distribution, and increased basal animal oxygen consumption (+22%) and energy expenditure (+23%). During an in vivo standardized fatiguing exercise, maximum and total absolute contractile forces were larger (+40 and 24%, respectively) in sActRIIB-Fc treated animals, whereas specific force-generating capacity and fatigue resistance remained unaffected. Furthermore, sActRIIB-Fc administration did not alter metabolic fluxes, ATP homeostasis, or contractile efficiency during the fatiguing bout of exercise, although it dramatically reduced the intrinsic mitochondrial capacity for producing ATP. Overall, sActRIIB-Fc treatment increased muscle mass and strength without altering the fundamental weakness characteristic of dystrophic mdx muscle. These data support the clinical interest of ActRIIB blockade for reversing dystrophic muscle wasting.-Béchir, N., Pecchi, E., Vilmen, C., Le Fur, Y., Amthor, H., Bernard, M., Bendahan, D., Giannesini, B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo.
    Mots-clés : crmbm, Duchenne muscular dystrophy, msk, Muscle Fatigue, myostatin inhibition, skeletal muscle hypertrophy.

  • Fatehi, F, Salort-Campana, E, Le Troter, A, Bendahan, D & Attarian, S 2016, “Muscle MRI of facioscapulohumeral dystrophy (FSHD): A growing demand and a promising approach”, Revue Neurologique, vol. 172, no. 10, p. 566-571.
    Résumé : Facioscapulohumeral muscular dystrophy (FSHD), an inherited and progressive muscle disorder, is among the most common hereditary muscle disorders. From a clinical vantage point, FSHD is characterized by weakness of the facial, shoulder (often with scapular winging), arm (including biceps and triceps) and abdominal muscles. Forearm muscles are usually spared and weakness is usually asymmetrical. Over the past few decades, muscle magnetic resonance imaging (MRI) has become established as a reliable and accurate noninvasive tool for the diagnosis and assessment of progression in neuromuscular diseases, showing specific patterns of muscle involvement for a number of myopathies. More recently, MRI has been used to noninvasively identify quantitative biomarkers, allowing evaluation of the natural progression of disease and assessment of therapeutic interventions. In the present review, the intention was to present the most significant MRI developments related to diagnosis and pattern recognition in FSHD and to discuss its capacity to provide outcome measures.
    Mots-clés : crmbm, Facioscapulohumeral dystrophy, FSHD, Measurement, MRI, msk, Pattern recognition.

  • Fouré, A, Nosaka, K, Gastaldi, M, Mattei, J-P, Boudinet, H, Guye, M, Vilmen, C, Le Fur, Y, Bendahan, D & Gondin, J 2016, “Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial”, Clinical Nutrition (Edinburgh, Scotland), vol. 35, no. 1, p. 83-94.
    Résumé : BACKGROUND & AIMS: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. METHODS: (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. RESULTS: No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). CONCLUSIONS: The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage.
    Mots-clés : crmbm, Double blind randomized placebo controlled trial, Exercise induced-muscle damage, Magnetic Resonance Spectroscopy, msk.

  • Layec, G, Bringard, A, LE Fur, Y, Micallef, J-P, Vilmen, C, Perrey, S, Cozzone, PJ & Bendahan, D 2016, “Mitochondrial Coupling and Contractile Efficiency in Humans with High and Low V˙O2peaks”, Medicine and Science in Sports and Exercise, vol. 48, no. 5, p. 811-821.
    Résumé : INTRODUCTION: Endurance training elicits tremendous adaptations of the mitochondrial energetic capacity. Yet, the effects of training or physical fitness on mitochondrial efficiency during exercise are still unclear. Accordingly, the purpose of the present study was to examine in vivo the differences in mitochondrial efficiency and ATP cost of contraction during exercise in two groups of adults differing in their aerobic capacity. METHOD: We simultaneously assessed the ATP synthesis and O2 fluxes with P-magnetic resonance spectroscopy and pulmonary gas exchange measurements in seven endurance-trained (ET, V˙O2max: 67 ± 8 mL·min·kg) and seven recreationally active (RA, V˙O2max: 43 ± 7 mL·min·kg) subjects during 6 min of dynamic moderate-intensity knee extension. RESULTS: The ATP cost of dynamic contraction was not significantly different between ET and RA (P > 0.05). Similarly, end-exercise O2 consumption was not significantly different between groups (ET: 848 ± 155 mL·min and RA: 760 ± 131 mL·min, P > 0.05). During the recovery period, the PCr offset time constant was significantly faster in ET compared with RA (ET: 32 ± 8 s and RA: 43 ± 10 s, P < 0.05), thus indicating an increased mitochondrial capacity for ATP synthesis in the quadriceps of ET. In contrast, the estimated mitochondrial efficiency during exercise was not significantly different (P/O, ET: 2.0 ± 1.0 and RA: 1.8 ± 0.4, P > 0.05). Consequently, the higher mitochondrial capacity for ATP synthesis in ET likely originated from an elevated mitochondrial volume density, mitochondria-specific respiratory capacity, and/or slower postexercise inactivation of oxidative phosphorylation by the parallel activation mechanism. CONCLUSION: Together, these findings reveal that 1) mitochondrial and contractile efficiencies are unaltered by several years of endurance training in young adults, and 2) the training-induced improvement in mitochondrial energetic capacity appears to be independent from changes in mitochondrial coupling.
    Mots-clés : crmbm, msk.

  • Le Troter, A, Fouré, A, Guye, M, Confort-Gouny, S, Mattei, J-P, Gondin, J, Salort-Campana, E & Bendahan, D 2016, “Volume measurements of individual muscles in human quadriceps femoris using atlas-based segmentation approaches”, Magma (New York, N.Y.), vol. 29, no. 2, p. 245-257.
    Résumé : OBJECTIVES: Atlas-based segmentation is a powerful method for automatic structural segmentation of several sub-structures in many organs. However, such an approach has been very scarcely used in the context of muscle segmentation, and so far no study has assessed such a method for the automatic delineation of individual muscles of the quadriceps femoris (QF). In the present study, we have evaluated a fully automated multi-atlas method and a semi-automated single-atlas method for the segmentation and volume quantification of the four muscles of the QF and for the QF as a whole. SUBJECTS AND METHODS: The study was conducted in 32 young healthy males, using high-resolution magnetic resonance images (MRI) of the thigh. The multi-atlas-based segmentation method was conducted in 25 subjects. Different non-linear registration approaches based on free-form deformable (FFD) and symmetric diffeomorphic normalization algorithms (SyN) were assessed. Optimal parameters of two fusion methods, i.e., STAPLE and STEPS, were determined on the basis of the highest Dice similarity index (DSI) considering manual segmentation (MSeg) as the ground truth. Validation and reproducibility of this pipeline were determined using another MRI dataset recorded in seven healthy male subjects on the basis of additional metrics such as the muscle volume similarity values, intraclass coefficient, and coefficient of variation. Both non-linear registration methods (FFD and SyN) were also evaluated as part of a single-atlas strategy in order to assess longitudinal muscle volume measurements. The multi- and the single-atlas approaches were compared for the segmentation and the volume quantification of the four muscles of the QF and for the QF as a whole. RESULTS: Considering each muscle of the QF, the DSI of the multi-atlas-based approach was high 0.87 ± 0.11 and the best results were obtained with the combination of two deformation fields resulting from the SyN registration method and the STEPS fusion algorithm. The optimal variables for FFD and SyN registration methods were four templates and a kernel standard deviation ranging between 5 and 8. The segmentation process using a single-atlas-based method was more robust with DSI values higher than 0.9. From the vantage of muscle volume measurements, the multi-atlas-based strategy provided acceptable results regarding the QF muscle as a whole but highly variable results regarding individual muscle. On the contrary, the performance of the single-atlas-based pipeline for individual muscles was highly comparable to the MSeg, thereby indicating that this method would be adequate for longitudinal tracking of muscle volume changes in healthy subjects. CONCLUSION: In the present study, we demonstrated that both multi-atlas and single-atlas approaches were relevant for the segmentation of individual muscles of the QF in healthy subjects. Considering muscle volume measurements, the single-atlas method provided promising perspectives regarding longitudinal quantification of individual muscle volumes.
    Mots-clés : crmbm, Fusion, Individual muscle volume measurements, MRI, msk, Multi-atlas-based segmentation, Non-linear registration, Quadriceps femoris muscle.

  • Martin, A, Grosprêtre, S, Vilmen, C, Guye, M, Mattei, J-P, LE Fur, Y, Bendahan, D & Gondin, J 2016, “The Etiology of Muscle Fatigue Differs between Two Electrical Stimulation Protocols”, Medicine and Science in Sports and Exercise, vol. 48, no. 8, p. 1474-1484.
    Résumé : PURPOSE: This study aimed at investigating the mechanisms involved in the force reduction induced by two electrical stimulation (ES) protocols that were designed to activate motor units differently. METHODS: The triceps surae of 11 healthy subjects (8 men; age, ~28 yr) was activated using ES applied over the tibial nerve. Two ES protocols (conventional [CONV]: 20 Hz, 0.05 ms vs wide-pulse high-frequency [WPHF]: 80 Hz, 1 ms) were performed and involved 40 trains (6 s on-6 s off) delivered at an intensity (IES) evoking 20% of maximal voluntary contraction. To analyze the mechanical properties of the motor units activated at IES, force-frequency relation was evoked before and after each protocol. H-reflex and M-wave responses evoked by the last stimulation pulse were also assessed during each ES protocol. Electromyographic responses (∑EMG) were recorded after each train to analyze the behavior of the motor units activated at IES. Metabolic variables, including relative concentrations of phosphocreatine and inorganic phosphate as well as intracellular pH, were assessed using P-MR spectroscopy during each protocol. RESULTS: Larger H-reflex amplitudes were observed during WPHF as compared with CONV, whereas opposite findings were observed for M-wave amplitudes. Despite this difference, both the force reduction (-26%) and metabolic changes were similar between the two protocols. The CONV protocol induced a rightward shift of the force-frequency relation, whereas a significant reduction of the ∑EMG evoked at IES was observed only for the WPHF. CONCLUSIONS: These results suggest that a decreased number of active motor units mainly contributed to WPHF-induced force decrease, whereas intracellular processes were most likely involved in the force reduction occurring during CONV stimulation.
    Mots-clés : crmbm, msk.

  • Sdika, M, Tonson, A, Le Fur, Y, Cozzone, PJ & Bendahan, D 2016, “Multi-atlas-based fully automatic segmentation of individual muscles in rat leg”, Magma (New York, N.Y.), vol. 29, no. 2, p. 223-235.
    Résumé : OBJECTIVE: To quantify individual muscle volume in rat leg MR images using a fully automatic multi-atlas-based segmentation method. MATERIALS AND METHODS: We optimized a multi-atlas-based segmentation method to take into account the voxel anisotropy of numbers of MRI acquisition protocols. We mainly tested an image upsampling process along Z and a constraint on the nonlinear deformation in the XY plane. We also evaluated a weighted vote procedure and an original implementation of an artificial atlas addition. Using this approach, we measured gastrocnemius and plantaris muscle volumes and compared the results with manual segmentation. The method reliability for volume quantification was evaluated using the relative overlap index. RESULTS: The most accurate segmentation was obtained using a nonlinear registration constrained in the XY plane by zeroing the Z component of the displacement and a weighted vote procedure for both muscles regardless of the number of atlases. The performance of the automatic segmentation and the corresponding volume quantification outperformed the interoperator variability using a minimum of three original atlases. CONCLUSION: We demonstrated the reliability of a multi-atlas segmentation approach for the automatic segmentation and volume quantification of individual muscles in rat leg and found that constraining the registration in plane significantly improved the results.
    Mots-clés : Anisotropy, crmbm, Magnetic Resonance Imaging, msk, Multi-atlas, rat, Reproducibility of Results, Segmentation, skeletal muscle.


Journal Article

  • Fouré, A, Duhamel, G, Wegrzyk, J, Boudinet, H, Mattei, J-P, Le Troter, A, Bendahan, D & Gondin, J 2015, “Heterogeneity of muscle damage induced by electrostimulation: a multimodal MRI study”, Medicine and Science in Sports and Exercise, vol. 47, no. 1, p. 166-175.
    Résumé : PURPOSE: Neuromuscular electrostimulation (NMES) leads to a spatially fixed, synchronous, and superficial motor unit recruitment, which could induce muscle damage. Therefore, the extent of muscle damage and its spatial occurrence were expected to be heterogeneous across and along the quadriceps femoris (QF) muscles. The aim of the present study was to characterize muscle spatial heterogeneity in QF damage after a single bout of isometric NMES using multimodal magnetic resonance imaging (MRI). METHODS: Twenty-five young healthy males participated in this study. MRI investigations consisted of the assessment of muscle volume, transverse relaxation time (T2), and diffusion tensor imaging (DTI) in muscles positioned near the stimulation electrodes (i.e., vastus lateralis (VL) and vastus medialis (VM)) and muscles located outside the stimulated regions (i.e., vastus intermedius and rectus femoris). These measurements were performed 6 d before, and 2 d and 4 d (D4) after the NMES session. RESULTS: For the muscles placed in direct contact with the stimulation electrodes, volume (VL, +8.5%; VM, +3.8%), T2 (VL, +19.5%; VM, +6.7%) and radial diffusivity (λ3) (VL, + 7.3%; VM, +3.7%) significantly increased at D4. Whereas MRI parameter changes were larger for VL as compared with those for other QF muscles at D4, homogeneous alterations were found along all QF muscles. CONCLUSIONS: Isometric NMES induced specific and localized alterations in VL and VM, with heterogeneous damage amplitude among them. Potential effects of unaccustomed intermuscle shear stress during electrically evoked isometric contractions could be a key factor in the spatial occurrence and the extent of damage among QF muscles (especially in VL). The kinetics and extent of MRI changes varied between T2 and diffusion tensor imaging metrics, suggesting the involvement of different physiological processes.
    Mots-clés : crmbm, msk.

  • Fouré, A, Le Troter, A, Guye, M, Mattei, J-P, Bendahan, D & Gondin, J 2015, “Localization and quantification of intramuscular damage using statistical parametric mapping and skeletal muscle parcellation”, Scientific Reports, vol. 5, p. 18580.
    Résumé : In the present study, we proposed an original and robust methodology which combines the spatial normalization of skeletal muscle images, the statistical parametric mapping (SPM) analysis and the use of a specific parcellation in order to accurately localize and quantify the extent of skeletal muscle damage within the four heads of the quadriceps femoris. T2 maps of thigh muscles were characterized before, two (D2) and four (D4) days after 40 maximal isometric electrically-evoked contractions in 25 healthy young males. On the basis of SPM analysis of coregistrated T2 maps, the alterations were similarly detected at D2 and D4 in the superficial and distal regions of the vastus medialis (VM) whereas the proportion of altered muscle was higher in deep muscle regions of the vastus lateralis at D4 (deep: 35 ± 25%, superficial: 23 ± 15%) as compared to D2 (deep: 18 ± 13%, superficial: 17 ± 13%). The present methodology used for the first time on skeletal muscle would be of utmost interest to detect subtle intramuscular alterations not only for the diagnosis of muscular diseases but also for assessing the efficacy of potential therapeutic interventions and clinical treatment strategies.
    Mots-clés : crmbm, msk.

  • Fouré, A, Wegrzyk, J, LE Fur, Y, Mattei, J-P, Boudinet, H, Vilmen, C, Bendahan, D & Gondin, J 2015, “Impaired mitochondrial function and reduced energy cost as a result of muscle damage”, Medicine and Science in Sports and Exercise, vol. 47, no. 6, p. 1135-1144.
    Résumé : PURPOSE: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remain to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise, but the magnitude of muscle energetics alterations for NMES EIMD has never been documented. METHODS: P magnetic resonance spectroscopy measurements were performed in 13 young healthy males during a standardized rest-exercise-recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec). RESULTS: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly owing to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%). CONCLUSION: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of noncontractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.
    Mots-clés : crmbm, msk.

  • Gondin, J, Théret, M, Duhamel, G, Pegan, K, Mathieu, JRR, Peyssonnaux, C, Cuvellier, S, Latroche, C, Chazaud, B, Bendahan, D & Mounier, R 2015, “Myeloid HIFs Are Dispensable for Resolution of Inflammation during Skeletal Muscle Regeneration”, The Journal of Immunology, vol. 194, no. 7, p. 3389-3399, viewed 5October,2015, .
    Résumé : Besides their role in cellular responses to hypoxia, hypoxia-inducible factors (HIFs) are involved in innate immunity and also have anti-inflammatory (M2) functions, such as resolution of inflammation preceding healing. Whereas the first steps of the inflammatory response are associated with proinflammatory (M1) macrophages (MPs), resolution of inflammation is associated with anti-inflammatory MPs exhibiting an M2 phenotype. This M1 to M2 sequence is observed during postinjury muscle regeneration, which provides an excellent paradigm to study the resolution of sterile inflammation. In this study, using in vitro and in vivo approaches in murine models, we demonstrated that deletion of hif1a or hif2a in MPs has no impact on the acquisition of an M2 phenotype. Furthermore, using a multiscale methodological approach, we showed that muscles did not require macrophagic hif1a or hif2a to regenerate. These results indicate that macrophagic HIFs do not play a crucial role during skeletal muscle regeneration induced by sterile tissue damage.
    Mots-clés : crmbm, msk.

  • Jubeau, M, LE Fur, Y, Duhamel, G, Wegrzyk, J, Confort-Gouny, S, Vilmen, C, Cozzone, PJ, Mattei, JP, Bendahan, D & Gondin, J 2015, “Localized metabolic and t2 changes induced by voluntary and evoked contractions”, Medicine and Science in Sports and Exercise, vol. 47, no. 5, p. 921-930.
    Résumé : PURPOSE: This study compared the metabolic and activation changes induced by electrically evoked (neuromuscular electrical stimulation (NMES)) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations. METHODS: Fifteen healthy subjects were asked to perform both NMES and VOL protocols with the knee extensors (i.e., 232 isometric contractions at 30% of maximal force) inside a 3-T scanner for two experimental sessions. During the first session, metabolic variations, i.e., phosphocreatine (PCr), inorganic phosphate (Pi), and pH, were recorded using localized P CSI. During a second session, T2 maps of the knee extensors were obtained at rest and immediately after each exercise. Voxels of interest were selected from the directly stimulated vastus lateralis and from the nondirectly stimulated rectus femoris/vastus intermedius muscles. RESULTS: PCr depletion recorded throughout the NMES session was significantly larger in the vastus lateralis as compared with the rectus femoris/vastus intermedius muscles for both conditions (VOL and NMES). A higher occurrence of Pi splitting and a greater acidosis was found during NMES as compared with VOL exercise, illustrating the heterogeneous activation of both slow and fast muscle fibers. T2 changes were greater after NMES as compared with VOL for both muscles but were not necessarily related to the localized metabolic demand. CONCLUSION: We provided direct evidence that the metabolic demand was strongly related to both the exercise modality and the site of stimulation. On the basis of the occurrence of Pi splitting, we suggested that NMES can activate fast muscle fibers even at low force levels.
    Mots-clés : crmbm, msk.

  • Lareau-Trudel, E, Le Troter, A, Ghattas, B, Pouget, J, Attarian, S, Bendahan, D & Salort-Campana, E 2015, “Muscle Quantitative MR Imaging and Clustering Analysis in Patients with Facioscapulohumeral Muscular Dystrophy Type 1”, PloS One, vol. 10, no. 7, p. e0132717.
    Résumé : BACKGROUND: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is the third most common inherited muscular dystrophy. Considering the highly variable clinical expression and the slow disease progression, sensitive outcome measures would be of interest. METHODS AND FINDINGS: Using muscle MRI, we assessed muscular fatty infiltration in the lower limbs of 35 FSHD1 patients and 22 healthy volunteers by two methods: a quantitative imaging (qMRI) combined with a dedicated automated segmentation method performed on both thighs and a standard T1-weighted four-point visual scale (visual score) on thighs and legs. Each patient had a clinical evaluation including manual muscular testing, Clinical Severity Score (CSS) scale and MFM scale. The intramuscular fat fraction measured using qMRI in the thighs was significantly higher in patients (21.9 ± 20.4%) than in volunteers (3.6 ± 2.8%) (p<0.001). In patients, the intramuscular fat fraction was significantly correlated with the muscular fatty infiltration in the thighs evaluated by the mean visual score (p<0.001). However, we observed a ceiling effect of the visual score for patients with a severe fatty infiltration clearly indicating the larger accuracy of the qMRI approach. Mean intramuscular fat fraction was significantly correlated with CSS scale (p ≤ 0.01) and was inversely correlated with MMT score, MFM subscore D1 (p ≤ 0.01) further illustrating the sensitivity of the qMRI approach. Overall, a clustering analysis disclosed three different imaging patterns of muscle involvement for the thighs and the legs which could be related to different stages of the disease and put forth muscles which could be of interest for a subtle investigation of the disease progression and/or the efficiency of any therapeutic strategy. CONCLUSION: The qMRI provides a sensitive measurement of fat fraction which should also be of high interest to assess disease progression and any therapeutic strategy in FSHD1 patients.
    Mots-clés : Adipose Tissue, Adult, Case-Control Studies, Cluster Analysis, crmbm, Disease Progression, Female, Humans, Leg, Magnetic Resonance Imaging, Male, Middle Aged, msk, Muscle, Skeletal, Muscular Dystrophy, Facioscapulohumeral, Severity of Illness Index, Thigh.

  • Layec, G, Bringard, A, Le Fur, Y, Micallef, J-P, Vilmen, C, Perrey, S, Cozzone, PJ & Bendahan, D 2015, “Opposite effects of hyperoxia on mitochondrial and contractile efficiency in human quadriceps muscles”, American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 308, no. 8, p. R724-733.
    Résumé : Exercise efficiency is an important determinant of exercise capacity. However, little is known about the physiological factors that can modulate muscle efficiency during exercise. We examined whether improved O2 availability would 1) impair mitochondrial efficiency and shift the energy production toward aerobic ATP synthesis and 2) reduce the ATP cost of dynamic contraction owing to an improved neuromuscular efficiency, such that 3) whole body O2 cost would remain unchanged. We used (31)P-magnetic resonance spectroscopy, surface electromyography, and pulmonary O2 consumption (V̇o2p) measurements in eight active subjects during 6 min of dynamic knee-extension exercise under different fractions of inspired O2 (FiO2 , 0.21 in normoxia and 1.0 in hyperoxia). V̇o2p (755 ± 111 ml/min in normoxia and 799 ± 188 ml/min in hyperoxia, P > 0.05) and O2 cost (P > 0.05) were not significantly different between normoxia and hyperoxia. In contrast, the total ATP synthesis rate and the ATP cost of dynamic contraction were significantly lower in hyperoxia than normoxia (P < 0.05). As a result, the ratio of the rate of oxidative ATP synthesis from the quadriceps to V̇o2p was lower in hyperoxia than normoxia but did not reach statistical significance (16 ± 3 mM/ml in normoxia and 12 ± 5 mM/ml in hyperoxia, P = 0.07). Together, these findings reveal dynamic and independent regulations of mitochondrial and contractile efficiency as a consequence of O2 availability in young active individuals. Furthermore, muscle efficiency appears to be already optimized in normoxia and is unlikely to contribute to the well-established improvement in exercise capacity induced by hyperoxia.
    Mots-clés : 31P-magnetic resonance spectroscopy, Adenosine Triphosphate, Adult, Bicycling, crmbm, Electromyography, Energy Metabolism, Exercise, Exercise Tolerance, Female, Humans, Hydrogen-Ion Concentration, Hyperoxia, Isometric Contraction, Lung, Magnetic Resonance Spectroscopy, Male, Mitochondria, Mitochondria, Muscle, msk, muscle efficiency, Muscle energetics, Muscle Fatigue, Muscle Strength, O2 availability, Oxygen Consumption, Quadriceps Muscle, Time Factors.

  • Macia, M, Pecchi, E, Vilmen, C, Desrois, M, Lan, C, Portha, B, Bernard, M, Bendahan, D & Giannesini, B 2015, “Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo”, PloS One, vol. 10, no. 6, p. e0129579.
    Résumé : Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM) development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK) rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA). Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator). During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz), mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.
    Mots-clés : crmbm, cvs, msk.

  • Park, JM, Josan, S, Mayer, D, Hurd, RE, Chung, Y, Bendahan, D, Spielman, DM & Jue, T 2015, “Hyperpolarized 13C NMR observation of lactate kinetics in skeletal muscle”, The Journal of Experimental Biology, vol. 218, no. Pt 20, p. 3308-3318.
    Résumé : The production of glycolytic end products, such as lactate, usually evokes a cellular shift from aerobic to anaerobic ATP generation and O2 insufficiency. In the classical view, muscle lactate must be exported to the liver for clearance. However, lactate also forms under well-oxygenated conditions, and this has led investigators to postulate lactate shuttling from non-oxidative to oxidative muscle fiber, where it can serve as a precursor. Indeed, the intracellular lactate shuttle and the glycogen shunt hypotheses expand the vision to include a dynamic mobilization and utilization of lactate during a muscle contraction cycle. Testing the tenability of these provocative ideas during a rapid contraction cycle has posed a technical challenge. The present study reports the use of hyperpolarized [1-(13)C]lactate and [2-(13)C]pyruvate in dynamic nuclear polarization (DNP) NMR experiments to measure the rapid pyruvate and lactate kinetics in rat muscle. With a 3 s temporal resolution, (13)C DNP NMR detects both [1-(13)C]lactate and [2-(13)C]pyruvate kinetics in muscle. Infusion of dichloroacetate stimulates pyruvate dehydrogenase activity and shifts the kinetics toward oxidative metabolism. Bicarbonate formation from [1-(13)C]lactate increases sharply and acetyl-l-carnitine, acetoacetate and glutamate levels also rise. Such a quick mobilization of pyruvate and lactate toward oxidative metabolism supports the postulated role of lactate in the glycogen shunt and the intracellular lactate shuttle models. The study thus introduces an innovative DNP approach to measure metabolite transients, which will help delineate the cellular and physiological role of lactate and glycolytic end products.
    Mots-clés : Hyperpolarized 13C, Lactate bioenergetics, msk, Muscle metabolism, Pyruvate.

  • Wegrzyk, J, Fouré, A, Le Fur, Y, Maffiuletti, NA, Vilmen, C, Guye, M, Mattei, J-P, Place, N, Bendahan, D & Gondin, J 2015, “Responders to Wide-Pulse, High-Frequency Neuromuscular Electrical Stimulation Show Reduced Metabolic Demand: A 31P-MRS Study in Humans”, PloS One, vol. 10, no. 11, p. e0143972.
    Résumé : Conventional (CONV) neuromuscular electrical stimulation (NMES) (i.e., short pulse duration, low frequencies) induces a higher energetic response as compared to voluntary contractions (VOL). In contrast, wide-pulse, high-frequency (WPHF) NMES might elicit-at least in some subjects (i.e., responders)-a different motor unit recruitment compared to CONV that resembles the physiological muscle activation pattern of VOL. We therefore hypothesized that for these responder subjects, the metabolic demand of WPHF would be lower than CONV and comparable to VOL. 18 healthy subjects performed isometric plantar flexions at 10% of their maximal voluntary contraction force for CONV (25 Hz, 0.05 ms), WPHF (100 Hz, 1 ms) and VOL protocols. For each protocol, force time integral (FTI) was quantified and subjects were classified as responders and non-responders to WPHF based on k-means clustering analysis. Furthermore, a fatigue index based on FTI loss at the end of each protocol compared with the beginning of the protocol was calculated. Phosphocreatine depletion (ΔPCr) was assessed using 31P magnetic resonance spectroscopy. Responders developed four times higher FTI's during WPHF (99 ± 37 ×103 N.s) than non-responders (26 ± 12 ×103 N.s). For both responders and non-responders, CONV was metabolically more demanding than VOL when ΔPCr was expressed relative to the FTI. Only for the responder group, the ∆PCr/FTI ratio of WPHF (0.74 ± 0.19 M/N.s) was significantly lower compared to CONV (1.48 ± 0.46 M/N.s) but similar to VOL (0.65 ± 0.21 M/N.s). Moreover, the fatigue index was not different between WPHF (-16%) and CONV (-25%) for the responders. WPHF could therefore be considered as the less demanding NMES modality-at least in this subgroup of subjects-by possibly exhibiting a muscle activation pattern similar to VOL contractions.
    Mots-clés : crmbm, msk.
  • Wegrzyk, J, Foure, A, Vilmen, C, Ghattas, B, Maffiuletti, NA, Mattei, J-P, Place, N, Bendahan, D & Gondin, J 2015, “Extra Forces induced by wide-pulse, high-frequency electrical stimulation: Occurrence, magnitude, variability and underlying mechanisms”, Clinical Neurophysiology, vol. 126, no. 7, p. 1400-1412.
    Résumé : Objective: In contrast to conventional (CONV) neuromuscular electrical stimulation (NMES), the use of "wide-pulse, high-frequencies" (WPHF) can generate higher forces than expected by the direct activation of motor axons alone. We aimed at investigating the occurrence, magnitude, variability and underlying neuromuscular mechanisms of these "Extra Forces" (EF). Methods: Electrically-evoked isometric plantar flexion force was recorded in 42 healthy subjects. Additionally, twitch potentiation, H-reflex and M-wave responses were assessed in 13 participants. CONV (25 Hz, 0.05 ms) and WPHF (100 Hz, 1 ms) NMES consisted of five stimulation trains (20 s on-90 s off). Results: K-means clustering analysis disclosed a responder rate of almost 60%. Within this group of responders, force significantly increased from 4% to 16% of the maximal voluntary contraction force and H-reflexes were depressed after WPHF NMES. In contrast, non-responders showed neither EF nor H-reflex depression. Twitch potentiation and resting EMG data were similar between groups. Interestingly, a large inter-and intrasubject variability of EF was observed. Conclusion: The responder percentage was overestimated in previous studies. Significance: This study proposes a novel methodological framework for unraveling the neurophysiological mechanisms involved in EF and provides further evidence for a central contribution to EF in responders. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Mots-clés : Adult, Cluster Analysis, crmbm, Electric Stimulation, Electromyography, EMG, Evoked Potentials, Extra Forces, Female, H-Reflex, Humans, Male, msk, Muscle Contraction, Muscle Strength, Muscle, Skeletal, NMES, NMES, Extra Forces, Triceps surae, Responder, EMG, plateau-like behavior, spinal-cord-injury, post-activation depression, human skeletal-muscle, catch-like property, soleus h-reflex, neuromuscular stimulation, triceps surae, m-waves, presynaptic inhibition, Responder, Single-Blind Method, Triceps surae.

  • Yashiro, K, Tonson, A, Pecchi, É, Vilmen, C, Le Fur, Y, Bernard, M, Bendahan, D & Giannesini, B 2015, “Capsiate Supplementation Reduces Oxidative Cost of Contraction in Exercising Mouse Skeletal Muscle In Vivo”, PloS One, vol. 10, no. 6, p. e0128016.
    Résumé : Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.
    Mots-clés : crmbm, cvs.


Journal Article

  • Fouré, A, Nosaka, K, Wegrzyk, J, Duhamel, G, Le Troter, A, Boudinet, H, Mattei, J-P, Vilmen, C, Jubeau, M, Bendahan, D & Gondin, J 2014, “Time course of central and peripheral alterations after isometric neuromuscular electrical stimulation-induced muscle damage”, PloS One, vol. 9, no. 9, p. e107298.
    Résumé : Isometric contractions induced by neuromuscular electrostimulation (NMES) have been shown to result in a prolonged force decrease but the time course of the potential central and peripheral factors have never been investigated. This study examined the specific time course of central and peripheral factors after isometric NMES-induced muscle damage. Twenty-five young healthy men were subjected to an NMES exercise consisting of 40 contractions for both legs. Changes in maximal voluntary contraction force of the knee extensors (MVC), peak evoked force during double stimulations at 10 Hz (Db10) and 100 Hz (Db100), its ratio (10∶100), voluntary activation, muscle soreness and plasma creatine kinase activity were assessed before, immediately after and throughout four days after NMES session. Changes in knee extensors volume and T2 relaxation time were also assessed at two (D2) and four (D4) days post-exercise. MVC decreased by 29% immediately after NMES session and was still 19% lower than the baseline value at D4. The decrease in Db10 was higher than in Db100 immediately and one day post-exercise resulting in a decrease (-12%) in the 10∶100 ratio. On the contrary, voluntary activation significantly decreased at D2 (-5%) and was still depressed at D4 (-5%). Muscle soreness and plasma creatine kinase activity increased after NMES and peaked at D2 and D4, respectively. T2 was also increased at D2 (6%) and D4 (9%). Additionally, changes in MVC and peripheral factors (e.g., Db100) were correlated on the full recovery period, while a significant correlation was found between changes in MVC and VA only from D2 to D4. The decrease in MVC recorded immediately after the NMES session was mainly due to peripheral changes while both central and peripheral contributions were involved in the prolonged force reduction. Interestingly, the chronological events differ from what has been reported so far for voluntary exercise-induced muscle damage.
    Mots-clés : Adult, crmbm, Electric Stimulation, Electromyography, Exercise, Humans, Isometric Contraction, Knee, Male, Muscle Contraction, Muscle Fatigue, Neuromuscular Diseases.

  • Gineste, C, Ottenheijm, C, Le Fur, Y, Banzet, S, Pecchi, E, Vilmen, C, Cozzone, PJ, Koulmann, N, Hardeman, EC, Bendahan, D & Gondin, J 2014, “Alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of nemaline myopathy”, PloS One, vol. 9, no. 9, p. e109066.
    Résumé : Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8-9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.
    Mots-clés : crmbm.

  • Goislard de Monsabert, B, Vigouroux, L, Bendahan, D & Berton, E 2014, “Quantification of finger joint loadings using musculoskeletal modelling clarifies mechanical risk factors of hand osteoarthritis”, Medical Engineering and Physics, vol. 36, no. 2, p. 177-184, viewed 29October,2014, .
    Résumé : Owing to limited quantitative data related to the loadings (forces and pressures) acting upon finger joints, several clinical observations regarding mechanical risk factors of hand osteoarthritis remain misunderstood. To improve the knowledge of this pathology, the present study used musculoskeletal modelling to quantify the forces and pressures acting upon hand joints during two grasping tasks. Kinematic and grip force data were recorded during both a pinch and a power grip tasks. Three-dimensional magnetic resonance imaging measurements were conducted to quantify joint contact areas. Using these datasets as input, a musculoskeletal model of the hand and wrist, including twenty-three degrees of freedom and forty-two muscles, has been developed to estimate joint forces and joint pressures. When compared with the power grip task, the pinch grip task resulted in two to eight times higher joint loadings whereas the grip forces exerted on each finger were twice lower. For both tasks, joint forces and pressures increased along a disto-proximal direction for each finger. The quantitative dataset provided by the present hand model clarified two clinical observations about osteoarthritis development which were not fully understood, i.e., the strong risk associated to pinch grip tasks and the high frequency of thumb-base osteoarthritis.
    Mots-clés : Hand, Joint pressure, Musculoskeletal modelling, Osteoarthritis, Pinch grip, Power grip.

  • Gondin, J, Vilmen, C, Cozzone, PJ, Bendahan, D & Duhamel, G 2014, “High-field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non-invasive combined stimulation and force measurement device”, NMR in biomedicine, vol. 27, no. 8, p. 870-879.
    Résumé : We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2 -weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high-field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions.
    Mots-clés : crmbm.

  • Kazuya, Y, Tonson, A, Pecchi, E, Dalmasso, C, Vilmen, C, Fur, YL, Bernard, M, Bendahan, D & Giannesini, B 2014, “A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle”, American Journal of Physiology. Endocrinology and Metabolism, vol. 306, no. 10, p. E1110-1119.
    Résumé : Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.
    Mots-clés : Animals, Biomechanical Phenomena, Capsaicin, Cells, Cultured, crmbm, Electric Stimulation, Energy Metabolism, Male, Mice, Mice, Inbred C57BL, Muscle Contraction, Muscle, Skeletal, Physical Conditioning, Animal.
    Attachment Full Text PDF 307.6 kb (source)

  • Marcotorchino, J, Tourniaire, F, Astier, J, Karkeni, E, Canault, M, Amiot, M-J, Bendahan, D, Bernard, M, Martin, J-C, Giannesini, B & Landrier, J-F 2014, “Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation”, The Journal of Nutritional Biochemistry, vol. 25, no. 10, p. 1077-1083.
    Résumé : Prospective studies reported an inverse correlation between 25-hydroxyvitamin D [25(OH)D] plasma levels and prevalence of obesity and type 2 diabetes. In addition, 25(OH)D status may be a determinant of obesity onset. However, the causality between these observations is not yet established. We studied the preventive effect of vitamin D3 (VD3) supplementation (15,000IU/kg of food for 10weeks) on onset of obesity in a diet-induced obesity mouse model. We showed that the VD3 supplementation limited weight gain induced by high-fat diet, which paralleled with an improvement of glucose homeostasis. The limitation of weight gain could further be explained by an increased lipid oxidation, possibly due to an up-regulation of genes involved in fatty acid oxidation and mitochondrial metabolism, leading to increased energy expenditure. Altogether, these data show that VD3 regulates energy expenditure and suggest that VD3 supplementation may represent a strategy of preventive nutrition to fight the onset of obesity and associated metabolic disorders.

  • Ratel, S, Tonson, A, Cozzone, PJ & Bendahan, D 2014, “The rate of PCr resynthesis is not a reliable index of skeletal muscle oxidative capacity”, European Journal of Applied Physiology, vol. 114, no. 1, p. 217-218, viewed 29October,2014, .
    Résumé : Dear Editor,We have read with much interest the paper recently published by Kappenstein et al. (2013) regarding changes in phosphocreatine concentration in skeletal muscle of children and adults during high-intensity intermittent exercise. Although the results of this investigation are of potential interest, we are actually concerned about the utilization of the time constant of PCr recovery (τPCr) as a simple index of mitochondrial function and the corresponding interpretation regarding borderline differences in τPCr values between children and adults.In their paper, Kappenstein et al. (2013) reported lower τPCr values in children, which became statistically significant when the smallest and highest values were eliminated. Although the authors mentioned that the borderline difference in τPCr values between children and adults might be attributed to a temporary inhibition of oxidative phosphorylation in adults during the early post-exercise recovery period, they did not take into accou ...
    Mots-clés : crmbm, Human Physiology, Occupational Medicine/Industrial Medicine, Sports Medicine.

  • Relizani, K, Mouisel, E, Giannesini, B, Hourdé, C, Patel, K, Morales Gonzalez, S, Jülich, K, Vignaud, A, Piétri-Rouxel, F, Fortin, D, Garcia, L, Blot, S, Ritvos, O, Bendahan, D, Ferry, A, Ventura-Clapier, R, Schuelke, M & Amthor, H 2014, “Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy”, Molecular Therapy: The Journal of the American Society of Gene Therapy, vol. 22, no. 8, p. 1423-1433.
    Résumé : Myostatin regulates skeletal muscle size via the activin receptor IIB (ActRIIB). However, its effect on muscle energy metabolism and energy-dependent muscle function remains largely unexplored. This question needs to be solved urgently since various therapies for neuromuscular diseases based on blockade of ActRIIB signaling are being developed. Here, we show in mice, that 4-month pharmacological abrogation of ActRIIB signaling by treatment with soluble ActRIIB-Fc triggers extreme muscle fatigability. This is associated with elevated serum lactate levels and a severe metabolic myopathy in the mdx mouse, an animal model of Duchenne muscular dystrophy. Blockade of ActRIIB signaling downregulates porin, a crucial ADP/ATP shuttle between cytosol and mitochondrial matrix leading to a consecutive deficiency of oxidative phosphorylation as measured by in vivo Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Further, ActRIIB blockade reduces muscle capillarization, which further compounds the metabolic stress. We show that ActRIIB regulates key determinants of muscle metabolism, such as Pparβ, Pgc1α, and Pdk4 thereby optimizing different components of muscle energy metabolism. In conclusion, ActRIIB signaling endows skeletal muscle with high oxidative capacity and low fatigability. The severe metabolic side effects following ActRIIB blockade caution against deploying this strategy, at least in isolation, for treatment of neuromuscular disorders.

  • Sagui, E, Abriat, A, Kozak-Ribbens, G, Foutrier-Morello, C, Bernard, M, Canini, F, Brosset, C & Bendahan, D 2014, “Is muscle energy production disturbed in exertional heat stroke?”, Military Medicine, vol. 179, no. 3, p. 342-345.
    Résumé : BACKGROUND: Exertional heat stroke (EHS) is a life-threatening disease that shares some clinical similarities with malignant hyperthermia (MH). By use of (31)Phosphorus magnetic resonance spectroscopy (MRS), EHS patients with MH susceptibility and MH patients shared common metabolic abnormalities. The aim of this study was to determine whether subjects who suffered from an EHS episode had disturbed muscle energetics. METHOD: This retrospective study was performed within the French database of military subjects that were explored from 2004 to 2010 after they suffered an EHS. All subjects had both in vitro contracture test to determine their MH susceptibility and (31)Phosphorus MRS at 4.7 Tesla to assess muscle energetics by means of MRS score, a composite score corresponding to the sum of metabolic abnormalities recorded during a standardized rest-exercise-recovery protocol. RESULTS: 437 subjects were investigated and 32.5% of them exhibited abnormal MRS score. MRS score did not segregate subjects on demographic, clinical, or biological grounds. No clear correlation could be done between MH status and MRS score. DISCUSSION: These results did not confirm the potential relationship between calcium homeostasis and muscle energetics previously reported. However, muscle energy production was disturbed in a significant number of EHS subjects.
    Mots-clés : crmbm.


Journal Article

  • Giannesini, B, Vilmen, C, Amthor, H, Bernard, M & Bendahan, D 2013, “Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo”, American journal of physiology. Endocrinology and metabolism, vol. 305, no. 1, p. E33-40.
    Résumé : Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.
    Mots-clés : Adenosine Triphosphate, Animals, Biomechanics, crmbm, Electric Stimulation, Energy Metabolism, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Contraction, Muscle, Skeletal, Muscular Atrophy, Myostatin, Physical Conditioning, Animal.

  • Gineste, C, De Winter, JM, Kohl, C, Witt, CC, Giannesini, B, Brohm, K, Le Fur, Y, Gretz, N, Vilmen, C, Pecchi, E, Jubeau, M, Cozzone, PJ, Stienen, GJM, Granzier, H, Labeit, S, Ottenheijm, CAC, Bendahan, D & Gondin, J 2013, “In vivo and in vitro investigations of heterozygous nebulin knock-out mice disclose a mild skeletal muscle phenotype”, Neuromuscular disorders: NMD, vol. 23, no. 4, p. 357-369.
    Résumé : Nemaline myopathy is the most common congenital skeletal muscle disease, and mutations in the nebulin gene account for 50% of all cases. Recent studies suggest that the disease severity might be related to the nebulin expression levels. Considering that mutations in the nebulin gene are typically recessive, one would expect that a single functional nebulin allele would maintain nebulin protein expression which would result in preserved skeletal muscle function. We investigated skeletal muscle function of heterozygous nebulin knock-out (i.e., nebulin(+/-)) mice using a multidisciplinary approach including protein and gene expression analysis and combined in vivo and in vitro force measurements. Skeletal muscle anatomy and energy metabolism were studied strictly non-invasively using magnetic resonance imaging and 31P-magnetic resonance spectroscopy. Maximal force production was reduced by around 16% in isolated muscle of nebulin(+/-) mice while in vivo force generating capacity was preserved. Muscle weakness was associated with a shift toward a slower proteomic phenotype, but was not related to nebulin protein deficiency or to an impaired energy metabolism. Further studies would be warranted in order to determine the mechanisms leading to a mild skeletal muscle phenotype resulting from the expression of a single nebulin allele.
    Mots-clés : Animals, crmbm, Disease Models, Animal, Gene Expression, Heterozygote, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Mice, Mice, Knockout, Muscle Proteins, Muscle Strength, Muscle Weakness, Muscle, Skeletal, Mutation, Myopathies, Nemaline, Phenotype, Severity of Illness Index.
    Note Note
    The following values have no corresponding Zotero field:<br />Author Address: Aix-Marseille Universite, CRMBM, 13005 Marseille, France; CNRS, Centre de Resonance Magnetique Biologique et Medicale (CRMBM), 13005 Marseille, France.<br />C2 - Muscle <br />ET - 2013/02/05<br />
    Note Note
    <p>Gineste, C<br/>De Winter, J M<br/>Kohl, C<br/>Witt, C C<br/>Giannesini, B<br/>Brohm, K<br/>Le Fur, Y<br/>Gretz, N<br/>Vilmen, C<br/>Pecchi, E<br/>Jubeau, M<br/>Cozzone, P J<br/>Stienen, G J M<br/>Granzier, H<br/>Labeit, S<br/>Ottenheijm, C A C<br/>Bendahan, D<br/>Gondin, J<br/>England<br/>Neuromuscular disorders : NMD<br/>Neuromuscul Disord. 2013 Apr;23(4):357-69. doi: 10.1016/j.nmd.2012.12.011. Epub 2013 Feb 1.</p>

  • Gineste, C, Duhamel, G, Le Fur, Y, Vilmen, C, Cozzone, PJ, Nowak, KJ, Bendahan, D & Gondin, J 2013, “Multimodal MRI and (31)P-MRS Investigations of the ACTA1(Asp286Gly) Mouse Model of Nemaline Myopathy Provide Evidence of Impaired In Vivo Muscle Function, Altered Muscle Structure and Disturbed Energy Metabolism”, PloS one, vol. 8, no. 8, p. e72294.
    Résumé : Nemaline myopathy (NM), the most common non-dystrophic congenital disease of skeletal muscle, can be caused by mutations in the skeletal muscle α-actin gene (ACTA1) (~25% of all NM cases and up to 50% of severe forms of NM). Muscle function of the recently generated transgenic mouse model carrying the human Asp286Gly mutation in the ACTA1 gene (Tg(ACTA1)(Asp286Gly)) has been mainly investigated in vitro. Therefore, we aimed at providing a comprehensive picture of the in vivo hindlimb muscle function of Tg(ACTA1)(Asp286Gly) mice by combining strictly noninvasive investigations. Skeletal muscle anatomy (hindlimb muscles, intramuscular fat volumes) and microstructure were studied using multimodal magnetic resonance imaging (Dixon, T2, Diffusion Tensor Imaging [DTI]). Energy metabolism was studied using 31-phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (1-150 Hz) and a fatigue protocol (6 min-1.7 Hz). Tg(ACTA1)(Asp286Gly) mice showed a mild muscle weakness as illustrated by the reduction of both absolute (30%) and specific (15%) maximal force production. Dixon MRI did not show discernable fatty infiltration in Tg(ACTA1)(Asp286Gly) mice indicating that this mouse model does not reproduce human MRI findings. Increased T2 values were observed in Tg(ACTA1)(Asp286Gly) mice and might reflect the occurrence of muscle degeneration/regeneration process. Interestingly, T2 values were linearly related to muscle weakness. DTI experiments indicated lower λ2 and λ3 values in Tg(ACTA1)(Asp286Gly) mice, which might be associated to muscle atrophy and/or the presence of histological anomalies. Finally (31)P-MRS investigations illustrated an increased anaerobic energy cost of contraction in Tg(ACTA1)(Asp286Gly) mice, which might be ascribed to contractile and non-contractile processes. Overall, we provide a unique set of information about the anatomic, metabolic and functional consequences of the Asp286Gly mutation that might be considered as relevant biomarkers for monitoring the severity and/or the progression of NM and for assessing the efficacy of potential therapeutic interventions.
    Mots-clés : crmbm.

  • Gineste, C, Le Fur, Y, Vilmen, C, Le Troter, A, Pecchi, E, Cozzone, PJ, Hardeman, EC, Bendahan, D & Gondin, J 2013, “Combined MRI and (31)P-MRS Investigations of the ACTA1(H40Y) Mouse Model of Nemaline Myopathy Show Impaired Muscle Function and Altered Energy Metabolism”, PloS one, vol. 8, no. 4, p. e61517.
    Résumé : Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1) account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and (31)Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (-40%) and specific (-25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.
    Mots-clés : Actins, Animals, crmbm, Energy Metabolism, Female, Magnetic Resonance Imaging, Mice, Mice, Mutant Strains, Muscle, Skeletal, Myopathies, Nemaline.

  • Guis, S, Mattei, J-P & Bendahan, D 2013, “Toxic myopathies”, Joint, bone, spine: revue du rhumatisme, vol. 80, no. 3, p. 231-233.
    Mots-clés : crmbm, Humans, Muscular Diseases, Myalgia, Toxins, Biological, Venoms.

  • Layec, G, Malucelli, E, Le Fur, Y, Manners, D, Yashiro, K, Testa, C, Cozzone, PJ, Iotti, S & Bendahan, D 2013, “Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans”, NMR in Biomedicine, vol. 26, no. 11, p. 1403-1411, viewed 29October,2014, .
    Résumé : Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used 31P-magnetic resonance spectroscopy (31P-MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min-1, CVinter-subject = 42%) as compared with PF (46 ± 20 mM min-1, CVinter-subject = 44%) and tended to be higher in FF (43 ± 35 mM min-1, CVinter-subject = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end-exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p <0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end-exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter- and intra-individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates. Copyright © 2013 John Wiley & Sons, Ltd.
    Mots-clés : crmbm, Exercise, Magnetic Resonance Spectroscopy, mitochondrial function, muscle acidosis, muscle oxidative capacity, skeletal muscle.
    Attachment Full Text PDF 264.9 kb (source)
  • Zink, J, Souteyrand, P, Guis, S, Chagnaud, C, Le Fur, Y, Militianu, D, Mattei, JP, Rozenbaum, M, Rosner, I, Boudinet, H, Bernard, M & Bendahan, D 2013, “Semi-Automatic Quantitative Investigation of Wrist Cartilage in Humans Using 3t Mri”, Annals of the Rheumatic Diseases, vol. 72, p. 1018-1019.


Journal Article

  • Bringard, A, Layec, G, Micallef, J-P, Bendahan, D & Perrey, S 2012, “Gas exchange measurements within a magnetic environment: validation of a new system”, Respiratory physiology & neurobiology, vol. 182, no. 1, p. 37-46.
    Résumé : Although simultaneous measurements of pulmonary oxygen uptake (VO2) and Phosphorus-31 magnetic resonance spectroscopy ((31)P MRS) is attractive to investigate muscular metabolism during exercise, the superconducting magnet requires the design of specific gas exchange analyser (GEA). Thus, this study aimed to assess the validity of a commercial GEA system (ZAN600) compatible with (31)P MRS measurements. Using nonmagnetic pneumotachograph and prolonged sampling line (from 2m, control condition, to 6.5m) did not alter the proper synchronisation between flow and gas concentration signals. Also, end-expiratory fraction of O2 (FETO2) and CO(2) (FETCO2), and finally the values of steady-state ventilation (V(E)), carbon dioxide production (VCO2) and VO2 kinetics during moderate knee-extension exercise were not significantly different between 2m and 6.5m conditions and between 6.5m condition inside and outside the magnet. These results showed that a prolonged sampling line used inside the superconducting magnet did not affect the accuracy of VO2 measurements of a commercial GEA system; the latter appears suitable for simultaneous measurements of VO2 and (31)P MRS.
    Mots-clés : Adult, Blood Gas Analysis, Exercise Test, Female, Humans, Magnetic Fields, Magnetic Resonance Spectroscopy, Male, Muscle, Skeletal, Phosphorus Isotopes, Pulmonary Gas Exchange, Reference Values, Respiratory Function Tests.

  • Layec, G, Bringard, A, Yashiro, K, Le Fur, Y, Vilmen, C, Micallef, J-P, Perrey, S, Cozzone, PJ & Bendahan, D 2012, “The slow components of phosphocreatine and pulmonary oxygen uptake can be dissociated during heavy exercise according to training status”, Experimental physiology, vol. 97, no. 8, p. 955-969.
    Résumé : To better understand the mechanisms underlying the pulmonary O(2) uptake (V(O(2P))) slow component during high-intensity exercise, we used (31)P magnetic resonance spectroscopy, gas exchange, surface electromyography and near-infrared spectroscopy measurements to examine the potential relationship between the slow components of V(O(2P)) and phosphocreatine (PCr), muscle recruitment and tissue oxygenation in endurance-trained athletes and sedentary subjects. Specifically, six endurance-trained and seven sedentary subjects performed a dynamic high-intensity exercise protocol during 6 min at an exercise intensity corresponding to 35-40% of knee-extensor maximal voluntary contraction. The slow component of V(O(2P))(117 ± 60 ml min(-1), i.e. 20 ± 10% of the total response) was associated with a paradoxical PCr resynthesis in endurance-trained athletes (-0.90 ± 1.27 mm, i.e. -12 ± 16% of the total response). Meanwhile, oxygenated haemoglobin increased throughout the second part of exercise and was significantly higher at the end of exercise compared with the value at 120 s (P < 0.05), whereas the integrated EMG was not significantly changed throughout exercise. In sedentary subjects, a slow component was simultaneously observed for V(O(2P)) and [PCr] time-dependent changes (208 ± 14 ml min(-1), i.e. 38 ± 18% of the total V(O(2P))response, and 1.82 ± 1.39 mm, i.e. 16 ± 13% of the total [PCr] response), but the corresponding absolute or relative amplitudes were not correlated. The integrated EMG was significantly increased throughout exercise in sedentary subjects. Taken together, our results challenge the hypothesis of a mechanistic link between [PCr] and V(O(2P)) slow components and demonstrate that, as a result of a tighter metabolic control and increased O(2) availability, the [PCr] slow component can be minimized in endurance-trained athletes while the V(O(2P)) slow component occurs.
    Mots-clés : Adult, crmbm, Electromyography, Exercise, Female, Humans, Knee, Magnetic Resonance Spectroscopy, Male, Muscle Contraction, Muscle, Skeletal, Oxygen Consumption, Phosphocreatine, Physical Endurance, Pulmonary Gas Exchange, Sedentary Lifestyle, Young Adult.

  • Ratel, S, Martin, V, Tonson, A, Cozzone, PJ & Bendahan, D 2012, “Skeletal muscle mitochondrial function cannot be properly inferred from PCr resynthesis without taking pH changes into account”, Magnetic resonance imaging, vol. 30, no. 10, p. 1542-1543.
    Mots-clés : crmbm, Female, Humans, Hypothyroidism, Magnetic Resonance Spectroscopy, Male, Muscle, Skeletal, Phosphocreatine.

  • Ratel, S, Martin, V, Tonson, A, Cozzone, PJ & Bendahan, D 2012, “Can we simply infer mitochondrial function from PCr resynthesis after exercise in skeletal muscle?”, Pediatric research, vol. 72, no. 2, p. 221.
    Mots-clés : crmbm, Cystic Fibrosis, Energy Metabolism, Exercise, Female, Humans, Kartagener Syndrome, Male, Muscle, Skeletal.

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