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See detailEccentric muscle contractions: risks and benefits
Hody, Stéphanie ULg; Croisier, Jean-Louis ULg; Lacrosse, Zoé ULg et al

in Proceedings of the Belgian Royal Academies of Medicine (2014)

La contraction musculaire excentrique se caractérise par le développement d'une tension musculaire associée à l'étirement concomitant du complexe musculo-tendineux. Ce mode de contraction présente un ... [more ▼]

La contraction musculaire excentrique se caractérise par le développement d'une tension musculaire associée à l'étirement concomitant du complexe musculo-tendineux. Ce mode de contraction présente un intérêt croissant dans de nombreux domaines tels que l’entraînement sportif, la médecine physique et la rééducation. De plus, certaines indications de l’entraînement en mode excentrique ont été posées chez des patients porteurs de maladies chroniques. Cependant, lorsqu’il est réalisé de manière intense et inhabituelle, l’exercice excentrique peut entraîner diverses altérations de l’ultrastructure musculaire qui se manifestent par une série de symptômes cliniques comme des douleurs musculaires d’apparition retardées (Delayed-Onset Muscle Soreness, DOMS) et une altération de la fonction musculaire. Malgré la littérature abondante consacrée à la description du phénomène des DOMS, aucune théorie cohérente n’est actuellement disponible pour expliquer la survenue différée des sensations douloureuses et des signes associés. De même, toujours à l’analyse de la littérature, on ne peut que constater l’absence de solution thérapeutique susceptible d’atténuer significativement l’intensité des DOMS et de leurs conséquences fonctionnelles associées à l’exception, paradoxalement, de l’exercice excentrique lui-même qui, lorsqu’il est proposé en conditions sous-maximales d’intensité progressivement croissante, semble constituer la seule prévention réellement efficace de l’apparition des DOMS. De même, si l’efficacité d’un entraînement spécifique dans la prévention des DOMS a été confirmée par de nombreux travaux, la nature de cet effet protecteur reste sujette à conjectures. Nous sommes néanmoins convaincus qu’une meilleure compréhension des réponses aiguës et/ou adaptatives à l’exercice excentrique contribuerait d’une part, à la mise au point d’interventions thérapeutiques efficaces et d’autre part, à élucider les évènements moléculaires impliqués dans des conditions pathologiques telles que les myalgies et certaines maladies neuromusculaires. [less ▲]

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See detailNeutrophil contribution to spinal cord injury and repair
Neirinckx, Virginie ULg; Coste, Cécile ULg; Franzen, Rachelle ULg et al

in Journal of Neuroinflammation (2014), 11(1),

Spinal cord injuries remain a critical issue in experimental and clinical research nowadays, and it is now well accepted that the immune response and subsequent inflammatory reactions are of significant ... [more ▼]

Spinal cord injuries remain a critical issue in experimental and clinical research nowadays, and it is now well accepted that the immune response and subsequent inflammatory reactions are of significant importance in regulating the damage/repair balance after injury. The role of macrophages in such nervous system lesions now becomes clearer and their contribution in the wound healing process has been largely described in the last few years. Conversely, the contribution of neutrophils has traditionally been considered as detrimental and unfavorable to proper tissue regeneration, even if there are very few studies available on their precise impact in spinal cord lesions. Indeed, recent data show that neutrophils are required for promoting functional recovery after spinal cord trauma. In this review, we gathered recent evidence concerning the role of neutrophils in spinal cord injuries but also in some other neurological diseases, highlighting the need for further understanding the different mechanisms involved in spinal cord injury and repair. [less ▲]

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See detailMolecular adaptations in mouse skeletal muscle following eccentrically versus concentrically biased training
Hody, Stéphanie ULg; Lacrosse, Zoé ULg; Simonet, Arnaud et al

Poster (2014, July 02)

Introduction The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human ... [more ▼]

Introduction The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human quadriceps elicited proteome modifications that suggest a muscle fiber typology adaptation (Hody et al. 2011). We address this question in a more systematic way by examining the effects of different running modes on the mouse muscle proteome and the muscle fiber typology on the whole quadriceps. Methods Male adult mice (C57BL6) were randomly divided into downhill running (DHR, quadricipital eccentrically biased contractions), uphill running (UHR, quadricipital concentrically biased contractions) and untrained control (CONT) groups. Running groups performed five training sessions on an inclined treadmill for 75 to 135 min/day and the quadriceps muscles were dissected 96 hours after the last session. Muscle protein extracts of DHR and UHR groups (n=4/group) were subjected to a 2D-DIGE analysis coupled with mass spectrometry. The assessment of fiber type, size and number was performed on the rectus femoris of the three groups (n=6/group) using myosin heavy chain (MHC) immunofluorescence. Results In the proteomic analysis, eight spots identified as the fast MHC isoforms exhibited a lower abundance in DHR compared to UHR (p<0.05, t-test). In contrast, ATP synthase subunit a and tubulin ß were more expressed in DHR (p<0.05). Immunohistological analysis revealed a significant higher proportion of type I and IIa fibers for DHR compared to UHR or CONT groups (p<0.05, one-way ANOVA). Discussion Our data demonstrate that the eccentrically biased contractions in mice induced specific adaptations in protein expression as well as in muscle fiber type and size which may reflect a more oxidative muscle phenotype. The differences in stress placed on the muscle between both trainings may be responsible for some unique adaptations resulting from the eccentrically biased training. Eccentric training is known to protect skeletal muscles against exercise-induced muscle damage (EIMD) which may occur after intense eccentric contractions (Chen et al. 2010; Hody et al. 2011). It is also suggested that fast glycolytic muscle fibers are more vulnerable to EIMD than oxidative fibers (Lieber and Friden, 1988). Therefore, it would be interesting to investigate whether the molecular changes induced by an eccentrically biased training are involved in protection against EIMD. References Chen TC, Chen HL, Lin MJ, Wu CJ, Nosaka K. (2010). Med Sci Sports Exerc 42, 1004-1012. Hody S, Leprince P, Sergeant K, Renaut J, Croisier JL, Wang F, Rogister B. (2011). Med Sci Sports Exerc 43, 2281-2296. Lieber RL, Friden J. (1988). Acta Physiol Scand 133, 587-588. [less ▲]

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See detailThe small Heat Shock Proteins (HSPs) response following eccentric exercise
Hody, Stéphanie ULg; Simonet, Arnaud; Lacrosse, Zoé ULg et al

in Abstract Book GIGA Day 2014 (2014, January 27)

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See detailBone marrow stromal stem cells transplantation in mice with acute spinal cord injury
Neirinckx, Virginie ULg; Rogister, Bernard ULg; Franzen, Rachelle ULg et al

in Methods in Molecular Biology (Clifton, N.J.) (2014), 1213

Spinal cord injured experimental animals are widely used for studying pathophysiological processes after central nervous system acute traumatic lesion and elaborating therapeutic solutions, some of them ... [more ▼]

Spinal cord injured experimental animals are widely used for studying pathophysiological processes after central nervous system acute traumatic lesion and elaborating therapeutic solutions, some of them based on stem cell transplantation. Here, we describe a protocol of spinal cord contusion in C57BL/6J mice, directly followed by bone marrow stromal stem cells transplantation. This model allows for the characterization of neuroprotective and neurorestorative abilities of these stem cells in a context of spinal cord trauma. [less ▲]

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See detailIsocinétisme et douleurs musculaires d’apparition retardée
Hody, Stéphanie ULg; ROGISTER, Bernard ULg; Leprince, Pierre ULg et al

in Movement & Sport Sciences - Science & Motricité (2014), 85(3), 109-119

The curative and preventive efficiency of the isokinetic exercise, especially of the eccentric contraction, has been well demonstrated. However, intense or unusual eccentric exercise is known to induce ... [more ▼]

The curative and preventive efficiency of the isokinetic exercise, especially of the eccentric contraction, has been well demonstrated. However, intense or unusual eccentric exercise is known to induce muscle damage associated with delayed-onset muscle soreness (DOMS) and prolonged functional deficits. These negative consequences can frequently disturb the progress of re-education or training programmes. Since they can affect athletic performance and increase the risk of musculo-skeletal injuries, the structuro-functional alterations associated with DOMS may also be problematic in athletes. Therefore, to optimize the benefits of the eccentric work while avoiding muscle damage and occurrence of DOMS should represent a major objective for the practitioners. To date, the only systematic intervention that brings muscle protection against DOMS consists of performing repeated eccentric sessions at submaximal intensity. Besides its clinical use, isokinetic constitutes an interesting model to generate and investigate the DOMS phenomenon. The original association of eccentric injuring protocols with new emerging techniques of molecular biology appears to be a promising strategy to better understand the cellular and molecular mechanisms underlying exercise-induced muscle damage. Such data would provide better guidelines for prevention or treatment practice. [less ▲]

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See detailAdult mouse subventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling.
Goffart, Nicolas; KROONEN, Jérôme ULg; Di Valentin, Emmanuel ULg et al

in Neuro-oncology (2014)

BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from ... [more ▼]

BACKGROUND: Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months. This catastrophic survival rate is the consequence of systematic relapses that could arise from remaining glioblastoma stem cells (GSCs) left behind after surgery. We previously demonstrated that GSCs are able to escape the tumor mass and specifically colonize the adult subventricular zones (SVZs) after transplantation. This specific localization, away from the initial injection site, therefore represents a high-quality model of a clinical obstacle to therapy and relapses because GSCs notably retain the ability to form secondary tumors. METHOD: In this work, we questioned the role of the CXCL12/CXCR4 signaling in the GSC-specific invasion of the SVZs. RESULTS: We demonstrated that both receptor and ligand are respectively expressed by different GBM cell populations and by the SVZ itself. In vitro migration bio-assays highlighted that human U87MG GSCs isolated from the SVZs (U87MG-SVZ) display stronger migratory abilities in response to recombinant CXCL12 and/or SVZ-conditioned medium (SVZ-CM) compared with cancer cells isolated from the tumor mass (U87MG-TM). Moreover, in vitro inhibition of the CXCR4 signaling significantly decreased the U87MG-SVZ cell migration in response to the SVZ-CM. Very interestingly, treating U87MG-xenografted mice with daily doses of AMD3100, a specific CXCR4 antagonist, prevented the specific invasion of the SVZ. Another in vivo experiment, using CXCR4-invalidated GBM cells, displayed similar results. CONCLUSION: Taken together, these data demonstrate the significant role of the CXCL12/CXCR4 signaling in this original model of brain cancer invasion. [less ▲]

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See detailExpression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis
CREVECOEUR, Julie ULg; Kaminski, RM; Rogister, Bernard ULg et al

in Neuropathology & Applied Neurobiology (2014), 40(2), 191-204

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See detailSpinal Cord Injuries – How Could Adult Mesenchymal and Neural Crest Stem Cells Take Up the Challenge?
Neirinckx, Virginie ULg; CANTINIEAUX, Dorothée ULg; Coste, Cécile ULg et al

in Stem Cells (2013)

Since several years, adult/perinatal mesenchymal and neural crest stem cells have been widely used to help experimental animal to recover from spinal cord injury. More interestingly, recent clinical ... [more ▼]

Since several years, adult/perinatal mesenchymal and neural crest stem cells have been widely used to help experimental animal to recover from spinal cord injury. More interestingly, recent clinical trials confirmed the beneficial effect of those stem cells, which improve functional score of patients suffering from such lesions. However, a complete understanding of the mechanisms of stem cell-induced recovery is seriously lacking. Indeed, spinal cord injuries gathered a wide range of biochemical and physiopathological events (such as inflammation, oxidative stress, axonal damage, demyelination, etc) and the genuine healing process after cell transplantation is not sufficiently defined. This review aims to sum up recent data about cell therapy in spinal cord lesions using mesenchymal or recently identified neural crest stem cells, by describing precisely which physiopathological parameter is affected and the exact processes underlying the observed changes. Overall, although significant advances are acknowledged, it seems that further deep mechanistic investigation is needed for the development of optimized and efficient cell-based therapy protocols. [less ▲]

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See detailProteomic study of lumbar spinal cord after quadricipital eccentric exercise
Lacrosse, Zoé ULg; Hody, Stéphanie ULg; Leprince, Pierre ULg et al

Poster (2013, September 12)

Eccentric muscle contractions are characterized by an increase of muscle tension as it lengthens (slowering movements). Unaccustomed or intense eccentric exercise causes “Delayed-Onset Muscle Soreness” ... [more ▼]

Eccentric muscle contractions are characterized by an increase of muscle tension as it lengthens (slowering movements). Unaccustomed or intense eccentric exercise causes “Delayed-Onset Muscle Soreness” (DOMS). DOMS include muscle pain that appears 24 to 72 hours after exercise, but also stiffness, edema and muscle proteins release in plasma as a hallmark of muscle fibers injuries. The only systematic intervention that brings a muscle protection against DOMS is to realize submaximal eccentric contractions with a progressively increased intensity. The mechanism of this protection, called the “Repeated Bout Effect” (RBE), is not understood. However, it is likely explained by cellular, mechanical and neural theories [Scand.J.Med.&Sci.Sports, 13, 88, 2003]. The objective of this study is to better understand which neural signal is released in the muscle synapse and which brings protection by RBE. Male adult mice (C57BL6) were randomly divided into downhill running (DHR), uphill running (UHR) and untrained control (CONT) groups (n=4/group). DHR group is characterized by eccentric contractions of the quadriceps while UHR is concerned by concentric contractions. Running groups performed a warm-up of ten minutes followed by an interval exercise on an inclined treadmill at a velocity of 20cm/s. The latter consisted of running 18 bouts of 5 minutes interspersed with a 2 minutes rest. Lumbar spinal cord was dissected 24h after the race. Nuclear and cytoplasmic proteins were separately extracted and subjected to a 2D-DIGE analysis coupled with mass spectrometry. We do not observe any cytoplasmic protein modification while in the nuclear extract, seven spots were more abundant in eccentric group and four in concentric group in comparison with control group. The mass spectrometry of these proteins reveals that they are implicated in axoplasmic transport. At 24 hours, too few proteins modifications were detected in lumbar spinal cord, maybe as a consequence of a too short period between race and euthanasia. Implication of axoplasmic transport comforts our starting hypothesis that nervous system is able to protect muscle during the RBE by a synthesis and then a synaptic release of molecules modifying the muscle physiology. [less ▲]

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See detailProteomic study of lumbar spinal cord after quadricipital eccentric exercise
Lacrosse, Zoé ULg; Lacrosse, Zoé ULg; Hody, Stéphanie ULg et al

in 17th EURON PhD meeting (2013, September)

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See detailThe susceptibility of the knee extensors to eccentric exercise-induced muscle damage is not affected by leg dominance but by exercise order .
Hody, Stéphanie ULg; Rogister, Bernard ULg; Leprince, Pierre ULg et al

in Clinical Physiology & Functional Imaging (2013), 33(5), 373-380

The aims of this study were first to compare the response of dominant and non-dominant legs to eccentric exercise and second, to examine whether there is an effect of exercise order on the magnitude of ... [more ▼]

The aims of this study were first to compare the response of dominant and non-dominant legs to eccentric exercise and second, to examine whether there is an effect of exercise order on the magnitude of symptoms associated with intense eccentric protocols. Eighteen young men performed 3 sets of 30 maximal eccentric isokinetic (60°.sec-1) contractions of the knee extensors (range of motion, ROM: 0°-100°, 0=full extension) using either dominant or nondominant leg. They repeated a similar eccentric bout using the contralateral leg six weeks later. The sequence of leg’s use was allocated to create equally balanced groups. Four indirect markers of muscle damage including subjective pain intensity, maximal isometric strength, muscle stiffness and plasma CK activity were measured before and 24 hours after exercise. All markers changed significantly following the eccentric bout performed either by dominant or non-dominant legs but no significant difference was observed between legs. Interestingly, the comparison between the first and second eccentric bouts revealed that muscle soreness (-42%, p<0.001), CK activity (-62%, p<0.05) and strength loss (-54%, p<0.01) were significantly lower after the second bout. This study suggests that leg dominance does not influence the magnitude of exercise-induced muscle damage and supports for the first time the existence of a contralateral protection against exercise-induced muscle damage in the lower limbs. [less ▲]

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See detailExpression of SV2 isoforms during rodent brain development
Crevecoeur, Julie; Foerch, P; Doupagne, Mélissa et al

in BMC Neuroscience (2013)

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See detailEffects of eccentrically and concentrically biased training on mouse muscle phenotype
Hody, Stéphanie ULg; Lacrosse, Zoé ULg; Leprince, Pierre ULg et al

in Medicine & Science in Sports & Exercise (2013), 45(8), 1460-1468

Introduction: The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human ... [more ▼]

Introduction: The molecular adaptations specifically induced by different muscle contraction types have only been partially elucidated. We previously demonstrated that eccentric contractions in human quadriceps elicited proteome modifications that suggest a muscle fiber typology adaptation. We address this question in a more systematic way by examining here the effects of different running modes on the mouse muscle proteome and the muscle fiber typology. Methods: Male adult mice (C57BL6) were randomly divided into downhill running (DHR, quadricipital eccentrically biased contractions), uphill running (UHR, quadricipital concentrically biased contractions) and untrained control (CONT) groups. Running groups performed five training sessions on an inclined treadmill for 75 to 135 min/day and the quadriceps muscles were dissected 96hours after the last session. Muscle protein extracts of DHR and UHR groups (n=4/group) were subjected to a 2D-DIGE analysis coupled with mass spectrometry. The assessment of fiber type, size and number was performed on the rectus femoris of the three groups (n=6/group) using myosin heavy chain (MHC) immunohistochemistry. Results: In the proteomic analysis, eight spots identified as the fast MHC isoforms exhibited a lower abundance in DHR compared to UHR (p<0.05, t-test). In contrast, ATP synthase subunit α and tubulin β were more expressed in DHR (p<0.05). A significant higher proportion of type I and IIa fibers was found for DHR compared to UHR or CONT groups (p<0.05, one-way ANOVA). Conclusions: Our data suggest that the eccentrically biased contractions in mice induced specific adaptations in protein expression and muscle fiber composition which may reflect a more oxidative muscle phenotype. The differences in stress placed on the muscle between both trainings may be responsible for some unique adaptations resulting from the eccentrically biased training. [less ▲]

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See detailMuscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response
Hody, Stéphanie ULg; Rogister, Bernard ULg; Leprince, Pierre ULg et al

in Scandinavian Journal of Medicine & Science in Sports (2013), 23(4), 501-7

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized ... [more ▼]

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large intersubject variability was observed for all criteria measured. More interestingly, the log (CKpost/CKpre) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r2 = 0.70 and r = 0.75, r2 = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans. [less ▲]

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See detailIn vitro and in vivo Characterization of Adult Bone Marrow Neural Crest Stem Cells
Coste, Cécile ULg; Neirinckx, Virginie ULg; Manguette, Jérôme et al

Poster (2013, May 31)

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See detailAdult Bone Marrow Neural Crest Stem Cells and Mesenchymal Stem Cells are not able to Replace Lost Neurons in Acute MPTP-lesioned Mice
Neirinckx, Virginie ULg; Marquet, Alice ULg; Coste, Cécile ULg et al

in PLoS ONE (2013), 8(5),

Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage ... [more ▼]

Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC) or mesenchymal stem cells (MSC) survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management. [less ▲]

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