Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation

Vienna, Austria

Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation

Vienna, Austria
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Carnio S.,Venetian Institute of Molecular Medicine | LoVerso F.,Venetian Institute of Molecular Medicine | Baraibar M.,University Pierre and Marie Curie | Longa E.,University of Pavia | And 17 more authors.
Cell Reports | Year: 2014

The cellular basis of age-related tissue deterioration remains largely obscure. The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. Autophagy is activated both under short and prolonged stress and is required to clear the cell of dysfunctional organelles and altered proteins. We report that specific autophagy inhibition in muscle has a major impact on neuromuscular synaptic function and, consequently, on muscle strength, ultimately affecting the lifespan of animals. Inhibition of autophagy also exacerbates aging phenotypes in muscle, such as mitochondrial dysfunction, oxidative stress, and profound weakness. Mitochondrial dysfunction and oxidative stress directly affect acto-myosin interaction and force generation but show a limited effect on stability of neuromuscular synapses. These results demonstrate that age-related deterioration of synaptic structure and function is exacerbated by defective autophagy. © 2014 The Authors.


PubMed | Venetian Institute of Molecular Medicine, Medical University of Vienna, University of Primorska, Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation and Comenius University
Type: Journal Article | Journal: European journal of translational myology | Year: 2016

Sarcopenia is the age-related loss of muscle mass and function, reducing force generation and mobility in the elderlies. Contributing factors include a severe decrease in both myofiber size and number as well as a decrease in the number of motor neurons innervating muscle fibers (mainly of fast type) which is sometimes accompanied by reinnervation of surviving slow type motor neurons (motor unit remodeling). Reduced mobility and functional limitations characterizing aging can promote a more sedentary lifestyle for older individuals, leading to a vicious circle further worsening muscle performance and the patients quality of life, predisposing them to an increased risk of disability, and mortality. Several longitudinal studies have shown that regular exercise may extend life expectancy and reduce morbidity in aging people. Based on these findings, the Interreg IVa project aimed to recruit sedentary seniors with a normal life style and to train them for 9 weeks with either leg press (LP) exercise or electrical stimulation (ES). Before and at the end of both training periods, all the subjects were submitted to mobility functional tests and muscle biopsies from the Vastus Lateralis muscles of both legs. No signs of muscle damage and/or of inflammation were observed in muscle biopsies after the training. Functional tests showed that both LP and ES induced improvements of force and mobility of the trained subjects. Morphometrical and immunofluorescent analyses performed on muscle biopsies showed that ES significantly increased the size of fast type muscle fibers (p<0.001), together with a significant increase in the number of Pax7 and NCAM positive satellite cells (p<0.005). A significant decrease of slow type fiber diameter was observed in both ES and LP trained subjects (p<0.001). Altogether these results demonstrate the effectiveness of physical exercise either voluntary (LP) or passive (ES) to improve the functional performances of aging muscles. Here ES is demonstrated to be a safe home-based method to counteract fast type fiber atrophy, typically associated with aging skeletal muscle.


PubMed | University of Padua, Vienna University of Technology, University of Primorska, University of Chieti Pescara and 5 more.
Type: Journal Article | Journal: Physiological reports | Year: 2016

Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca


PubMed | University of Padua, Reykjavik University, University of Chieti Pescara, Foundation San Camillo Hospital and 3 more.
Type: Journal Article | Journal: European journal of translational myology | Year: 2016

Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI) patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES). Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb). Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest that the MHCemb positive muscle fibers we observe result from the activation, proliferation and fusion of satellite cells, the myogenic precursors present under the basal lamina of the muscle fibers. Using morphological features and molecular biomarkers, we show that severely atrophic muscle fibers, with a peculiar cluster reorganization of myonuclei, are present in rodent muscle seven-months after neurectomy and in human muscles 30-months after complete Conus-Cauda Equina Syndrome and that these are structurally distinct from early myotubes. Beyond reviewing evidence from rodent and human studies, we add some ultrastructural evidence of muscle fiber regeneration in long-term denervated human muscles and discuss the options to substantially increase the regenerative potential of severely denervated human muscles not having been treated with h-bFES. Some of the mandatory procedures, are ready to be translated from animal experiments to clinical studies to meet the needs of persons with long-term irreversible muscle denervation. An European Project, the trial Rise4EU (Rise for You, a personalized treatment for recovery of function of denervated muscle in long-term stable SCI) will hopefully follow.


Sarabon N.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation | Sarabon N.,University of Primorska | Rosker J.,University of Primorska | Loefler S.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation | Kern H.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation
Gait and Posture | Year: 2013

Literature confirms the effects of vision and stance on body sway and indicates possible interactions between the two. However, no attempts have been made to systematically compare the effect of vision on the different types of stance which are frequently used in clinical and research practice. The biomechanical changes that occur after changing shape and size of the support surface suggest possible sensory re-weighting might take place. The purpose of this study was to assess the effect of vision on body sway in relation to different stance configurations and width. Thirty-eight volunteers performed four quiet stance configurations (parallel, semi-tandem, tandem and single leg), repeating them with open and closed eyes. Traditional parameters, recurrence quantification analysis and sample entropy were analyzed from the CoP trajectory signal. Traditional and recurrence quantification analysis parameters were affected by vision removal and stance type. Exceptions were frequency of oscillation, entropy and trapping time. The most prominent effect of vision elimination on traditional parameters was observed for narrower stances. A significant interaction effect between vision removal and stance type was present for most of the parameters observed ( p<. 0.05). The interaction effect between medio-lateral and antero-posterior traditional parameters differed in linearity between stances. The results confirm the effect of vision removal on the body sway. However, for the medio-lateral traditional parameters, the effects did not increase linearly with the change in width and stance type. This suggests that removal of vision could be more effectively compensated by other sensory systems in semi-tandem stance, tandem and single legged stance. © 2013 Elsevier B.V.


Nejc S.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation | Nejc S.,University of Primorska | Jernej R.,Prevention and Rehabilitation Sports Center | Loefler S.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation | Kern H.,Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation
Journal of Sports Science and Medicine | Year: 2010

The centre of pressure (COP) movement during stance maintenance on a stable surface is commonly used to describe and evaluate static balance. The aim of our study was to test sensitivity of individual COP parameters to different stance positions which were used to address size specific changes in the support surface. Twenty-nine subjects participated in the study. They carried out three 60-second repetitions of each of the five balance tasks (parallel stance, semi-tandem stance, tandem stance, contra-tandem stance, single leg stance). Using the force plate, the monitored parameters included the total COP distance, the distance covered in anteroposterior and mediolateral directions, the maximum oscillation amplitude in anteroposterior and mediolateral directions, the total frequency of oscillation, as well as the frequency of oscillation in anteroposterior and mediolateral directions. The parameters which describe the total COP distance were the most sensitive to changes in the balance task, whereas the frequency of oscillation proved to be sensitive to a slightly lesser extent. Reductions in the support surface size in each of the directions resulted in proportional changes of antero-posterior and mediolateral directions. The frequency of oscillation did not increase evenly with the increase in the level of difficulty of the balance task, but reached a certain value, above which it did not increase. Our study revealed the monitored parameters of the COP to be sensitive to the support surface size manipulations. The results of the study provide an important source for clinical and research use of the body sway measurements. © Journal of Sports Science and Medicine.


PubMed | IRCCS Fondazione Ospedale San Camillo, University of Padua and Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation
Type: Journal Article | Journal: European journal of translational myology | Year: 2017

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active, i.e., on the slow motoneurons. The preferential reinnervation that follows along decades of increased activity maintains neuron and myofibers. All together the results open interesting perspectives for applications of FES and electroceuticals for rejuvenation of aged muscles to delay functional decline and loss of independence that are unavoidable burdens of advanced aging.ClinicalTrials.gov: NCT01679977.


PubMed | University of Padua, San Camillo Hospital Irccs, Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation and Southern Illinois University Carbondale
Type: Journal Article | Journal: European journal of translational myology | Year: 2016

This work reviews history, current clinical relevance and future of fibrillation, a functional marker of skeletal muscle denervated fibers. Fibrillations, i.e., spontaneous contraction, in denervated muscle were first described during the nineteenth century. It is known that alterations in membrane potential are responsible for the phenomenon and that they are related to changes in electrophysiological factors, cellular metabolism, cell turnover and gene expression. They are known to inhibit muscle atrophy to some degree and are used to diagnose neural injury and reinnervation that are occurring in patients. Electromyography (EMG) is useful in determining progress, prognosis and efficacy of therapeutic interventions and their eventual change. For patients with peripheral nerve injury, and thus without the option of volitional contractions, electrical muscle stimulation may be helpful in preserving the contractility and extensibility of denervated muscle tissue and in retarding/counteracting muscle atrophy. It is obvious from the paucity of recent literature that research in this area has declined over the years. This is likely a consequence of the decrease in funding available for research and the fact that the fibrillations do not appear to cause serious health issues. Nonetheless, further exploration of them as diagnostic tools in long-term denervation is merited, in particular if Single Fiber EMG (SFEMG) is combined with Dynamic Echomyography (DyEM), an Ultra Sound muscle approach we recently designed and developed to explore denervated and reinnervating muscles.


PubMed | University of Padua, IRRCS Fondazione Ospedale San Camillo, Institute of Physical Medicine and Rehabilitation, Institute for Biomedical and Neural Engineering and 4 more.
Type: Journal Article | Journal: European journal of translational myology | Year: 2016

There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI) sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it should be possible to defer the muscle decline that occurs in aging people and in those who have become unable to participate in physical activities. Thus, FES should be considered for use in rehabilitation centers, nursing facilities and in critical care units when patients are completely inactive even for short periods of time.

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