scholarly journals Biology of muscle atrophy and of its recovery by FES in aging and mobility impairments: roots and by-products

2015 ◽  
Vol 25 (4) ◽  
pp. 221 ◽  
Author(s):  
Ugo Carraro ◽  
Helmut Kern ◽  
Paolo Gava ◽  
Christian Hofer ◽  
Stefan Loefler ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Strong Evidence ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Cauda Equina ◽  
Complete Disappearance ◽  
Muscle Adaptation ◽  
Irreversible Damage ◽  
Cord Injury ◽  
Muscle Biopsies

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 <em>Conus</em> and <em>Cauda Equina</em>, 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.

scholarly journals Two years of Functional Electrical Stimulation by large surface electrodes for denervated muscles improve skin epidermis in SCI

2018 ◽  
Vol 28 (1) ◽  
Author(s):  
Giovanna Albertin ◽  
Helmut Kern ◽  
Christian Hofer ◽  
Diego Guidolin ◽  
Andrea Porzionato ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Functional Electrical Stimulation ◽  
Muscle Fibers ◽  
Cauda Equina ◽  
Skin Thickness ◽  
Surface Electrodes ◽  
Long Term Treatment ◽  
Cord Injury ◽  
Skin Biopsies

Our previous studies have shown that severely atrophic Quadriceps muscles of spinal cord injury (SCI) patients suffering with complete conus and cauda equina lesions, and thus with permanent denervation-induced atrophy and degeneration of muscle fibers, were almost completely rescued to normal size after two years of home-based Functional Electrical Stimulation (h-bFES). Since we used large surface electrodes to stimulate the thigh muscles, we wanted to know if the skin was affected by long-term treatment. Here we report preliminary data of morphometry of skin biopsies harvested from legs of 3 SCI patients before and after two years of h-bFES to determine the total area of epidermis in transverse skin sections. By this approach we support our recently published results obtained randomly measuring skin thickness in the same biopsies after H-E stain. The skin biopsies data of three subjects, taken together, present indeed a statistically significant 30% increase in the area of the epidermis after two years of h-bFES. In conclusion, we confirm a long term positive modulation of electrostimulated epidermis, that correlates with the impressive improvements of the FES-induced muscle strength and bulk, and of the size of the muscle fibers after 2-years of h-bFES.

scholarly journals Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers

2001 ◽  
Vol 155 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Yewei Liu ◽  
Zoltán Cseresnyés ◽  
William R. Randall ◽  
Martin F. Schneider
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Nuclear Translocation ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Adult Skeletal Muscle ◽  
Skeletal Muscle Fibers ◽  
Slow Twitch ◽  
Nuclear Foci ◽  
Fast Twitch

TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2) may contribute to slow-twitch skeletal muscle fiber type–specific gene expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either wild-type or constitutively active mutant NFATc [NFATc(S→A)] were expressed in cultured adult mouse skeletal muscle fibers from flexor digitorum brevis (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S→A) exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers expressing NFATc–GFP, fluorescence was localized at the sarcomeric z-lines and absent from nuclei. Electrical stimulation using activity patterns typical of slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every 50 s, caused cyclosporin A–sensitive appearance of fluorescent foci of NFATc–GFP in all nuclei. Fluorescence of nuclear foci increased during the first hour of stimulation and then remained constant during a second hour of stimulation. Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc–GFP without electrical stimulation. Nuclear translocation of NFATc–GFP did not occur with either continuous 1 Hz stimulation or with the fast-twitch fiber activity pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern–dependent nuclear translocation of NFATc demonstrated here could thus contribute to fast-twitch to slow-twitch fiber type transformation.

scholarly journals Home-Based Functional Electrical Stimulation of Human Permanent Denervated Muscles: A Narrative Review on Diagnostics, Managements, Results and Byproducts Revisited 2020

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 529 ◽  
Author(s):  
Helmut Kern ◽  
Ugo Carraro
Keyword(s):  
Electrical Stimulation ◽  
Functional Electrical Stimulation ◽  
Cauda Equina ◽  
Quadriceps Muscle ◽  
Ultrastructural Organization ◽  
Force Output ◽  
Case Scenario ◽  
Worst Case ◽  
Home Based ◽  
Cord Injury

Spinal cord injury (SCI) produces muscle wasting that is especially severe after complete and permanent damage of lower motor neurons, as can occur in complete conus and cauda equina syndrome. Even in this worst-case scenario, mass and function of permanently denervated quadriceps muscle can be rescued by surface functional electrical stimulation using a purpose designed home-based rehabilitation strategy. Early diagnostics is a key factor in the long-term success of this management. Function of quadriceps muscle was quantitated by force measurements. Muscle gross cross-sections were evaluated by quantitative color computed tomography (CT) and muscle and skin biopsies by quantitative histology, electron microscopy, and immunohistochemistry. Two years of treatment that started earlier than 5 years from SCI produced: (a) an increase in cross-sectional area of stimulated muscles; (b) an increase in muscle fiber mean diameter; (c) improvements in ultrastructural organization; and (d) increased force output during electrical stimulation. Improvements are extended to hamstring muscles and skin. Indeed, the cushioning effect provided by recovered tissues is a major clinical benefit. It is our hope that new trials start soon, providing patients the benefits they need.

scholarly journals Physical exercise in Aging: Nine weeks of leg press or electrical stimulation training in 70 years old sedentary elderly people

2015 ◽  
Vol 25 (4) ◽  
pp. 237 ◽  
Author(s):  
Sandra Zampieri ◽  
Simone Mosole ◽  
Stefan Löfler ◽  
Hannah Fruhmann ◽  
Samantha Burggraf ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Physical Exercise ◽  
Motor Neurons ◽  
Muscle Fibers ◽  
Functional Tests ◽  
Trained Subjects ◽  
Leg Press ◽  
Slow Type ◽  
Muscle Biopsies ◽  
Type Fiber

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&lt;0.001), together with a significant increase in the number of Pax7 and NCAM positive satellite cells (p&lt;0.005). A significant decrease of slow type fiber diameter was observed in both ES and LP trained subjects (p&lt;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.

scholarly journals Severely atrophic human muscle fibers with nuclear misplacement survive many years of permanent denervation

2016 ◽  
Vol 26 (2) ◽  
Author(s):  
Ugo Carraro ◽  
Helmut Kern
Keyword(s):  
Muscle Fibers ◽  
Human Muscle ◽  
Slow Muscle ◽  
Denervated Muscle ◽  
Cord Injury ◽  
Atrophic Muscle ◽  
Complete Spinal Cord Injury ◽  
Muscle Biopsies ◽  
Immunohistochemical Analyses

Likewise in rodents, after complete spinal cord injury (SCI) the lower motor neuron (LMN) denervated human muscle fibers lose completely the myofibrillar apparatus and the coil distribution of myonuclei that are relocated in groups (nuclear clumps) in the center of severely atrophic muscle fibers. Up to two years of LMN denervation the muscle fibers with nuclear clumps are very seldom, but in this cohort of patients the severely atrophic muscle fibers are frequent in muscle biopsies harvested three to six years after SCI. Indeed, the percentage increased to 27 ± 9% (p&lt; 0.001), and then abruptly decreased from the 6th year onward, when fibrosis takes over to neurogenic muscle atrophy. Immunohistochemical analyses shown that nuclear misplacements occurred in both fast and slow muscle fibers. In conclusion, human muscle fibers survive permanent denervation much longer than generally accepted and relocation of nuclei is a general behavior in long term denervated muscle fibers.

scholarly journals Functional electrical stimulation of permanently denervated muscles, updated 2020

2020 ◽  
Vol 97 (3) ◽  
pp. 130-136 ◽  
Author(s):  
U. Carraro ◽  
H. Kern ◽  
G. Albertin G. ◽  
S. Masiero ◽  
A. Pond ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Functional Electrical Stimulation ◽  
Cauda Equina ◽  
Quadriceps Muscle ◽  
Ultrastructural Organization ◽  
Force Output ◽  
Case Scenario ◽  
Cross Sectional ◽  
Worst Case ◽  
Cord Injury

Spinal cord injury produces muscle wasting, which is especially severe after the complete and permanent damage of lower motor neurons that occurs in complete Cauda Equina Syndrome. Even in this worst-case scenario, we have shown that permanently denervated Quadriceps muscle can be rescued by surface Functional Electrical Stimulation and a purpose designed home-based rehabilitation regime. Here, our aim is to show that the effects are extended to both antagonist muscles and the skin of the thighs. Before and after 2 years of electrical stimulation, mass and structure of Quadriceps and Hamstrings muscles were quantitated by force measurements. Muscle gross cross section were evaluated using color computed tomography, muscle and skin biopsies by quantitative histology and immunohistochemistry. The treatment produced: a) an increase in cross-sectional area of stimulated muscles; b) an increase in muscle fiber mean diameter; c) improvements in ultrastructural organization; and d) increased force output during electrical stimulation. The recovery of Quadriceps muscle force was sufficient to allow 25% of the compliant subjects to perform stand-up and step-in place trainings. Improvements are extended to hamstring muscles and skin. Indeed, the cushioning effect provided by recovered tissues is a major clinical benefit. It is our hope that, with or without our advice, trials may start soon in Europe and Russia to provide persons-in-need the help they deserve.

scholarly journals Deep muscle-proteomic analysis of freeze-dried human muscle biopsies reveals fiber type-specific adaptations to exercise training

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. S. Deshmukh ◽  
D. E. Steenberg ◽  
M. Hostrup ◽  
J. B. Birk ◽  
J. K. Larsen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Fiber Type ◽  
Muscle Fibers ◽  
Human Muscle ◽  
Fiber Types ◽  
Freeze Dried ◽  
Fast Twitch Muscle ◽  
Fast Twitch ◽  
Muscle Biopsies

AbstractSkeletal muscle conveys several of the health-promoting effects of exercise; yet the underlying mechanisms are not fully elucidated. Studying skeletal muscle is challenging due to its different fiber types and the presence of non-muscle cells. This can be circumvented by isolation of single muscle fibers. Here, we develop a workflow enabling proteomics analysis of pools of isolated muscle fibers from freeze-dried human muscle biopsies. We identify more than 4000 proteins in slow- and fast-twitch muscle fibers. Exercise training alters expression of 237 and 172 proteins in slow- and fast-twitch muscle fibers, respectively. Interestingly, expression levels of secreted proteins and proteins involved in transcription, mitochondrial metabolism, Ca2+ signaling, and fat and glucose metabolism adapts to training in a fiber type-specific manner. Our data provide a resource to elucidate molecular mechanisms underlying muscle function and health, and our workflow allows fiber type-specific proteomic analyses of snap-frozen non-embedded human muscle biopsies.

scholarly journals Myokines in Home-Based Functional Electrical Stimulation-Induced Recovery of Skeletal Muscle in Elderly and Permanent Denervation

2018 ◽  
Vol 28 (4) ◽  
Author(s):  
Sascha Sajer ◽  
Giulio Sauro Guardiero ◽  
Bianca Maria Scicchitano
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Muscle Atrophy ◽  
Functional Electrical Stimulation ◽  
Neuromuscular Disorders ◽  
Muscle Fibers ◽  
Home Based ◽  
Cord Injury

Neuromuscular disorders, disuse, inadequate nutrition, metabolic diseases, cancer and aging produce muscle atrophy and this implies that there are different types of molecular triggers and signaling pathways for muscle wasting. Exercise and muscle contractions may counteract muscle atrophy by releasing a group of peptides, termed myokines, to protect the functionality and to enhance the exercise capacity of skeletal muscle. In this review, we are looking at the role of myokines in the recovery of permanent denervated and elderly skeletal muscle tissue. Since sub-clinical denervation events contribute to both atrophy and the decreased contractile speed of aged muscle, we saw a parallel to spinal cord injury and decided to look at both groups together. The muscle from lifelong active seniors has more muscle bulk and more slow fiber-type groupings than those of sedentary seniors, demonstrating that physical activity maintains slow motoneurons that reinnervate the transiently denervated muscle fibers. Furthermore, we summarized the evidence that muscle degeneration occur with irreversible Conus and Cauda Equina syndrome, a spinal cord injury in which the human leg muscles may be permanently disconnected from the peripheral nervous system. In these patients, suffering with an estreme case of muscle disuse, a complete loss of muscle fibers occurs within five to ten years after injury. Their recovered tetanic contractility, induced by home-based Functional Electrical Stimulation, can restore the muscle size and function in compliant Spinal Cord Injury patients, allowing them to perform electrical stimulation-supported stand-up training. Myokines are produced and released by muscle fibers under contraction and exert both local and systemic effects. Changes in patterns of myokine secretion, particularly of IGF-1 isoforms, occur in long-term Spinal Cord Injury persons and also in very aged people. Their modulation in Spinal Cord Injury and late aging are also key factors of home-based Functional Electrical Stimulation - mediated muscle recovery. Thus, Functional Electrical Stimulation should be prescribed in critical care units and nursing facilities, if persons are unable or reluctant to exercise. This will result in less frequent hospitalizations and a reduced burden on patients’ families and public health services.

Home-Based Functional Electrical Stimulation Rescues Permanently Denervated Muscles in Paraplegic Patients With Complete Lower Motor Neuron Lesion

2010 ◽  
Vol 24 (8) ◽  
pp. 709-721 ◽  
Author(s):  
Helmut Kern ◽  
Ugo Carraro ◽  
Nicoletta Adami ◽  
Donatella Biral ◽  
Christian Hofer ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Muscle Mass ◽  
Functional Electrical Stimulation ◽  
Cauda Equina ◽  
Ultrastructural Organization ◽  
Mass Force ◽  
Cross Sectional ◽  
Home Based ◽  
Cord Injury ◽  
Denervated Muscles

Background. Spinal cord injury causes muscle wasting and loss of function, which are especially severe after complete and permanent damage to lower motor neurons. In a previous cross-sectional study, long-standing denervated muscles were rescued by home-based functional electrical stimulation (h-bFES) training. Objective. To confirm results by a 2-year longitudinal prospective study of 25 patients with complete conus/cauda equina lesions. Methods. Denervated leg muscles were stimulated by h-bFES using a custom-designed stimulator and large surface electrodes. Muscle mass, force, and structure were determined before and after 2 years of h-bFES using computed tomography, measurements of knee torque during stimulation, and muscle biopsies analyzed by histology and electron microscopy. Results. Twenty of 25 patients completed the 2-year h-bFES program, which resulted in ( a) a 35% cross-sectional increase in area of the quadriceps muscle from 28.2 ± 8.1 to 38.1 ± 12.7 cm 2 ( P < .001), a 75% increase in mean diameter of muscle fibers from 16.6 ± 14.3 to 29.1 ± 23.3 μm ( P < .001), and improvements of the ultrastructural organization of contractile material; and ( b) a 1187% increase in force output during electrical stimulation from 0.8 ± 1.3 to 10.3 ± 8.1 N m ( P < .001). The recovery of quadriceps force was sufficient to allow 25% of the subjects to perform FES-assisted stand-up exercises. Conclusions. Home-based FES of denervated muscle is an effective home therapy that results in rescue of muscle mass and tetanic contractility. Important immediate benefits for the patients are the improved cosmetic appearance of lower extremities and the enhanced cushioning effect for seating.

The “KIMWIPE” Effect in Ultra-Thin Cryosections

1985 ◽  
Vol 43 ◽  
pp. 458-459
Author(s):  
I. Taylor ◽  
P. Ingram ◽  
J.R. Sommer
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Fibers ◽  
Ice Crystals ◽  
Crystal Formation ◽  
Ice Crystal ◽  
Thin Sections ◽  
Skeletal Muscle Fibers ◽  
Freeze Dried ◽  
Ice Crystal Formation

In studying quick-frozen single intact skeletal muscle fibers for structural and microchemical alterations that occur milliseconds, and fractions thereof, after electrical stimulation, we have developed a method to compare, directly, ice crystal formation in freeze-substituted thin sections adjacent to all, and beneath the last, freeze-dried cryosections. We have observed images in the cryosections that to our knowledge have not been published heretofore (Figs.1-4). The main features are that isolated, sometimes large regions of the sections appear hazy and have much less contrast than adjacent regions. Sometimes within the hazy regions there are smaller areas that appear crinkled and have much more contrast. We have also observed that while the hazy areas remain still, the regions of higher contrast visibly contract in the beam, often causing tears in the sections that are clearly not caused by ice crystals (Fig.3, arrows).

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