Academic literature on the topic 'NEURO-MUSCULAR DEGENERATION'

Muscular regeneration is a complex biological process that occurs during acute injury and chronic degeneration, implicating several cell types. One of the earliest events of muscle regeneration is the inflammatory response, followed by the activation and differentiation of muscle progenitor cells. However, the process of novel neuromuscular junction formation during muscle regeneration is still largely unexplored. Here, we identify by single-cell RNA sequencing and isolate a subset of vessel-associated cells able to improve myogenic differentiation. We termed them ‘guide’ cells because of their remarkable ability to improve myogenesis without fusing with the newly formed fibers. In vitro, these cells showed a marked mobility and ability to contact the forming myotubes. We found that these cells are characterized by CD44 and CD34 surface markers and the expression of Ng2 and Ncam2. In addition, in a murine model of acute muscle injury and regeneration, injection of guide cells correlated with increased numbers of newly formed neuromuscular junctions. Thus, we propose that guide cells modulate de novo generation of neuromuscular junctions in regenerating myofibers. Further studies are necessary to investigate the origin of those cells and the extent to which they are required for terminal specification of regenerating myofibers.

Motor neuron diseases (MND) are heterogeneous spectra of disorders that that primarily affect the motor neurons (MN) resulting in motor nerve and muscle degeneration. The pathophysiological mechanisms of MN cell death are known to be combined with disturbance of proteostasis, ribonucleostasis and exaggerated neuro-inflammation. Amyotrophic lateral sclerosis is the prototypic disease of MND followed by spinal and bulbar muscular atrophy, spinal muscular atrophy, benign focal amyotrophy and other various diseases. Although diverse spectra of these diseases share common symptoms, significant differences are known in their clinical manifestations and their clinical progression. With increasing number of new clinical trials, the importance of selecting appropriate clinical scales for the monitoring of clinical progression in different types of MNDs should be emphasized. The purpose of this review is to illustrate different types of clinical scales and demonstrate how to utilize these in the clinical research field with consensus. With these efforts, we hope to be ready to understand different kinds of clinical scales in MND in participating global standard clinical trials.

The temporomandibular joint (TMJ) is a synovial joint that connects the mandibular to the skull. Its main function is to facilitate the movement of the jaw and when it suffers any type of damage or injury, it leads to a decrease in mobility and pain in the area. This localized pain is called temporomandibular joint disorders (TMJD), and it can be caused by intraarticular or extraarticular disorders. The most common symptoms include acute pain, decreased mouth opening, tightening of the muscle, headache, and loss of joint function. Nowadays, there are treatments for temporomandibular joint dysfunction from surgical procedures up to less invasive methods, such as the use of splints. Platelet rich plasma (PRP), hyaluronic acid (HA) and botulinum toxin (BTX) injections have been categorized as a complement of primary treatment in TMJD, as well as decrease drug excess in patients. Due to their natural origin, PRP and HA can regenerate tissue in cases of cartilage degeneration, inhibit inflammation, slow down the progression of osteoarthritis and increase the production of natural lubricating fluid in the joint. Its intra-articular application reduces pain due to lubrication and nutrition to the avascular areas of the disc and condylar cartilage. Botulinum toxin (BTX) has been used for years in the medical and cosmetic field, but its use in TMJD refers to injections specifically within masseter muscle, with the objective to reduce the muscular tension TMJ overload, therefore, pain decreases, and movement increases. Over the years these less invasive methods have been increasing in the medical area due to the great pain management in the neuro-muscular and articular complex.

IntroductionFull-thickness rotator cuff tear is present in almost 50% of patients over age 65 years, and its degree is known to be a good predictor of the severity of muscle-wasting (MW) sarcopaenia, also known as fatty degeneration (FD). A FD CT grade > 2° is recognized as a borderline of its reversibility. A disuse model of supraspinatus FD (grade 2) in rabbits provides clinically relevant data. Therefore, the present study evaluates the correlation between eccentric mechanotransduction, neuromuscular transmission (NT), and reversibility of muscle fatty infiltration (MFI) in rabbit supraspinatus FD > 2°.Material and methodsThe supraspinatus tendon was detached from the greater tubercle, infraspinatus, and subscapularis in 16 rabbits. The tendon was reinserted after 12 weeks, and the animals were euthanized 24 weeks after reconstruction. MFI was measured in the middle part of the supraspinatus. Single-fibre EMG (SFEMG) examination of the supraspinatus NT was performed on 4 animals.ResultsThe power of analysis was 99%. Significant differences in MFI volume were found between the operated (4.6 ±1.1%) and the opposite control sides (2.91 ±0.61%) (p < 0.001). SFEMG revealed no significant differences between the disuse and the control supraspinatus muscles (p > 0.05); however, 6.5% of the examined muscle fibres exhibited NT disorders combined with blockade of conduction in 2.5% of muscle fibres.ConclusionsCritical MFI in a disuse model of rabbit supraspinatus FD, CT grade > 2°, is substantially reversible by eccentric training despite subclinical impairment of neuromuscular transmission. In addition, 0.63% reversal of MFI is correlated with 1% hypertrophy of type I and II muscle fibre diameter.

The purpose of this study is to clarify the reactions of the neuro-muscular junction and nerve cell body to gradual nerve elongation. The sciatic nerves of Japanese white rabbits were lengthened by 30 mm in increments of 0.8 mm/day, 2.0 mm/day and 4.0 mm/day. A scanning electron microscopic examination showed no degenerative change at the neuro-muscular junction, even eight weeks after elongation in the 4-mm group. Hence, neuro-muscular junction is not critical for predicting damage from gradual nerve elongation. There were no axon reaction cells in the 0.8-mm group, a small amount in the 2-mm group, and a large amount in the 4-mm group. The rate of growth associated protein-43 positive nerve cells was significant in the 4-mm group. Hence, the safe speed for nerve cells appeared to be 0.8-mm/day, critical speed to be 2.0-mm/day, and dangerous speed to be 4.0-mm/day in this elongation model.

Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset >50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer’s disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.

Neuro-muscular disorders and diseases such as cerebral palsy and Duchenne Muscular Dystrophy can severely limit a person’s ability to perform activities of daily living (ADL). Exoskeletons can provide an active or passive support solution to assist these groups of people to perform ADL. This study presents an artificial neural network-trained adaptive controller mechanism that uses surface electromyography (sEMG) signals from the human forearm to detect hand gestures and navigate an in-house-built wheelchair-mounted upper limb robotic exoskeleton based on the user’s intent while ensuring safety. To achieve the desired position of the exoskeleton based on human intent, 10 hand gestures were recorded from 8 participants without upper limb movement disabilities. Participants were tasked to perform water bottle pick and place activities while using the exoskeleton, and sEMG signals were collected from the forearm and processed through root mean square, median filter, and mean feature extractors prior to training a scaled conjugate gradient backpropagation artificial neural network. The trained network achieved an average of more than 93% accuracy, while all 8 participants who did not have any prior experience of using an exoskeleton were successfully able to perform the task in less than 20 s using the proposed artificial neural network-trained adaptive controller mechanism. These results are significant and promising thus could be tested on people with muscular dystrophy and neuro-degenerative diseases.

Aim. To assess the application of intraoperative neurophysiological monitoring (IONM) for spinal surgeries in accordance with the Federal Center of Traumatology, Orthopedics and Endoprosthesis (Cheboksary, Russian Federation)Material and methods. A total of 366 spinal surgeries, Federal Center of Traumatology, Orthopedics and Endoprosthesis from 2009 to 2015. From 2009 to 2013, the wake-up test was used as a control method in 116 (65.9%) cases.Results. Application of IONM revealed time-dependent risks and facilitated a reduction in the incidence of postoperative neurologic complications by 3-fold (from 2.6% to 0.8%). In the second half of 2013, IONM was introduced for use in clinical practice. Since then, 250 surgeries were performed with IONM. Of these, the wake-up test was required in 9 (3.6%) patients. Clinical implementation of IONM extended the benefits of surgery to patients with severe pathologies. The number of surgeries for congenital pathologies increased by 10-fold (from 1% to 10%) and by 2.6-fold for degenerative diseases. IONM possibility allows control of intraoperative neurologic complications among patients with spinal injuries (5%) and neuro and muscular scoliosis.Conclusions. The application of IONM minimized the need for the wake-up test and significantly decreased the incidence of neurological complications caused by injury to the spinal cord and spinal roots during execution of spinal manipulations.

A esclerose lateral amiotrófica (ELA) pode ser definida como uma doença neurológica progressiva, degenerativa e inexorável, cuja gênese ainda é de difícil entendimento. Fatores vários contribuem na desprogramação e morte celular precoces. A busca por uma melhor inter-relação, em novos marcadores e associações com tipos celulares e\ou moleculares distintos parece o grande desafio. O delineamento de pesquisas clinicas em (ELA), com informações a respeito de tipo, ação e dose de medicamentos emergem à medida que novas teorias são apresentadas e somadas ao modelo atual [1,2].Definitivamente a ELA é uma doença multifatorial. O estresse oxidativo, excitotoxicidade mediada pelo glutamato, efeitos causados pela mutação do superóxido dismutase, agregação anormal proteíco-especifica, desestruturação de neuro-filamentos intermediários, alteração do transporte axonal anterógrado e retrógrado, ativação microglial, inflamação e transtornos nos fatores de crescimento, têm sido considerados como potenciais agressores aos neurônios motores. Fatores genéticos, influxo excessivo de cálcio intracelular e apoptose também fazem parte desse compreensível mas ainda indecifrável modelo teórico [3].Baseado no exposto sobre a fisiopatologia da ELA, bem como sobre as manifestações clínicas dessa doença, torna-se evidente a necessidade de atuação multidisciplinar, em especial do fisioterapeuta desde o momento do diagnóstico clínico, e que será o responsável pela prescrição dos exercícios terapêuticos.Mas o que esperamos da relação anabolismo vs. catabolismo, uma vez que desde a fase inicial da ELA preconiza-se a realização de exercício terapêuticos das mais diversas naturezas (aeróbicos, resistido, respiratórios etc), porém a cadeia de eventos devastadores inerentes à fisiopatologia da ELA já estão em franca evolução? Respeitando tanto os objetivos terapêuticos como as fases da ELA, a prescrição do fortalecimento muscular e o recondicionamento físico tornam-se componentes do programa de tratamento estabelecido pela da fisioterapia, e diversos estudos são encontrados na literatura, e que sustentam sua prática, porém com resultados controversos [4-6]. Podemos dividir o gasto energético diário em três componentes: taxa metabólica basal, efeito térmico do alimento e gasto energético associado com a atividade física. A realização de um exercício físico promove aumento do gasto energético total, tanto aguda, quanto cronicamente. No que tange o efeito agudo, encontra-se bem estabelecido que após o término da atividade, o consumo de oxigênio (VO2) não retorna aos valores de repouso, imediatamente. Essa demanda energética durante o período de recuperação após o exercício, que é necessária para “quitar a divida metabólica assumida durante a realização da atividade” é definida como excess post-erxercise oxygen consumption ou consumo excessivo de oxigênio após o exercício (EPOC) [7,8]. Em virtude do grande desajuste metabólico que envolve a ELA, e do franco estado catabólico, o questionamento que deve ser feito é, se a intensidade do exercício prescrito não irá gerar um efeito EPOC, que pode vir a ser prejudicial a esse grupo de pacientes? Seria então essa “dívida metabólica” mais um trabalho a ser executado por um organismo deveras debilitado e em franco catabolismo? Existem novas possibilidades terapêuticas num arcabouço fisiopatológico ainda em construção, uma delas é a proposta do protocolo Deanna [9] que sugere a suplementação de arginina-alfa-cetoglurarato, complexo B, dentre outras poderiam atenuar a disfunção mitocondrial, excitotoxicidade do glutamato e estresse oxidativo. É fundamental que a prescrição do exercício seja em intensidade submáxima (40 -60% VO2pico, ou 60 – 85% FCmáx ou 10-13 na escala de Borg) tanto pelo aspecto que envolve o efeito EPOC, assim como pelos efeitos diretamente relacionados ao metaborreflexo da musculatura periférica e respiratória. Pautados nesses conceitos não contra indicamos a prescrição do fortalecimento muscular e o recondicionamento físico e portadores de ELA, porém sugerimos que todos esses aspectos sejam contemplados na prescrição.

Parkinson’s disease (PD) is the most common neurodegenerative disorder after Alzheimer’s disease with approximately 7 million patients worldwide which are predicted to get doubled by 2030. The most common form of PD is the sporadic form with no known cause. Amongst many factors responsible for the pathogenesis of sporadic PD, Cell cycle reentry (CCE) with subsequent DNA synthesis in at-risk dopaminergic neurons has been recently identified as the cause of neuronal cell death. Neurons are post-mitotic cells which never divide, but in lieu of their physiological demands certain cell cycle proteins are utilized. However, under the influence of various stressors cell cycle is re-activated in a full blown manner and owing to mitotic incompetence of neurons, drive them to death. Mounting evidence has outlined the causal role of CCE in the pathogenesis of PD and other neurodegenerative disorders. Moreover, certain protective proteins such as ubiquitin E3 ligases and heat shock proteins play crucial role in maintaining protein homeostasis and in alleviating toxic protein burden in various neurodegenerative disorders thereby, promoting neuronal cell survival. The present work aims to study the involvement of cell cycle proteins in neuronal apoptosis and to underline the role of protective proteins especially HSP70 in neuronal cell viability. The study uses widely known toxin rotenone to mimic PD in SH-SY5Y neuroblastoma cell lines. The results show upregulation of cyclin E with subsequent attenuation of ubiquitin E3 ligase parkin and HSP70 in response to rotenone administration. Further, screening of HSP70 inducing biomolecules have clearly outlined their neuroprotective potential in attenuating CCE led neuronal death and in modifying and reversing rotenone induced toxicity. Thus, the present work opens up a new avenue of using HSP70 inducing compounds to target CCE mediated neuronal death in PD which can be extended to other neurodegenerative disorders

People with (neuro-)muscular diseases have problems lifting their arms against gravity because of degeneration of their muscles. Many of them are in need of a device that supports the weight of their arms, so as to regain some independence. Existing solutions do not meet all of the requirements. This paper presents the design of a new type of spring-compensation mechanism which is adjustable to varying load. The most important part of this design is a wrapping cam with variable transmission to compensate for errors, which rolls on a support plane to minimize friction.