Denervation causes muscle atrophy and incapacity in humans. Although electrical stimulation (ES) and stretching (St) are commonly used in rehabilitation, it is still unclear whether they stimulate or impair muscle recovery and reinnervation. The purpose of this study was to evaluate the effects of ES and St, alone and combined (ES + St), on the expression of genes that regulate muscle mass (MyoD, Runx1, atrogin-1, MuRF1 and myostatin), on muscle fibre cross-sectional area and excitability, and on the expression of the neural cell adhesion molecule (N-CAM) in denervated rat muscle. ES, St and ES + St reduced the accumulation of MyoD, atrogin-1 and MuRF1 and maintained Runx1 and myostatin expressions at normal levels in denervated muscles. None of the physical interventions prevented muscle fibre atrophy or N-CAM expression in denervated muscles. In conclusion, although ES, St and ES + St changed gene expression, they were insufficient to avoid muscle fibre atrophy due to denervation.
Denervation induces muscle fiber atrophy and changes in the gene expression rates of skeletal muscle. Electrical stimulation (ES) is a procedure generally used to treat denervated muscles in humans. This study evaluated the effect of ES based on chronaxie and rheobase on the expression of the myoD and atrogin-1 genes in denervated tibialis anterior (TA) muscle of Wistar rats. Five groups were examined: (1) denervated (D); (2) DϩES; (3) sham denervation; (4) normal (N); and (5) NϩES. Twenty muscle contractions were stimulated every 48 h using surface electrodes. After 28 days, ES significantly decreased the expression of myoD and atrogin-1 in DϩES compared to the D group. However, ES did not prevent muscle-fiber atrophy after denervation. Thus, ES based on chronaxie values and applied to denervated muscles using surface electrodes, as normally used in human rehabilitation, was able to reduce the myoD and atrogin-1 gene expressions, which are related to muscular growth and atrophy, respectively. The results of this study provide new information for the treatment of denervated skeletal muscle using surface ES.
Stretching is widely used in rehabilitation and sports activities to improve joint range-of-motion and flexibility in humans, but the effect of stretching on the gene expression of skeletal muscle is poorly understood. We evaluated the effect of short bouts of passive stretching of rat soleus muscle on myo-D, myostatin, and atrogin-1 gene expressions. Six groups of animals were submitted to a single session of stretching (10 stretches of 1 minute with 30 seconds of rest between them, performed manually) and were evaluated immediately (I), and 8, 24, 48, 72, and 168 hours after the session. To evaluate the effect of repetitive sessions of stretching on the soleus muscle over 1 week, three groups of animals received a single session per day of stretching and the muscle was evaluated immediately after 2, 3, and 7 sessions. The mRNA levels of myo-D, myostatin, and atrogin-1 were determined by real-time polymerase chain reaction. A single session of stretching increased the mRNA levels of myo-D (after 24 h), myostatin (I, and 168 h later), and atrogin-1 (after 48 h). Repeated daily session of stretching over 1 week increased myostatin (after 7 sessions) and atrogin-1 expression (after 2, 3, and 7 sessions). Thus, short bouts of passive stretching are able to increase the gene expression of factors associated with muscle growth (myo-D), negative regulation of muscle mass (myostatin), and atrophy (atrogin-1), indicating muscle remodeling through different pathways.
Muscle-fiber atrophy occurs concomitantly with intramuscular connective tissue proliferation following denervation. These events contribute to the impairment of mechanical and functional properties of denervated muscles and compromise their recovery. Electrical stimulation (ES) is used in human rehabilitation to treat denervated muscles. However, the effects of this therapy on the intramuscular extracellular matrix (ECM) remain uncertain. Metalloproteinases (MMPs) are responsible by remodeling ECM in many neuromuscular disorders. This study evaluates the effect of ES on the activity of two important MMPs, MMP-2 and MMP-9, both involved in ECM remodeling of rat denervated muscles. Thirty-four Wistar rats (3 months old, 356 +/- 38.7 g) were divided into five groups: denervated (D); D+ES; sham denervation; normal (N); and N+ES. Twenty maximal muscle contractions were stimulated every 48 h using surface electrodes, as generally used in the rehabilitation of human denervated muscle. Both zymographic analysis and real-time polymerase chain reaction (PCR) of MMPs were used to evaluate muscle after denervation for 28 days. Both the D and D+ES groups showed increased MMP-2 activity compared with the N group (P < 0.05). Furthermore, only the D+ES had increased MMP-2 gene expression compared with the N group (P < 0.05). MMP-9 activity was not detected in any of the groups. The results of this study indicate that denervation increases MMP-2 activity, and ES regulates MMP-2 gene expression in rat denervated skeletal muscle. These findings clarify the effects of ES on the ECM of denervated muscle and may be helpful in designing new therapeutic strategies for rehabilitation in patients with denervation of muscle.
Quadriceps atrophy after ACL transection involves increased levels of myostatin, atrogin-1, and muscle ring finger 1 mRNA and the accumulation of ubiquitinated protein.
O objetivo foi verificar o efeito de um programa de fisioterapia funcional para crianças com paralisia cerebral, associado a orientações aos pais e/ou cuidadores; e verificar a correlação entre as habilidades funcionais e a assistência do cuidador, utilizando o Inventário de Avaliação Pediátrica de Incapacidade (PEDI). Participaram quatro crianças entre 24 e 43 meses de idade, hemiplégicas, espásticas e nível I no sistema de classificação da função motora ampla (GMFCS). Foram realizadas quatro avaliações - uma antes do início do programa, as demais aos 30, 60 e 90 dias após a primeira -, empregando-se as partes I (Habilidades funcionais) e II (Assistência do cuidador) do PEDI. As crianças foram submetidas a sessões de uma hora de fisioterapia funcional três vezes por semana, durante três meses: duas vezes a sessão era de fisioterapia com base no conceito neuroevolutivo Bobath e uma vez, treino de atividades da vida diária. Também foram dadas orientações por escrito aos pais e/ou cuidadores quanto à assistência à criança, incentivando-os a praticá-la em casa. A análise dos resultados mostrou que, na última avaliação, as crianças obtiveram escores significativamente maiores que na primeira. Foi verificada correlação altamente significativa (r=1,0; p=0,083) entre as partes I e II. O programa de fisioterapia funcional associado às orientações aos pais e/ou cuidadores foi efetivo em melhorar o desempenho funcional de crianças nível I com hemiplegia espástica.
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