[Show abstract][Hide abstract] ABSTRACT: This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.
[Show abstract][Hide abstract] ABSTRACT: β2-adrenergic stimulation causes beneficial effects on structure and function of regenerating muscles; thus the β2-adrenoceptor may play an important role in the muscle regenerative process. Here we investigated the role of the β2 -adrenoceptor in skeletal muscle regeneration. Methods Tibialis anterior muscles from β2-adrenoceptor knockout (β2 KO) mice were cryolesioned and analysed after 1, 3, 10, and 21 days. The role of β2-adrenoceptor on regenerating muscles was assessed through the analysis of morphological and contractile aspects, M1 and M2 macrophage profile, cAMP content, and activation of TGF-β signalling elements.
[Show abstract][Hide abstract] ABSTRACT: This work investigated the effect of gallium arsenide (GaAs) irradiation (power: 5 mW; intensity: 77.14 mW/cm(2), spot: 0.07 cm(2)) on regenerating skeletal muscles damaged by crotoxin (CTX). Male C57Bl6 mice were divided into six groups (n = 5 each): control, treated only with laser at doses of 1.5 J or 3 J, CTX-injured and, CTX-injured and treated with laser at doses of 1.5 J or 3 J. The injured groups received a CTX injection into the tibialis anterior (TA) muscle. After 3 days, TA muscles were submitted to GaAs irradiation at doses of 1.5 or 3 J (once a day, during 5 days) and were killed on the eighth day. Muscle histological sections were stained with hematoxylin and eosin (H&E) in order to determine the myofiber cross-sectional area (CSA), the previously injured muscle area (PIMA) and the area density of connective tissue. The gene expression of MyoD and myogenin was detected by real-time PCR. GaAs laser at a dose of 3 J, but not 1.5 J, significantly increased the CSA of regenerating myofibers and reduced the PIMA and the area density of intramuscular connective tissue of CTX-injured muscles. MyoD gene expression increased in the injured group treated with GaAs laser at a dose of 1.5 J. The CTX-injured, 3-J GaAs laser-treated, and the CTX-injured and treated with 3-J laser groups showed an increase in myogenin gene expression when compared to the control group. Our results suggest that GaAs laser treatment at a dose of 3 J improves skeletal muscle regeneration by accelerating the recovery of myofiber mass.
Lasers in Medical Science 12/2011; 27(5):993-1000. DOI:10.1007/s10103-011-1031-x · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Skeletal muscles from old rats fail to completely regenerate following injury. This study investigated whether pharmacological stimulation of β2-adrenoceptors in aged muscles following injury could improve their regenerative capacity, focusing on myofiber size recovery. Young and aged rats were treated with a subcutaneous injection of β2-adrenergic agonist formoterol (2 μg/kg/d) up to 10 and 21 days after soleus muscle injury. Formoterol-treated muscles from old rats evaluated at 10 and 21 days postinjury showed reduced inflammation and connective tissue but a similar number of regenerating myofibers of greater caliber when compared with their injured controls. Formoterol minimized the decrease in tetanic force and increased protein synthesis and mammalian target of rapamycin phosphorylation in old muscles at 10 days postinjury. Our results suggest that formoterol improves structural and functional regenerative capacity of regenerating skeletal muscles from aged rats by increasing protein synthesis via mammalian target of rapamycin activation. Furthermore, formoterol may have therapeutic benefits in recovery following muscle damage in senescent individuals.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 11/2011; 67(5):443-55. DOI:10.1093/gerona/glr195 · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peripheral nerve injury causes prolonged functional limitation being a clinical challenge to identify resources that accelerates its recovery.
To investigate the effect of high-voltage electrical stimulation (HVES) on the morphometric and functional characteristics of the regenerated nerve after crush injury in rats.
Twenty Wistar rats were randomly allocated into 4 groups: Control (CON) - without injury and without HVES; Denervated (D) - sciatic nerve crush only; Denervated + HVES - sciatic nerve crush and HVES; SHAM - without injury but HVES. The HVES and SHAM groups were stimulated (100 Hz; minimum voltage of 100 V, 20 μs, 100 μs interpulse interval) for 30 min/day, 5 days/week. The sciatic functional index (SFI) was evaluated before the injury and at the 7th, 14th and 21st postoperatory (PO) days. Neural components and the area density of connective tissue, blood vessels and macrophages were analyzed.
Axonal diameter was higher on the HVES than on D group, reaching almost 80% above the control values after 21 days (p<0.05). Fiber diameter and myelin sheath thickness were higher on the HVES than on D group (p<0.05) reaching 96.5% and 100% of the control values, respectively. Functional recovery at the 14th PO day was better on group HVES. The macrophages and connective tissue area density was lower on the HVES group, while blood vessels number did not differ among groups.
The HVES accelerated the functional recovery, potentiated the nerve fibers maturation and decreased macrophages and connective tissue area density, suggesting acceleration of neural repair.
Revista Brasileira de Fisioterapia 01/2011; 15(4):325-31. DOI:10.1590/S1413-35552011005000008 · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This work was undertaken to provide further insight into the role of mammalian target of rapamycin complex 1 (mTORC1) in skeletal muscle regeneration, focusing on myofiber size recovery. Rats were treated or not with rapamycin, an mTORC1 inhibitor. Soleus muscles were then subjected to cryolesion and analyzed 1, 10, and 21 days later. A decrease in soleus myofiber cross-section area on post-cryolesion days 10 and 21 was accentuated by rapamycin, which was also effective in reducing protein synthesis in these freeze-injured muscles. The incidence of proliferating satellite cells during regeneration was unaltered by rapamycin, although immunolabeling for neonatal myosin heavy chain (MHC) was weaker in cryolesion+rapamycin muscles than in cryolesion-only muscles. In addition, the decline in tetanic contraction of freeze-injured muscles was accentuated by rapamycin. This study indicates that mTORC1 plays a key role in the recovery of muscle mass and the differentiation of regenerating myofibers, independently of necrosis and satellite cell proliferation mechanisms.