Antioxidant effects of LEDT in dystrophic muscle cells: involvement of PGC-1α and UCP-3 pathways.

PURPOSE: Reactive oxygen species and mitochondrial dysfunction play a crucial role in the pathophysiology of Duchenne muscular dystrophy (DMD). The light-emitting diode therapy (LEDT) showed beneficial effects on the dystrophic muscles. However, the mechanisms of this therapy influence the molecular pathways in the dystrophic muscles, particularly related to antioxidant effects, which still needs to be elucidated. The current study provides muscle cell-specific insights into the effect of LEDT, 48 h post-irradiation, on oxidative stress and mitochondrial parameters in the dystrophic primary muscle cells in culture. METHODS: Dystrophic primary muscle cells were submitted to LEDT, at multiple wavelengths (420 nm, 470 nm, 660 nm and 850 nm), 0.5 J dose, and evaluated after 48 h based on oxidative stress markers, antioxidant enzymatic system and biogenesis, and functional mitochondrial parameters. RESULTS: The mdx muscle cells treated with LEDT showed a significant reduction of H2O2 production and 4-HNE, catalase, SOD-2, and GR levels. Upregulation of UCP3 was observed with all wavelengths while upregulation of PGC-1α and a slight upregulation of electron transport chain complexes III and V was only observed following 850 nm LEDT. In addition, the mitochondrial membrane potential and mitochondrial mass mostly tended to be increased following LEDT, while parameters like O2·- production tended to be decreased. CONCLUSION: The data shown here highlight the potential of LEDT as a therapeutic agent for DMD through its antioxidant action by modulating PGC-1α and UCP3 levels.

Photobiomodulation Therapy on the Treatment of Insulin Resistance: A Narrative Review.

Background: Insulin resistance (IR) is the main risk factor for the development of type 2 diabetes mellitus (DM2). Noninvasive and nonpharmacological therapies, such as exercise and diet are effective in treating IR and DM2; however, adherence to them generally is low and diminishes positive effects in the long term. Photobiomodulation therapy (PBMT) is another noninvasive and nonpharmacological therapy, which produces positive effects on mitochondrial metabolism, oxidative stress, and inflammation generally linked to IR and DM2 and may improve or attenuate the severity of these diseases. Objective: In this narrative review, we focus on the available literature related to the effects of PBMT on IR. Results: In fact, recent in vitro and in vivo studies have demonstrated improvements in IR in skeletal muscle, adipose tissue, and hepatic cells mediated by PBMT. Further, there is evidence that PBMT can potentiate exercise-induced improvement in IR through ameliorating mitochondrial dysfunction, reducing inflammation, and modulating oxidative stress. Moreover, reduced adiposity and altered gut microbiota also appear to mediate PBMT effects on IR. Conclusions: Although these results are exciting, randomized clinical trials are urgently needed to confirm the clinical relevance of PBMT in the treatment of IR. Investigation about the effects of PBMT combined with different volumes of physical exercises may also contribute significantly for those patients having difficulty to adhere to the recommended minimal exercise volume. Finally, studies on PBMT parameters (e.g., dosimetry, wavelengths, single-point vs. full-body irradiation) are also necessary for the appropriate prescription of PBMT for the treatment of IR.

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.

Exploring the ability of low-level laser irradiation to reduce myonecrosis and increase Myogenin transcription after Bothrops jararacussu envenomation.

Envenoming caused by snakebites is a very important neglected tropical disease worldwide. The myotoxic phospholipases present in the bothropic venom disrupt the sarcolemma and compromise the mechanisms of energy production, leading to myonecrosis. Photobiomodulation therapy (PBMT) has been used as an effective tool to treat diverse cases of injuries, such as snake venom-induced myonecrosis. Based on that, the aim of this study was to analyze the effects of PBMT through low-level laser irradiation (904 nm) on the muscle regeneration after the myonecrosis induced by Bothrops jararacussu snake venom (Bjssu) injection, focusing on myogenic regulatory factors expression, such as Pax7, MyoD, and Myogenin (MyoG). Male Swiss mice (Mus musculus), 6-8-week-old, weighing 22 ± 3 g were used. Single sub-lethal Bjssu dose or saline was injected into the right mice gastrocnemius muscle. At 3, 24, 48, and 72 h after injections, mice were submitted to PBMT treatment. When finished the periods of 48 and 72 h, mice were euthanized and the right gastrocnemius were collected for analyses. We observed extensive inflammatory infiltrate in all the groups submitted to Bjssu injections. PBMT was able to reduce the myonecrotic area at 48 and 72 h after envenomation. There was a significant increase of MyoG mRNA expression at 72 h after venom injection. The data suggest that beyond the protective effect promoted by PBMT against Bjssu-induced myonecrosis, the low-level laser irradiation was able to stimulate the satellite cells, thus enhancing the muscle repair by improving myogenic differentiation.

Specific modulation of corticomuscular coherence during submaximal voluntary isometric, shortening and lengthening contractions.

During voluntary contractions, corticomuscular coherence (CMC) is thought to reflect a mutual interaction between cortical and muscle oscillatory activities, respectively measured by electroencephalography (EEG) and electromyography (EMG). However, it remains unclear whether CMC modulation would depend on the contribution of neural mechanisms acting at the spinal level. To this purpose, modulations of CMC were compared during submaximal isometric, shortening and lengthening contractions of the soleus (SOL) and the medial gastrocnemius (MG) with a concurrent analysis of changes in spinal excitability that may be reduced during lengthening contractions. Submaximal contractions intensity was set at 50% of the maximal SOL EMG activity. CMC was computed in the time-frequency domain between the Cz EEG electrode signal and the unrectified SOL or MG EMG signal. Spinal excitability was quantified through normalized Hoffmann (H) reflex amplitude. The results indicate that beta-band CMC and normalized H-reflex were significantly lower in SOL during lengthening compared with isometric contractions, but were similar in MG for all three muscle contraction types. Collectively, these results highlight an effect of contraction type on beta-band CMC, although it may differ between agonist synergist muscles. These novel findings also provide new evidence that beta-band CMC modulation may involve spinal regulatory mechanisms.

Modulation of torque evoked by wide-pulse, high-frequency neuromuscular electrical stimulation and the potential implications for rehabilitation and training.

The effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: - 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.

Effects of Photobiomodulation Therapy (LED 630 nm) on Muscle and Nerve Histomorphometry after Axonotmesis.

Peripheral injuries constitute a substantial clinical problem with unsatisfactory treatment. The study's objective was to analyze the effects of photobiomodulation therapy (PBMT) on median nerve regeneration and muscle recovery after axonotmesis. Twenty-four rats were randomized into three groups: control (CG), injury (IG), and LED therapy (LEDG). A 630 ± 20 nm (300-mW) LED was placed in contact with the skin. One point over the injury site was irradiated for 30 s, delivering 9 J (9 J cm-2 ). PBMT irradiation was performed once daily for 5 days followed by two-day interval and then more five consecutive days of treatment. Proximal and distal segments of the nerve and flexors muscles were removed for histomorphometric analysis using H&E staining for muscles and osmium tetroxide for nerves. The myelinated fiber and axon diameter and the myelin sheath thickness were greater in the proximal and distal nerve segments in the LEDG compared to the IG (P ≤ 0.05). The number of myelinated fibers was greater in the distal segment of the LEDG (P ≤ 0.05). The area, circumference, and diameter of the muscle fibers were larger in the LEDG than in the IG (P ≤ 0.05). The PBMT protocol used favored axonal regeneration and muscle recovery.

The Prognostic Relevance of Computed Tomography-assessed Skeletal Muscle Index and Skeletal Muscle Radiation Attenuation in Patients With Gynecological Cancer.

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer.

Effect of Long-Term Light Deprivation on α-Tocopherol Content in Rats during Ontogeny.

We studied the effect of long-term light deprivation which began at different stages of ontogeny on the content of α-tocopherol in rats during the first 3 months of postnatal development. In the offspring postnatally exposed to constant darkness, the level of α-tocopherol in the liver, kidneys, heart, skeletal muscles, and lungs was significantly decreased at the early stages of postnatal ontogeny (2 weeks and 1 month). In rats kept under constant darkness after birth, the content of α-tocopherol in the lungs was also reduced at the age of 1 month. The modulating effect of light deprivation on the level of α-tocopherol can be associated both with the impact of disturbed circadian rhythms and with increased content of melatonin in the body.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Photobiomodulation modulates the expression of inflammatory cytokines during the compensatory hypertrophy process in skeletal muscle.

Compensatory hypertrophy (CH) occurs due to excessive mechanical load on a muscle, promoting an increase in the size of muscle fibers. In clinical practice, situations such as partial nerve injuries, denervation, and muscle imbalance caused by trauma to muscles and nerves or diseases that promote the loss of nerve conduction can induce CH in muscle fibers. Photobiomodulation (PBM) has demonstrated beneficial effects on muscle tissue during CH. The aim of the present study was to evaluate the effect of PBM on the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) as well as type 2 metalloproteinases (MMP-2) during the process of CH due to excessive load on the plantaris muscle in rats. Forty-five Wistar rats weighing 250 g were divided into three groups: control group (n = 10), hypertrophy (H) group (n = 40), and H + PBM group (n = 40). CH was induced through the ablation of synergist muscles of the plantaris muscle. The tendons of the gastrocnemius and soleus muscles were isolated and sectioned to enable the partial removal of each of muscle. The preserved plantaris muscle below the removed muscles was submitted to excessive functional load. PBM was performed with low-level laser (AsGaAl, λ = 780 nm; 40 mW; energy density: 10 J/cm2; 10 s on each point, 8 points; 3.2 J). Animals from each group were euthanized after 7 and 14 days. The plantaris muscles were carefully removed and sent for analysis of the gene and protein expression of IL-6 and TNF-α using qPCR and ELISA, respectively. MMP-2 activity was analyzed using zymography. The results were submitted to statistical analysis (ANOVA + Tukey's test, p < 0.05). The protein expression analysis revealed an increase in IL-6 levels in the H + PBM group compared to the H group and a reduction in the H group compared to the control group. A reduction in TNF-α was found in the H and H + PBM groups compared to the control group at 7 days. The gene expression analysis revealed an increase in IL-6 in the H + PBM group compared to the H group at 14 days as well as an increase in TNF-α in the H + PBM group compared to the H group at 7 days. Increases in MMP-2 were found in the H and H + PBM groups compared to the control group at both 7 and 14 days. Based on findings in the present study, it is concluded that PBM was able to modulate pro-inflammatory cytokines that are essential for the compensatory hypertrophy process. However, it has not shown a modulation effect directly in MMP-2 activity during the same period evaluated.

Gamma-ray buildup factor and radiation absorbed dose enhancement at tissue-bone interfaces.

During superficial radiotherapy, and for cases where bony structures lie relatively close to the surface behind the tissue region being treated, perturbations to delivered dose are expected due to the change in tissue scattering conditions and the value of buildup factor near the tissue/bone interface. The absorbed dose distribution within bone, muscle, and muscle-bone-muscle interfaces was estimated for photons within the energy range 0.05 to 1.333 MeV. The energy absorption buildup factor is computed using the (GP) fitting method for a geometry of adjacent layers within a multilayer tissue matrix where a thick slab of solid bone is located in-between slabs of muscles of the same thickness. It was observed that dose enhancement was limited only to a few millimeters close to the interface. Also, variations in dose at the interface were found significant only for low photon energies and relatively insignificant at photon energies higher than 0.06 MeV.

Characterization of macrophages, giant cells and granulomas during muscle regeneration after irradiation.

Macrophages play a fundamental role in the different stages of muscle regeneration although the precise mechanisms involved are not entirely understood. Here we investigated the types of macrophages and cytokines that appeared in muscles after local gamma irradiation of mini-pigs that underwent no subsequent treatment or received three successive adipose tissue-derived stem cell (ASC) injections. Although some variability was observed among the three animals included in each study group, a general picture emerged. No macrophages appeared in control muscles from regions that had not been irradiated nor in muscles from irradiated regions derived from two animals. A third irradiated, but untreated animal, with characteristic muscle fibrosis and necrosis due to irradiation, showed invasion of M2 macrophages within small muscle lesions. In contrast, among the three ASC-treated and irradiated animals, one of them had completely recovered normal muscle architecture at the time of sampling with no invading macrophages, muscle from a second one contained mostly M1 macrophages and some M2-like macrophages whereas muscle from a third one displayed granulomas and giant cells. ASC treatment was associated with the presence of similar levels of pro-inflammatory cytokines within the two animals in the process of muscle regeneration whereas the levels of IL-4 and IL-10 expression were distinct from one animal to another. Microspectrofluorimetry and in situ hybridization revealed strong expression of TGF-ß1 and TNFα in regenerating muscle. Overall, the data confirm the critical role of macrophages in muscle regeneration and suggest the involvement of a complex network of cytokine expression for successful recovery.

Irradiated Skeletal Muscle Cells Mimicking Those of Atypical Fibroxanthoma on Mohs Frozen Sections.

ABSTRACT: Radiation can induce changes to skeletal muscle cells that may mimic and thus be confused with cells of atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma, spindle cell squamous cell carcinoma, and other spindle soft-tissue tumors. An 80-year-old White man presented for Mohs micrographic surgery of an AFX on the left lateral neck. The medical history was notable for a tongue squamous cell carcinoma 9 years before that had been treated with wide local excision, left neck dissection, and radiation to the oral cavity and left neck. Frozen sections from the first stage of Mohs did not show typical AFX, but did reveal patchy clusters of atypical spindled and epithelioid cells, some with multiple nuclei. Because of the unusual appearance of these cells, Mohs micrographic surgery was halted, and the frozen tissue block was sent for permanent pathology examination. The cells on permanent sections stained positive for desmin, revealing them to be of skeletal muscle origin (in this case damaged platysma muscle because of late postradiation changes). It is thus important for the Mohs surgeon and the consultant dermatopathologist to be aware of the unusual histologic appearance of irradiated skeletal muscle to avoid confusion with other spindle cell tumors.

Scalable Microgravity Simulator Used for Long-Term Musculoskeletal Cells and Tissue Engineering.

We introduce a new benchtop microgravity simulator (MGS) that is scalable and easy to use. Its working principle is similar to that of random positioning machines (RPM), commonly used in research laboratories and regarded as one of the gold standards for simulating microgravity. The improvement of the MGS concerns mainly the algorithms controlling the movements of the samples and the design that, for the first time, guarantees equal treatment of all the culture flasks undergoing simulated microgravity. Qualification and validation tests of the new device were conducted with human bone marrow stem cells (bMSC) and mouse skeletal muscle myoblasts (C2C12). bMSC were cultured for 4 days on the MGS and the RPM in parallel. In the presence of osteogenic medium, an overexpression of osteogenic markers was detected in the samples from both devices. Similarly, C2C12 cells were maintained for 4 days on the MGS and the rotating wall vessel (RWV) device, another widely used microgravity simulator. Significant downregulation of myogenesis markers was observed in gravitationally unloaded cells. Therefore, similar results can be obtained regardless of the used simulated microgravity devices, namely MGS, RPM, or RWV. The newly developed MGS device thus offers easy and reliable long-term cell culture possibilities under simulated microgravity conditions. Currently, upgrades are in progress to allow real-time monitoring of the culture media and liquids exchange while running. This is of particular interest for long-term cultivation, needed for tissue engineering applications. Tissue grown under real or simulated microgravity has specific features, such as growth in three-dimensions (3D). Growth in weightlessness conditions fosters mechanical, structural, and chemical interactions between cells and the extracellular matrix in any direction.

Thermographic response resulting from strength training: A preliminary study

INTRODUCTION: Exercise induces modifications in thermal homeostasis. The type of exercise may have a specific impact on skin temperature (Tsk). OBJECTIVE: To analyze and compare the behavior of Tsk in a resistance training between men and women and monitor the thermal recovery response. MATERIAL AND METHODS: Sixteen male and female adults (24.56±3.22 years old) underwent a resistance circuit training session. They performed 3 sets of 12 repetitions with 70-80% 1 RM for lat pulldown, leg press, and biceps arm curl exercises. Thermograms were taken in anterior and posterior body view at rest, 20min, and 24h after training. Tsk was measured in the body regions of interest corresponding to the brachial biceps, quadriceps, and upper back. ANOVA with Tukey's post hoc test was used to analyze Tsk changes among moments, and independent samples t-test was used to compare Tsk between males and females. RESULTS: At rest, women showed Tsk significantly lower than men. There was no significant Tsk change 20min after exercise. However, Tsk increased 24h after exercise in the upper back for men compared with baseline and in quadriceps for women compared with baseline and 20min after exercise (p < 0.05). CONCLUSION: The Tsk of women at rest is lower than that of men. A resistance circuit training session does not significantly change Tsk 20min after exercise, but it increases Tsk 24h after training in the upper back for men and quadriceps for women

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Bidirectional myofiber transition through altering the photobiomodulation condition.

Despite remarkable advancements in modern medicine, muscular atrophy remains as an unsolved problem. It is well known that pathological characteristics of different atrophy types could vary according to the pathophysiological causes. In fact, the lesion of atrophy is not always homogenously distributed but often predominantly evident in either fast or slow myofibers. As the focalization of the atrophic lesions, the existence and the functional impairment of each fast and slow progenitor/satellite cell (SC) are suspected though there are still controversies about this hypothesis. In this study, we isolated Pax7 positive (Pax7+ve) SCs from the tibia anterior (fast) and soleus (slow) muscles respectively and successfully demonstrated, for the first time, the difference between optimal exposure durations of photobiomodulation (PBM) which was known as low level laser irradiation (LLLI) in promoting proliferation of Pax7+ve SC which were acquired from fast and slow muscles respectively. Moreover, a hypertrophy-accompanied bidirectional change in myofiber composition with neuromuscular junction alteration, either from slow to fast or fast to slow, were achieved by applying different PBM durations. Simultaneously, PBM exhibited a synergistic effect with muscle exercise on the increase in myofiber size. Our data suggested the existence of at least two different populations of Pax7+ve SC which possess distinct sensitivities towards PBM. As our data revealed the capability of PBM in bidirectional changes of skeletal muscle composition and neuromuscular junction constitution thereby strengthen its contractility through altering the irradiation condition, we believe PBM showed the potential to be as a promising clinical treatment for muscular atrophy.

Low-Level Laser Therapy in Different Wavelengths on the Tibialis Anterior Muscle of Wistar Rats After Nerve Compression Injury.

OBJECTIVE: Traumatic injuries are common and may promote disruption of neuromuscular communication, triggering phenomena that lead to nerve degeneration and affect muscle function. A laser accelerates tissue recovery; however, the parameters used are varied, making it difficult to compare studies. The purpose of this study was to evaluate the effect of low-level laser therapy, at 660- and 830-nm wavelengths, on the tibialis anterior muscle of Wistar rats after sciatic nerve compression. METHODS: Twenty animals were separated into 4 groups: control, sciatic nerve injury, lesion + 660-nm laser, and lesion + 830-nm laser. In the lesion groups, the right sciatic nerve was surgically exposed and compressed with hemostatic forceps for 30 seconds. After the third postoperative day, the groups with laser therapy were submitted to treatment for 2 weeks totaling 10 applications, performed directly on the surgical scar of the nerve injury. Grip strength was analyzed before and after the nerve injury and during the treatment period. The tibialis anterior muscle was processed for light microscopy, area measurement, smaller diameter, number of fibers, nuclei, and connective tissue. RESULTS: The animals submitted to the injury experienced muscular atrophy and morphological changes in the number of muscle fibers and nuclei. In the connective tissue morphometry, there was a decrease in the treated groups compared with the untreated groups. CONCLUSION: The laser treatment at different wavelengths showed no improvement in the tibialis anterior muscle of Wistar rats within the morphological and functional aspects evaluated.

Can photobiomodulation therapy be an alternative to pharmacological therapies in decreasing the progression of skeletal muscle impairments of mdx mice?

OBJECTIVE: To compare the effects of photobiomodulation therapy (PBMT) and pharmacological therapy (glucocorticoids and non-steroidal anti-inflammatory drugs) applied alone and in different combinations in mdx mice. METHODS: The animals were randomized and divided into seven experimental groups treated with placebo, PBMT, prednisone, non-steroidal anti-inflammatory drug (NSAIDs), PBMT plus prednisone and PBMT plus NSAID. Wild type animals were used as control. All treatments were performed during 14 consecutive weeks. Muscular morphology, protein expression of dystrophin and functional performance were assessed at the end of the last treatment. RESULTS: Both treatments with prednisone and PBMT applied alone or combined, were effective in preserving muscular morphology. In addition, the treatments with PBMT (p = 0.0005), PBMT plus prednisone (p = 0.0048) and PBMT plus NSAID (p = 0.0021) increased dystrophin gene expression compared to placebo-control group. However, in the functional performance the PBMT presented better results compared to glucocorticoids (p<0.0001). In contrast, the use of NSAIDs did not appear to add benefits to skeletal muscle tissue in mdx mice. CONCLUSION: We believe that the promising and optimistic results about the PBMT in skeletal muscle of mdx mice may in the future contribute to this therapy to be considered a safe alternative for patients with Duchenne Muscular Dystrophy (DMD) in a washout period (between treatment periods with glucocorticoids), allowing them to remain receiving effective and safe treatment in this period, avoiding at this way periods without administration of any treatment.

Irradiation dependent inflammatory response may enhance satellite cell engraftment.

Skeletal muscle stem (satellite) cells transplanted into host mouse muscles contribute to muscle regeneration. Irradiation of host muscle enhances donor stem cell engraftment by promoting the proliferation of transplanted donor cells. We hypothesised that, similar to other systems, cells damaged by radiation might be effecting this donor cell proliferation. But we found no difference in the percentage of dying (TUNEL+) cells in immunodeficient dystrophic mouse muscles at the times after the irradiation dose that enhances donor cell engraftment. Similarly, irradiation did not significantly increase the number of TUNEL+ cells in non-dystrophic immunodeficient mouse muscles and it only slightly enhanced donor satellite cell engraftment in this mouse strain, suggesting either that the effector cells are present in greater numbers within dystrophic muscle, or that an innate immune response is required for effective donor cell engraftment. Donor cell engraftment within non-irradiated dystrophic host mouse muscles was not enhanced if they were transplanted with either satellite cells, or myofibres, derived from irradiated dystrophic mouse muscle. But a mixture of cells from irradiated muscle transplanted with donor satellite cells promoted donor cell engraftment in a few instances, suggesting that a rare, yet to be identified, cell type within irradiated dystrophic muscle enhances the donor stem cell-mediated regeneration. The mechanism by which cells within irradiated host muscle promote donor cell engraftment remains elusive.