5 research outputs found
Intraneural application of botulinum neurotoxin a improves motoneuron innervation and functional recovery after femoral nerve reconstruction in rats
No full textAxonal injuries to motoneurons of adult mammals cause, among other responses, loss of synaptic terminals from their cell bodies and dendrites. This “synaptic stripping” is largely, but not always completely reversed after successful axonal regeneration and muscle reinnervation. Long-lasting deficits in, e.g., cholinergic and glutamatergic afferent terminals, correlate negatively with degree of functional recovery in rats suggesting that persistent partial deafferentation of motoneurons may be a factor limiting functional recovery after peripheral nerve injury. AimsTo further explore the idea that functional recovery is partially linked to restoration of synaptic inputs to regenerated motoneurons, we pursued to modulate the deafferentation of motoneurons following nerve section/suture and monitor the effects of this manipulation on the outcome of peripheral nerve regeneration. Two neuroactive molecules, botulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF), known for their ability to influence synaptic inputs to neurons, were selected as manipulation tools. Drug solutions were applied to the proximal stump of the freshly cut femoral nerve of rats to achieve drug uptake and transport to the neuronal perikarya and possibly transcytosis to afferent synapses. The experiments were performed in adult (10-week-old) female Wistar rats which received either BoNT (N = 17), BDNF (N = 15) or bovine serum albumin treatment (BSA, control, N = 13). After drug application, the femoral nerve was surgically reconstructed and functional recovery was monitored over a 5-month period using an established gait analysis protocol. Other outcome measures were quality of endplate reinnervation (occurrence of abnormal polyinnervation assessed morphologically) and numbers of cholinergic, GABA/glycinergic and glutamatergic synaptic terminals in the femoral motor nucleus in the spinal cord (assessed using stereological approaches). Application of BoNT, but not BDNF, resulted in a marked, as compared with BSA, improvement of motor recovery at 2 to 20 weeks after injury. At two months, BoNT-treated rats had an attenuated loss of perisomatic cholinergic terminals compared with the other two treatments. Analysis of individual animal data revealed significant linear correlations between functional parameters and numbers of cholinergic terminals. Quality of endplate reinnervation was not affected by treatment with BoNT or BDNF. The effect of BoNT on synaptic terminals is possibly related to transcytosis of BoNT into perisomatic nerve terminals as suggested by immunohistochemical analysis of cleaved SNAP-25. In turn, better preservation of modulatory cholinergic terminals, which are crucial for normal motoneuron excitability, might underlie enhanced recovery of function in BoNT-treated rats. The findings support the idea that persistent partial deafferentation of axotomized motoneurons is a factor contributing to deficient functional recovery after nerve injury. Intraneural application of drugs appears to be a promising way to analyze causal relationships between synaptic plasticity and restoration of function. In addition, it is thinkable that the described drug application approach may evolve into a clinically feasible therapy if further controlled animal experiments provide convincing evidence for its safety and efficacy.Läsionen peripherer Nerven von erwachsenen Säugetieren verursachen Verlust von Synapsen an Zellkörpern und Dendriten von Motoneuronen. Diese Deafferenzierung (“synaptic stripping“) ist, selbst nach erfolgreicher Nervenregeneration und Reinnervation der Muskulatur, nicht immer vollkommen reversibel. Langfristige Defizite sind für cholinerge und glutamaterge Afferenzen nachgewiesen und diese korrelieren negativ mit dem Grad der funktionellen Erholung bei Ratten. Es kann angenommen werden, dass eine persistierende partielle Deafferenzierung von Motoneuronen das funktionelle Outcome einer peripheren Nervenverletzung beeinträchtigen kann. Um die o. g. Hypothese zu überprüfen, wurde hier versucht die Deafferenzierung der Motoneurone nach Durchtrennung und Naht des Nervus femoralis der Ratte zu manipulieren. Zwei neuroaktive Moleküle, Botulinum-Neurotoxin A (BoNT) und Brain-derived neurotrophic factor (BDNF), die bekanntlich synaptische Eingänge an Neuronen beeinflussen, wurden als „Manipulationswerkzeuge“ ausgewählt. Die Effekte dieser Behandlungen auf das Outcome der Nervenregeneration wurden funktionell und strukturell untersucht. BoNT oder BDNF wurden an den proximalen Stumpf des durchtrennten Nervus femoralis appliziert, um ihre Aufnahme und den Transport zu den Perikarya sowie eventuell die Transzytose zu afferenten Synapsen zu erreichen. Als Kontrolle diente bovines Serumalbumin (BSA). Die Experimente wurden an erwachsenen, zehn Wochen alten weiblichen Wistar Ratten durchgeführt, die entweder eine BoNT (N = 17), BDNF (N = 15) oder BSA (N = 13) Behandlung erhielten. Nach der Applikation wurde der Nerv chirurgisch rekonstruiert und die funktionelle Erholung mithilfe eines etablierten Ganganalyseverfahrens in einem Zeitraum von fünf Monaten dokumentiert. Weitere Outcome-Parameter waren die Qualität der Endplattenreinnervation (Auftreten anormaler Polyinnervation) und die Anzahl der 8 cholinergen, GABA/glycinergen und glutamatergen synaptischen Terminale im motorischen Kern des N. femoralis im Rückenmark. Zwei bis 20 Wochen nach der Läsion war die funktionelle Erholung nach BoNT Applikation signifikant besser im Vergleich zu den anderen beiden Behandlungen. Der posttraumatische Verlust an perisomatischen cholinergen Synapsen zwei Monate nach der Operation war ebenso reduziert in BoNT-behandelten Tieren. Regressionsanalysen zeigten signifikante lineare Korrelationen zwischen Funktionsparametern und der Anzahl cholinerger Terminale. Die Qualität der Endplattenreinnervation wurde nicht durch die Behandlung mit BoNT oder BDNF beeinflusst. Die Effekte von BoNT beruhen, wie durch Nachweis von gespaltetem SNAP-25 in perisomatischen Nerventerminale angedeutet, möglicherweise auf BoNT Transzytose. Eine bessere Erhaltung der modulatorischen cholinergen Terminale, die für die normale Erregbarkeit von Motoneuronen von entscheidender Bedeutung sind, könnte wiederum einer verbesserten Erholung der Funktion bei mit BoNT behandelten Ratten zugrunde liegen Die Ergebnisse stützen die Hypothese, dass langanhaltende partielle Deafferenzierungen von Motoneuronen negative Auswirkungen auf die funktionelle Erholung nach Nervenläsionen haben können. Die intraneurale Anwendung von neuroaktiven Substanzen scheint ein vielversprechender Weg zu sein, um kausale Zusammenhänge zwischen synaptischer Plastizität und Wiederherstellung der Funktion zu analysieren. Es ist außerdem denkbar, dass sich der beschriebene Ansatz der Arzneimittelapplikation zu einer klinisch durchführbaren Therapie entwickeln kann, wenn weitere kontrollierte Tierversuche überzeugende Beweise für seine Sicherheit und Wirksamkeit liefern
Botulinum Neurotoxin Application to the Severed Femoral Nerve Modulates Spinal Synaptic Responses to Axotomy and Enhances Motor Recovery in Rats
No full textBotulinum neurotoxin A (BoNT) and brain-derived neurotrophic factor (BDNF) are known for their ability to influence synaptic inputs to neurons. Here, we tested if these drugs can modulate the deafferentation of motoneurons following nerve section/suture and, as a consequence, modify the outcome of peripheral nerve regeneration. We applied drug solutions to the proximal stump of the freshly cut femoral nerve of adult rats to achieve drug uptake and transport to the neuronal perikarya. The most marked effect of this application was a significant reduction of the axotomy-induced loss of perisomatic cholinergic terminals by BoNT at one week and two months post injury. The attenuation of the synaptic deficit was associated with enhanced motor recovery of the rats 2–20 weeks after injury. Although BDNF also reduced cholinergic terminal loss at 1 week, it had no effect on this parameter at two months and no effect on functional recovery. These findings strengthen the idea that persistent partial deafferentation of axotomized motoneurons may have a significant negative impact on functional outcome after nerve injury. Intraneural application of drugs may be a promising way to modify deafferentation and, thus, elucidate relationships between synaptic plasticity and restoration of function
Carbohydrate mimics promote functional recovery after peripheral nerve repair
No full textSimova O, Irintchev A, Mehanna A, et al. Carbohydrate mimics promote functional recovery after peripheral nerve repair. ANNALS OF NEUROLOGY. 2006;60(4):430-437.Objective: The outcome of peripheral nerve repair is often unsatisfactory, and efficient therapies are not available. We tested the therapeutic potential of functional mimics of the human natural killer cell glycan (3-sulfoglucuronyl beta 1-3 galactoside) (HNK-1) epitope, a carbohydrate indicated to favor specificity of motor reinnervation in mice. Methods: We applied a linear HNK-1 mimic peptide, scrambled peptide, or vehicle substances in polyethylene cuffs used to reconstruct the severed femoral nerves of adult mice. We used video-based motion analysis and morphological and tracing techniques to monitor the outcome of nerve repair. Results: After glycomimetic application, quadriceps muscle function recovered to 93% of normal within 3 months. Restoration of function was less complete (71-76%) in control groups. Better functional recovery was associated with larger motoneuron somata, better axonal myelination in the quadriceps nerve, and enhanced precision of target reinnervation. Lesion-induced death of motoneurons was reduced by 20 to 25%. The glycomimetic enhanced survival and neurite outgrowth of both mouse and human motoneurons in vitro by 30 to 75%. Application of a novel cyclic glycomimetic also enhanced functional recovery in vivo. Interpretation: The improved outcome of nerve repair after glycomimetic application may be attributed to neurotrophic effects. Our results hold promise for therapeutic use in humans
Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration
No full textPMCID: PMC3212532This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Low-level Laser Therapy (lllt) In Dystrophin-deficient Muscle Cells: Effects On Regeneration Capacity, Inflammation Response And Oxidative Stress
No full textConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The present study evaluated low-level laser therapy (LLLT) effects on some physiological pathways that may lead to muscle damage or regeneration capacity in dystrophin-deficient muscle cells of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD). Primary cultures of mdx skeletal muscle cells were irradiated only one time with laser and analyzed after 24 and 48 hours. The LLLT parameter used was 830 nm wavelengths at 5 J/cm2fluence. The following groups were set up: Ctrl (untreated C57BL/10 primary muscle cells), mdx (untreated mdx primary muscle cells), mdx LA 24 (mdx primary muscle cells - LLLT irradiated and analyzed after 24 h), and mdx LA 48 (mdx primary muscle cells - LLLT irradiated and analyzed after 48 h). The mdx LA 24 and mdx LA 48 groups showed significant increase in cell proliferation, higher diameter in muscle cells and decreased MyoD levels compared to the mdx group. The mdx LA 48 group showed significant increase in Myosin Heavy Chain levels compared to the untreated mdx and mdx LA 24 groups. The mdx LA 24 and mdx LA 48 groups showed significant increase in [Ca2+]i. The mdx group showed significant increase in H2O2 production and 4-HNE levels compared to the Ctrl group and LLLT treatment reduced this increase. GSH levels and GPx, GR and SOD activities increased in the mdx group. Laser treatment reduced the GSH levels and GR and SOD activities in dystrophic muscle cells. The mdx group showed significant increase in the TNF-α and NF-κB levels, which in turn was reduced by the LLLT treatment. Together, these results suggest that the laser treatment improved regenerative capacity and decreased inflammatory response and oxidative stress in dystrophic muscle cells, indicating that LLLT could be a helpful alternative therapy to be associated with other treatment for dystrophinopathies. © 2015 Macedo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.106CAPES, Conselho Nacional de Desenvolvimento Científico e TecnológicoCNPq, Conselho Nacional de Desenvolvimento Científico e TecnológicoConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Engel, A.G., Yamamoto, M., Fischbeck, K.H., Dystrophinopathies (1994) Myology, pp. 1133-1187. , Engel AG, Franzini-Armstrong C McGraw-Hill: New YorkAngelini, C., The role of corticosteroids in muscular dystrophy: A critical appraisal (2007) Muscle Nerve, 36, pp. 424-435. , PMID: 17541998Kumar, A., Boriek, A.M., Mechanical stress activates the nuclear factor-kappaB pathway in skeletal muscle fibers: A possible role in Duchenne muscular dystrophy (2003) FASEB J, 17, pp. 386-396. , PMID: 12631578Hodgetts, S., Radley, H., Davies, M., Grounds, M.D., Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNF alpha function with Etanercept in mdx mice (2006) Neuromuscul Disord, 16, pp. 591-602. , PMID: 16935507Collins, R.A., Grounds, M.D., The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice (2001) J Histochemistry Cytochem, 49, pp. 989-1001. , PMID: 11457927De Senzi, R.M.P., Ferretti, R., Moraes, L.H., Neto, H.S., Marques, M.J., Minatel, E., N-acetylcysteine treatment reduces TNF-alpha levels and myonecrosis in diaphragm muscle of mdx mice (2013) Clin Nutr, 32, pp. 472-475. , PMID: 22727548Messina, S., Bitto, A., Aguennouz, M., Vita, G.L., Polito, F., Irrera, N., The soy isoflavone genistein blunts nuclear factor kappa-B, MAPKs and TNF-alpha activation and ameliorates muscle function and morphology in mdx mice (2011) Neuromuscul Disord, 21, pp. 579-589. , PMID: 21658942Mauricio, A.F., Minatel, E., Santo Neto, H., Marques, M.J., Effects of fish oil containing eicosapentaenoic acid and docosahexaenoic acid on dystrophic mdx mice (2013) Clin Nutr, 32, pp. 636-642. , PMID: 23218947Moraes, L.H.R., Bollineli, R.C., Mizobuti, D.S., Silveira, L.R., Marques, M.J., Minatel, E., Effect of N-acetylcysteine plus deferoxamine on oxidative stress and inflammation in dystrophic muscle cells (2014) Redox RepTerrill, J.R., Boyatzis, A., Grounds, M.D., Arthur, P.G., Treatment with the cysteine precursor l-2-oxothiazolidine-4-carboxylate (OTC) implicates taurine deficiency in severity of dystropathology in mdx mice (2013) Int J Biochem Biol, 459, pp. 2097-2108Stergioulas, A., Stergioula, M., Aarskog, R., Lopes-Martins, R.A., Bjordal, J.M., Effects of low-level laser therapy and eccentric exercises in the treatment of recreational athletes with chronic achilles tendinopathy (2008) Am J Sports Med, 36, pp. 881-887. , PMID: 18272794Ferraresi, C., Hamblin, M.R., Parizotto, N.A., Low-level laser (light) therapy (LLLT) on muscle tissue: Performance, fatigue and repair benefited by the power of light (2012) Photonics Lasers Med, 1, pp. 267-286. , PMID: 23626925Aimbire, F., Albertini, R., Pacheco, M.T., Castro-Faria-Neto, H.C., Leonardo, P.S., Iversen, V.V., Low-level laser therapy induces dose-dependent reduction of TNFalpha levels in acute inflammation (2006) Photomed Laser Surg, 24, pp. 33-37. , PMID: 16503786Albertini, R., Aimbire, F., Villaverde, A.B., Silva, J.A., Jr., Costa, M.S., COX-2 mRNA expression decreases in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation after low level laser therapy (2007) Inflamm Res, 56, pp. 228-229. , PMID: 17607546De Almeida, P., Lopes-Martins, R.A., Tomazoni, S.S., Silva, J.A., Jr., De Carvalho, P.D.T., Bjordal, J.M., Low-level laser therapy improves skeletal muscle performance, decreases skeletal muscle damage and modulates mRNA expression of COX-1 and COX-2 in a dose-dependent manner (2011) Photochem Photobiol, 87, pp. 1159-1163. , PMID: 21749398Albertini, R., Aimbire, F.S., Correa, F.I., Ribeiro, W., Cogo, J.C., Antunes, E., Effects of different protocol doses of low power gallium-aluminum-arsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan induced rat paw ooedema (2004) J Photochem Photobiol B, 74, pp. 101-107. , PMID: 15157905Hemvani, N., Chitnis, D.S., Bhagwanani, N.S., Helium-neon and nitrogen laser irradiation accelerates the phagocytic activity of human monocytes (2005) Photomed Laser Surg, 23, pp. 571-574. , PMID: 16356149Luo, L., Sun, Z., Zhang, L., Li, X., Dong, Y., Liu, T.C., Effects of low-level laser therapy on ROS homeostasis and expression of IGF-1 and TGF-beta1 in skeletal muscle during the repair process (2013) Lasers Med Sci, 28, pp. 725-734. , PMID: 22714676Leal Junior, E.C., Lopes-Martins, R.A., De Almeida, P., Ramos, L., Iversen, V.V., Bjordal, J.M., Effect of low-level laser therapy (GaAs 904 nm) in skeletal muscle fatigue and biochemical markers of muscle damage in rats (2010) Eur J Appl Physiol, 108, pp. 1083-1088. , PMID: 20024577Rando, T.A., Blau, H.M., Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy (1994) J Cell Biol, 125, pp. 1275-1287. , PMID: 8207057Hu, W.P., Wang, J.J., Yu, C.L., Lan, C.C., Chen, G.S., Yu, H.S., Helium-neon laser irradiation stimulates cell proliferation through photostimulatory effects in mitochondria (2007) J Invest Dermatol, 127, pp. 2048-2057. , PMID: 17446900Buttke, T.M., McCubrey, J.A., Owen, T., Use of an aqueous soluble tetrazolium/formazan assay to measure viability and proliferation of lymphokine-dependent cell lines (1993) J Immunol Methods, 157, pp. 233-240. , PMID: 8423368Guatimosim, S., Guatimosim, C., Song, L.S., Imaging calcium sparks in cardiac myocytes (2011) Methods Mol Biol, 689, pp. 205-214. , PMID: 21153794Winterbourn, C.C., Hawkins, R.E., Brian, M., Carrell, R.W., The estimation of red cell superoxide dismutase activity (1975) J Lab Clin Med, 85, pp. 337-341. , PMID: 803541Anderson, M.E., Determination of glutathione and glutathione disulfide in biological samples (1985) Methods Enzymol, 113, pp. 548-555. , PMID: 4088074Yoshikawa, T., Naito, Y., Kishi, A., Tomii, T., Kaneko, T., Linuma, S., Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats (1993) Gut, 34, pp. 732-737. , PMID: 8314503Carlberg, I., Mannervik, B., Glutathione reductase (1985) Methods Enzymol, 113, pp. 484-490. , PMID: 3003504Yablonka-Reuveni, Z., Anderson, J.E., Satellite cells from dystrophic (mdx) mice display accelerated differentiation in primary cultures and in isolated myofibers (2006) Dev Dyn, 235, pp. 203-212. , PMID: 16258933Nakano, J., Kataoka, H., Sakamoto, J., Origuchi, T., Okita, M., Yoshimura, T., Low-level laser irradiation promotes the recovery of atrophied gastrocnemius skeletal muscle in rats (2009) Exp Physiol, 94, pp. 1005-1015. , PMID: 19525315Ben-Dov, N., Shefer, G., Irintchev, A., Wernig, A., Oron, U., Halevy, O., Low-energy laser irradiation affects satellite cell proliferation and differentiation in vitro (1999) Biochim Biophys Acta, 1448, pp. 372-380. , PMID: 9990289Shefer, G., Barash, I., Oron, U., Halevy, O., Low-energy laser irradiation enhances de novo protein synthesis via its effects on translation-regulatory proteins in skeletal muscle myoblasts (2003) Biochim Biophys Acta, 1593, pp. 131-139. , PMID: 12581857Culligan, K., Banville, N., Dowling, P., Ohlendieck, K., Drastic reduction of calsequestrin-like proteins and impaired calcium binding in dystrophic mdx muscle (2002) J Appl Physiol, 92, pp. 435-445. , PMID: 11796649Williams, D.A., Head, S.I., Bakker, A.J., Stephenson, D.G., Resting calcium concentrations in isolated skeletal muscle fibres of dystrophic mice (1990) J Physiol, 428, pp. 243-256. , PMID: 2231412Gailly, P., Boland, B., Himpens, B., Casteels, R., Gillis, J.M., Critical evaluation of cytosolic calcium determination in resting muscle fibres from normal and dystrophic (mdx) mice (1993) Cell Calcium, 14, pp. 473-483. , PMID: 8358771Head, S.I., Membrane potential, resting calcium and calcium transients in isolated muscle fibres from normal and dystrophic mice (1993) J Physiol, 469, pp. 11-19. , PMID: 8271194Pressmar, J., Brinkmeier, H., Seewald, M.J., Naumann, T., Rudel, R., Intracellular Ca2+ concentrations are not elevated in resting cultured muscle from Duchenne (DMD) patients and in MDX mouse muscle fibres (1994) Pflugers Arch, 426, pp. 499-505. , PMID: 8052519Breitbart, H., Levinshal, T., Cohen, N., Friedmann, H., Lubart, R., Changes in calcium transport in mammalian sperm mitochondria and plasma membrane irradiated at 633 nm (HeNe laser) (1996) J Photochem Photobiol B, 34, pp. 117-121. , PMID: 8810529Lubart, R., Friedmann, H., Levinshal, T., Lavie, R., Breitbart, H., Effect of light on calcium transport in bull sperm cells (1992) J Photochem Photobiol B, 15, pp. 337-341. , PMID: 1432397Disatnik, M.H., Dhawan, J., Yu, Y., Beal, M.F., Whirl, M.M., Franco, A.A., Evidence of oxidative stress in mdx mouse muscle: Studies of the pre-necrotic state (1998) J Neurol Sci, 161, pp. 77-84. , PMID: 9879685Rando, T.A., Disatnik, M.H., Yu, Y., Franco, A., Muscle cells from mdx mice have an increased susceptibility to oxidative stress (1998) Neuromuscul Disord, 8, pp. 14-21. , PMID: 9565986Lubart, R., Eichler, M., Lavi, R., Friedman, H., Shainberg, A., Low-energy laser irradiation promotes cellular redox activity (2005) Photomed Laser Surg, 23, pp. 3-9. , PMID: 15782024Abdel, S.E., Abdel-Meguid, I., Korraa, S., Markers of oxidative stress and aging in Duchene muscular dystrophy patients and the possible ameliorating effect of He:Ne laser (2007) Acta Myol, 26, pp. 14-21. , PMID: 17915565Huang, Y.Y., Nagata, K., Tedford, C.E., McCarthy, T., Hamblin, M.R., Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro (2013) J Biophotonics, 6, pp. 829-838. , PMID: 23281261Lim, W., Kim, J., Lim, C., Kim, S., Jeon, S., Karna, S., Effect of 635 nm light-emitting diode irratiation on intracellular superoxide anion scavenging independent of the cellular enzymatic antioxidant system (2012) Photomed Laser Surg, 30, pp. 451-459. , PMID: 22775489Whitehead, N.P., Yeung, E.W., Allen, D.G., Muscle damage in mdx (dystrophic) mice: Role of calcium and reactive oxygen species (2006) Clin Exp Pharmacol Physiol, 33, pp. 657-662. , PMID: 16789936Liu, X.G., Zhou, Y.J., Liu, T.C., Yuan, J.Q., Effects of low-level laser irradiation on rat skeletal muscle injury after eccentric exercise (2009) Photomed Laser Surg, 27, pp. 863-869. , PMID: 19697999Mesquita-Ferrari, R.A., Martins, M.D., Silva, J.A., Jr., Da Silva, T.D., Piovesan, R.F., Pavesi, V.C., Effects of low-level laser therapy on expression of TNF-alpha and TGF-beta in skeletal muscle during the repair process (2011) Lasers Med Sci, 26, pp. 335-340. , PMID: 21053039Rizzi, C.F., Mauriz, J.L., Freitas Correa, D.S., Moreira, A.J., Zettler, C.G., Filippin, L.I., Effects of low-level laser therapy (LLLT) on the nuclear factor (NF)-kappaB signaling pathway in traumatized muscle (2006) Lasers Surg Med, 38, pp. 704-713. , PMID: 16799998Leal-Junior, E.C., De Almeida, P., Tomazoni, S.S., De Carvalho, P.D.T., Lopes-Martins, R.A., Frigo, L., Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression (2014) PloS One, 9. , PMID: 24599021Oron, A., Oron, U., Sadeh, M., Low-level laser therapy during posnatal development modulates degeneretion and enhances regeneration processes in the hindlimb muscle of dystrophic mice (2014) Photomed Laser Surg, 32, pp. 606-611. , PMID: 2532950
