Background: G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims: The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods: Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results: Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions: The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. MDX dystrophic mice present a decreased peripheral nerve regeneration, secondarily to muscle degeneration. G-CSF treatment increases motor function in MDX mice, by increasing axonal regrowth and Schwann cell activity.45738753Avalos, B.R., Molecular analysis of the granulocyte colony-stimulating factor receptor (1996) Blood, 88, pp. 761-777Belkas, J.S., Shoichet, M.S., Midha, R., Peripheral nerve regeneration through guidance tubes (2004) Neurol. Res., 26, pp. 151-160Boneberg, E.M., Hareng, L., Gantner, F., Wendel, A., Hartung, T., Human monocytes express functional receptors for granulocyte colonystimulating factor that mediate suppression of monokines and interferon-gamma (2000) Blood, 95, pp. 270-276Bozkurt, A., Brook, G.A., Moellers, S., Lassner, F., Sellhaus, B., Weis, J., In vitro assessment of axonal growth using dorsal root ganglia explants in a novel three-dimensional collagen matrix (2007) Tissue Eng., 13, pp. 2971-2979Chen, Z.L., Yu, W.M., Strickland, S., Peripheral regeneration (2007) Annu. Rev. Neurosci., 30, pp. 209-233Deconinck, N., Dan, B., Pathophysiology of duchenne muscular dystrophy: current hypotheses (2007) Pediatr. Neurol., 36, pp. 1-7Demetri, G.D., Griffin, J.D., Granulocyte colony-stimulating factor and its receptor (1999) Blood, 78, pp. 2791-2808Deumens, R., Jaken, R.J., Marcus, M.A., Joosten, E.A., The CatWalk gait analysis in assessment of both dynamic and static gait changes after adult rat sciatic nerve resection (2007) J. Neurosci. Methods, 16, pp. 120-130Hamers, F.P., Koopmans, G.C., Joosten, E.A., CatWalk-assisted gait analysis in the assessment of spinal cord injury (2006) J. Neurotrauma, 23, pp. 537-548Hara, M., Yausa, S., Shimoji, K., Onizuka, T., Hayashiji, N., Ohno, Y., G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation (2011) J. Exp. Med., 208, pp. 715-727Harada, M., Qin, Y., Takano, H., Minamino, T., Zou, Y., Toko, H., G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes (2005) Nat. Med., 11, pp. 305-311Ikeda, M., Oka, Y., The relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration (2012) Brain Behav., 2, pp. 382-390Kawada, H., Takizawa, S., Takanashi, T., Morita, Y., Fujita, J., Fukuda, K., Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells (2006) Circulation, 113, pp. 701-710Lee, S.T., Chu, K., Jung, K.H., Ko, S.Y., Kim, E.H., Sinn, D.I., Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia (2005) Brain Res., 1058, pp. 120-128Levi, A.D., Bunge, R.P., Studies of myelin formation after transplantation of human Schwann cells into the severe combined immunodeficient mouse (1994) Exp. Neurol., 130, pp. 41-52Lyons, P.R., Slater, C.R., Structure and function of the neuromuscular junction in young adult mdx mice (1991) J. Neurocytol., 20, pp. 969-981Mayhew, T.M., Sharma, A.K., Sampling schemes for estimating nerve fibre size. II. Methods for unifascicular nerve trunks (1984) J. Anat., 139 (Pt 1), pp. 59-66de Medinaceli, L., Freed, W.J., Wyatt, R.J., An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks (1982) Exp. Neurol., 77, pp. 634-643Meek, M.F., Den Dunnen, W.F., Schakenraad, J.M., Robinson, P.H., Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly (dl-lactide-epsilon-caprolactone) nerve guide, using walking track analysis and electrostimulation tests (1999) Microsurgery, 19, pp. 247-253Metcalf, D., Hematopoietic cytokines (2008) Blood, 111, pp. 485-491Mirski, R., Reichert, F., Klar, A., Rotshenker, S., Granulocyte macrophage colony stimulating factor (GM-CSF) activity is regulated by a GM-CSF binding molecule in Wallerian degeneration following injury to peripheral nerve axons (2003) J. Neuroimmunol., 140, pp. 88-96Nagel, A., Lehmann-Horn, F., Engel, A.G., Neuromuscular transmission in the mdx mouse (1990) Muscle Nerve, 13, pp. 742-749Naito, T., Goto, K., Morioka, S., Matsuba, Y., Akema, T., Sugiura, T., Administration of granulocyte colony-stimulating factor facilitates the regenerative process of injured mice skeletal muscle via the activation of Akt/GSK3alphabeta signals (2009) Eur. J. Appl. Physiol., 105, pp. 643-651Okada, H., Takemura, G., Li, Y., Ohno, T., Li, L., Maruyama, R., Effect of a long-term treatment with a low-dose granulocyte colony-stimulating factor on post-infarction process in the heart (2008) J. Cell Mol. Med., 12, pp. 1272-1283Oliveira, A.L., Langone, F., Non-neuronal cells are not the limiting factor for the low axonal regeneration in C57BL/6J mice (2000) Braz. J. Med. Biol. Res., 33, pp. 1467-1475Pastoret, C., Sebille, A., MDX mice show progressive weakness and muscle deterioration whith age (1995) J. Neurol. Sci., 129, pp. 97-105Pfister, L.A., Papaloizos, M., Merkle, H.P., Gander, B., Nerve conduits and growth factor delivery in peripheral nerve repair (2007) J. Peripher. Nerv. Syst., 12, pp. 65-82Pierucci, A., de Duek, E.A., de Oliveira, A.L., Peripheral nerve regeneration through biodegradable conduits prepared using solvent evaporation (2008) Tissue Eng. Part A, 14, pp. 595-606Pitzer, C., Krüger, C., Plaas, C., Kirsch, F., Dittgen, T., Müller, R., Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis (2008) Brain, 131 (Pt 12), pp. 3335-3347Pollari, E., Savchenko, E., Jaronen, M., Kanninen, K., Malm, T., Wojciechowski, S., Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis (2011) J. Neuroinflammation, 28, p. 74Rushton, W.A., A theory of the effects of fibre size in medullated nerve (1951) J. Physiol., 115, pp. 101-122Saito, M., Kiyokawa, N., Taguchi, T., Suzuki, K., Sekino, T., MimorI, K., Granulocyte colony-stimulating factor directly affects human monocytes and modulates cytokine secretion (2002) Exp. Hematol., 30, pp. 1115-1123Schneider, A., Kruger, C., Steigleder, T., Weber, D., Pitzer, C., Laage, R., The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis (2005) J. Clin. Invest., 115, pp. 2083-2098Shyu, W.C., Lin, S.Z., Yang, H.I., Tzeng, Y.S., Pang, C.Y., Yen, P.S., Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells (2004) Circulation, 110, pp. 1847-1854Simões, G.F., Oliveira, A.L.R., Alpha motoneurone input changes in dystrophic MDX mice after sciatic nerve transection (2010) Neuropathol. Appl. Neurobiol., 36, pp. 55-70Simões, G.F., Oliveira, A.L.R., Synaptic Changes at the Spinal Cord Level and Peripheral Nerve Regeneration During the Course of Muscular Dystrophy in MDX Mice (2012), http://www.intechopen.com/books/muscular-dystrophy/synaptic-changes-at-the-spinal-cord-level-and-peripheral-nerve-regeneration-during-the-course-of-musc, Muscular Dystrophy, Dr. Madhuri Hegde (Ed.) Available from: , InTechSimões, G.F., Oliveira, A.L.R., Granulocyte-colony stimulating factor improves MDX mouse response to peripheral nerve injury (2012) PLoS One, 7, p. e42803Smith, R.S., Koles, Z.J., Myelinated nerve fibers: computed effect of myelin thickness on conduction velocity (1970) Am. J. Physiol., 219, pp. 1256-1258Stoll, G., Muller, H.W., Nerve injury, axonal degeneration and neural regeneration: basic insights (1999) Brain Pathol., 9, pp. 313-325Stratos, I., Rotter, R., Eipel, C., Mittlmeier, T., Vollmar, B., Granulocyte-colony stimulating factor enhances muscle proliferation and strength following skeletal muscle injury in rats (2007) J. Appl. Physiol., 103, pp. 1857-1863Varejão, A.S., Cabrita, A.M., Meek, M.F., Bulas-Cruz, J., Melo-Pinto, P., Raimondo, S., Functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp (2004) J. Neurotrauma, 21, pp. 1652-1670Vleggeert-Lankamp, C.L., The role of evaluation methods in the assessment of peripheral nerve regeneration through synthetic conduits: a systematic review. Laboratory investigation (2007) J. Neurosurg., 107, pp. 8-89Waller, A., Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog and observations on the alterations produced thereby in the structure of their primitive fibers (1850) Phil. Trans. R. Soc. Lond. Biol., 40, pp. 423-429Wang, H., Spinner, R.J., Sorenson, E.J., Windebank, A.J., Measurement of forelimb function by digital video motion analysis in rat nerve transection models (2008) J. Peripher. Nerv. Syst., 12, pp. 92-102Waxman, S.G., Determinants of conduction velocity in myelinated nerve fibers (1980) Muscle Nerve, 3, pp. 141-150Welte, K., Gabrilove, J., Bronchud, M.H., Platzer, E., Morstyn, G., Filgrastim (r-metHuG-CSF): the first 10 years (1996) Blood, 88, pp. 1907-1929Xin, L., Richardson, P.M., Gervais, F., Skamene, E., A deficiency of axonal regeneration in C57BL/6J mice (1990) Brain Res., 510, pp. 144-146Zaruba, M.M., Theiss, H.D., Vallaster, M., Mehl, U., Brunner, S., David, R., Synergy between CD26/DPP-IV inhibition and G-CSF improves cardiac function after acute myocardial infarction (2009) Cell Stem Cell, 4, pp. 313-323