There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C ( ). The diameter of axons and nerve fibers was larger in CS1 ( ) and CS14 ( ) than in C, and myelin sheath thickness was lower in all crushed groups ( ). There was no functional difference between CS1 and CS14 ( ). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. 1. Introduction Peripheral nerve injury promotes motor, autonomic, and sensory alterations in the region of the affected nerve, among which loss of function and progressive muscular atrophy stand out [1, 2]. Regeneration speed and subsequent functional recovery depend on the extension, nature, and degree of injury [3, 4]. In many cases morphological and functional recovery are not fully achieved [2], causing limitations in daily life and work activities [5], and may lead to early retirement due to functional disability. Several studies have investigated the effects of physical treatments on peripheral nerve regeneration and functional recovery, including phasic electrical stimulation [6–8], chronic low-frequency electrical stimulation [9, 10], ultrasound [11, 12], and physical exercise [8, 13–15]. Studies with rabbits after sciatic nerve crush showed that swimming exercise aids in both the removal of degenerated myelin and in its synthesis during nerve regeneration [16]. Physical exercise results in increased nerve impulse conduction speed and sensory-motor recovery [13] as well as in muscle property maintenance, assisting in trophism and minimizing muscle weakness after denervation [17]. However, there is no consensus on the ideal time to start exercise after denervation. Considering that muscular reinnervation begins on the 14th day after injury, Herbinson et al. [18, 19] recommend that the stimulation of neuromuscular activity by exercise should begin approximately two weeks after nerve injury, leaving a rest period between the injury and the beginning of exercise. Gordon et al. [20] emphasized that, depending on the extent of the injury, exercise during the acute phase may
S. K. Lee and S. W. Wolfe, “Peripheral nerve injury and repair,” Journal of the American Academy of Orthopaedic Surgeons, vol. 8, no. 4, pp. 243–253, 2000.
E. Verdú, D. Ceballos, J. J. Vilches, and X. Navarro, “Influence of aging on peripheral nerve function and regeneration,” Journal of the Peripheral Nervous System, vol. 5, no. 4, pp. 191–208, 2000.
A. Eberstein and S. Eberstein, “Electrical stimulation of denervated muscle: is it worthwhile?” Medicine and Science in Sports and Exercise, vol. 28, no. 12, pp. 1463–1469, 1996.
A. C. Mendon？a, C. H. Barbieri, and N. Mazzer, “Directly applied low intensity direct electric current enhances peripheral nerve regeneration in rats,” Journal of Neuroscience Methods, vol. 129, no. 2, pp. 183–190, 2003.
N. Uzun, T. Tanriverdi, F. K. Savrun et al., “Traumatic peripheral nerve injuries: demographic and electrophysiologic findings of 802 patients from a developing country,” Journal of Clinical Neuromuscular Disease, vol. 7, no. 3, pp. 97–103, 2006.
M. L. O. Polacow, C. A. Silva, R. R. J. Guirro, M. R. Campos, and J. P. Borges, “Estudo morfométrico do músculo sóleo desnervado de ratos tratados pela associa？？o de metformina e estimula？？o elétrica,” Revista Brasileira de Fisioterapia, vol. 7, no. 1, pp. 77–84, 2003.
K. C. B. G. Fernandes, M. L. O. Polacow, R. R. J. Guirro, et al., “Análise morfométrica dos tecidos muscular e conjuntivo após denerva？？o e estimula？？o elétrica de baixa freqüência,” Revista Brasileira de Fisioterapia, vol. 9, no. 2, pp. 235–241, 2005.
L. S. Oliveira, L. L. Sobral, S. Y. M. Takeda et al., “Estimulación eléctrica y natación en la fase aguda de la axonotmesis: influencia sobre la regeneración nerviosa y la recuperación funcional,” Revista de Neurologia, vol. 11, no. 1, pp. 11–15, 2008.
D. E. Dow, J. A. Faulkner, and R. G. Dennis, “Distribution of rest periods between electrically generated contractions in denervated muscles of rats,” Artificial Organs, vol. 29, no. 6, pp. 432–435, 2005.
A. R. Crisci and A. L. Ferreira, “Low-intensity pulsed ultrasound accelerates the regeneration of the sciatic nerve after neurotomy in rats,” Ultrasound in Medicine and Biology, vol. 28, no. 10, pp. 1335–1341, 2002.
V. V. Monte-Raso, C. H. Barbieri, N. Mazzer, and V. P. S. Fazan, “Os efeitos do ultra-som terapêutico nas les？es por esmagamento do nervo ciático de ratos: análise funcional da marcha,” Revista Brasileira de Fisioterapia, vol. 10, no. 1, pp. 113–119, 2006.
N. L. U. Van Meeteren, J. H. Brakkee, F. P. T. Hamers, P. J. M. Helders, and W. H. Gispen, “Exercise training improves functional recovery and motor nerve conduction velocity after sciatic nerve crush lesion in the rat,” Archives of Physical Medicine and Rehabilitation, vol. 78, no. 1, pp. 70–77, 1997.
Y. H. Byun, M. H. Lee, S. S. Kim et al., “Treadmill running promotes functional recovery and decreases brain-derived neurotrophic factor mRNA expression following sciatic crushed nerve injury in rats,” Journal of Sports Medicine and Physical Fitness, vol. 45, no. 2, pp. 222–228, 2005.
L. L. Sobral, L. S. Oliveira, S. Y. M. Takeda, M. C. Somazz, M. I. L. Montebelo, and R. M. Teodori, “Immediate versus later exercises for rat sciatic nerve regeneration after axonotmesis: histomorphometric and functional analyses,” Revista Brasileira de Fisioterapia, vol. 12, no. 4, pp. 311–316, 2008.
L. Sarikcioglu and N. Oguz, “Exercise training and axonal regeneration after sciatic nerve injury,” International Journal of Neuroscience, vol. 109, no. 3-4, pp. 173–177, 2001.
S. Possebon, R. Iorczeski, A. C. Giacomini, F. L. Giacomini, and V. R. Haas, “Efeitos do Treinamento físico e da Creatina Magnésio em músculos desnervados de Ratos,” Revista Médica HSVP, vol. 13, no. 29, pp. 16–21, 2001.
G. J. Herbinson, M. M. Jaweed, and J. F. Ditunno, “Effects of swimming on reinnervation of rat skeletal muscle,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 37, pp. 1247–1251, 1974.
G. J. Herbinson, M. M. Jaweed, and J. F. Ditunno, “Reinnervating rat skeletal muscle: effect of 35% grade treadmill exercise,” Archives of Physical Medicine and Rehabilitation, vol. 63, no. 7, pp. 313–316, 1982.
T. Gordon, O. Sulaiman, and G. Boyd, “Increase neuromuscular activity reduces sprouting in partially denervated muscles,” Journal of Neuroscience, vol. 21, no. 2, pp. 654–667, 2001.
T. Marqueste, J. R. Alliez, O. Alluin, Y. Jammes, and P. Decherchi, “Neuromuscular rehabilitation by treadmill running or electrical stimulation after peripheral nerve injury and repair,” Journal of Applied Physiology, vol. 33, no. 9, pp. 492–501, 2004.
T. B. Seo, I. S. Han, J. H. Yoon, K. E. Hong, S. J. Yoon, and U. K. Namgung, “Involvement of Cdc2 in axonal regeneration enhanced by exercise training in rats,” Medicine and Science in Sports and Exercise, vol. 38, no. 7, pp. 1267–1276, 2006.
F. A. Voltarelli, C. A. Gobatto, and M. A. R. Mello, “Determination of anaerobic threshold in rats using the lactate minimum test,” The Brazilian Journal of Medical and Biological Research, vol. 35, no. 11, pp. 1389–1394, 2002.
C. A. Gobatto, M. A. R. Mello, C. Y. Sibuya, J. R. M. Azevedo, L. A. Santos, and E. Kokubun, “Maximal lactate steady state in rats submitted to swimming exercise,” Comparative Biochemistry and Physiology, vol. 130, no. 1, pp. 21–27, 2001.
E. Gutmann and B. Jakoubek, “Effect of increased motor activity on regeneration of the peripheral nerve in young rats,” Physiologia Bohemoslovenica, vol. 12, pp. 463–468, 1963.
N. Ueno, S. Oh-ishi, T. Kizaki, M. Nishida, and H. Ohno, “Effects of swimming training on brown-adipose tissue activity in obese ob/ob mice: GDP binding and UCP m-RNA expression,” Research Communications in Molecular Pathology and Pharmacology, vol. 95, no. 1, pp. 92–104, 1997.
L. De Medinacelli, W. J. Freed, and R. J. Wyatt, “An index of the function condition of rat sciatic nerve based on measurements made from walking tracks,” Experimental Neurology, vol. 77, pp. 6634–6643, 1982.
A. S. Varej？o, P. Melo-Pinto, M. F. Meek, V. M. Filipe, and J. Bulas-Cruz, “Methods for the experimental functional assessment of rat sciatic nerve regeneration,” Neurological Research, vol. 26, no. 2, pp. 186–194, 2004.
J. R. Bain, S. E. Mackinnon, and D. A. Hunter, “Functional evaluation of complete sciatic, peroneal and posterior tibial nerve lesions in the rat,” Plastic and Reconstructive Surgery, vol. 83, no. 1, pp. 129–138, 1989.
M. J. Karnovsky, “A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy,” The Journal of Cell Biology, vol. 27, p. 137a, 1965.
A. Gorio, G. Carmignoto, M. Finesso, P. Polato, and M. G. Nunzi, “Muscle reinnervation. II. Sprouting, synapse formation and repression,” Neuroscience, vol. 8, no. 3, pp. 403–416, 1983.
M. Favero, E. Lorenzetto, C. Bidoia, M. Buffelli, G. Busetto, and A. Cangiano, “Synapse formation and elimination: role of activity studied in different models of adult muscle reinnervation,” Journal of Neuroscience Research, vol. 85, no. 12, pp. 2610–2619, 2007.
J. Fraher and P. Dockery, “A strong myelin thickness-axon size correlation emerges in developing nerves despite independent growth of both parameters,” Journal of Anatomy, vol. 193, no. 2, pp. 195–201, 1998.
D. E. Schroder, “Altered ratio between axon diameter and myelin shealth thickness in regenerated nerve fibers,” Brain Research, vol. 193, pp. 562–565, 1972.
A. D. Ansselin, T. Fink, and D. F. Davey, “Peripheral nerve regeneration through nerve guides seeded with Schwann cells,” Neuropathology and Applied Neurobiology, vol. 23, pp. 387–398, 1997.
O. A. R. Sulaiman and T. Gordon, “Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination and size,” Glia, vol. 32, no. 3, pp. 234–246, 2000.
S. Torch, Y. Usson, and R. Saxod, “Automated morphometric study of human peripheral nerves by image analysis,” Pathology Research and Practice, vol. 185, no. 5, pp. 567–571, 1989.
H. Dash, A. Kononov, R. A. Prayson, S. Petras, and E. Z. Browne, “Evaluation of nerve recovery from minimal-duration crush injury,” Annals of Plastic Surgery, vol. 37, no. 5, pp. 526–531, 1996.
G. Carmignoto, M. Finesso, R. Siliprandi, and A. Gorio, “Muscle reinnervation. I. Restoration of transmitter release mechanisms,” Neuroscience, vol. 8, no. 3, pp. 393–401, 1983.
H. H. Ehrsson, A. Fagergren, T. Jonsson, G. Westling, R. S. Johansson, and H. Forssberg, “Cortical activity in precision-versus power-grip tasks: an fMRI study,” Journal of Neurophysiology, vol. 83, no. 1, pp. 528–536, 2000.
A. Bodeg？rd, S. Geyer, E. Naito, K. Zilles, and P. E. Roland, “Somato-sensory areas in man activated by moving stimuli,” NeuroReport, vol. 11, no. 1, pp. 187–191, 2000.
M. G. Shuler, D. J. Krupa, and M. A. Nicolelis, “Bilateral integration of whisker information in the primary somatosensory cortex of rats,” Journal of Neuroscience, vol. 21, no. 14, pp. 5251–5261, 2001.
J. Munn, R. D. Herbert, and S. C. Gandevia, “Contralateral effects of unilateral resistance training: a meta-analysis,” Journal of Applied Physiology, vol. 96, no. 5, pp. 1861–1866, 2004.
R. Kristeva, D. Cheyne, and L. Deecke, “Neuromagnetic fields accompanying unilateral and bilateral voluntary movements: topography and analysis of cortical sources,” Electroencephalography and Clinical Neurophysiology, vol. 81, no. 4, pp. 284–298, 1991.
T. Hortobágyi, “Cross Education and the human central nervous system: mechanisms of unilateral interventions producing contralateral adaptations,” IEEE Engineering in Medicine and Biology Magazine, vol. 24, no. 1, pp. 22–28, 2005.
M. M. Merzenich, J. H. Kaas, J. T. Wall, M. Sur, R. J. Nelson, and D. J. Felleman, “Progression of change following median nerve section in the cortical representation of the hand in areas 3b and 1 in adult owl and squirrel monkeys,” Neuroscience, vol. 10, no. 3, pp. 639–665, 1983.
J. T. Wall, D. J. Felleman, and J. H. Kaas, “Recovery of normal topography in the somatosensory cortex of monkeys after nerve crush and regeneration,” Science, vol. 221, no. 4612, pp. 771–773, 1983.
J. T. Trachtenberg, B. E. Chen, G. W. Knott et al., “Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex,” Nature, vol. 420, no. 6917, pp. 788–794, 2002.
O. Hudlická, L. Dodd, E. M. Renkin, and S. D. Gray, “Early changes in fiber profile and capillary density in long-term stimulated muscles,” The American Journal of Physiology, vol. 243, no. 4, pp. 528–535, 1982.
C. A. Silva, R. R. J. Guirro, M. L. O. Polacow, H. C. Silva, A. P. Tanno, and D. Rodrigues, “Efeito da metformina e eletroestimula？？o sobre as reserves de glicogênio do músculo sóleo normal e desnervado,” Revista Brasileira de Fisioterapia, vol. 21, no. 3, pp. 55–60, 1999.
V. Aas, S. Torbla, M. H. Andersen, J. Jensen, and A. C. Rustan, “Electrical stimulation improves insulin responses in a human skeletal muscle cell model of hyperglycemia,” Annals of the New York Academy of Sciences, vol. 967, pp. 506–515, 2002.
