Exercise enhances axonal growth and functional recovery in the regenerating spinal cord

Doyle, Louise; Roberts, Barry L.

doi:10.1016/j.neuroscience.2006.03.044

Cited by 31 publications

(21 citation statements)

References 63 publications

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“…Accordingly, exercise has been suggested to display enhanced action on regeneration when axons undergo outgrowth [2]. Our current findings underscore this idea showing that SC transplantation and FGF-2 gene transfer likely increase the susceptibility of axons to exercise.…”

Section: Summary and Discussionsupporting

confidence: 78%

The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps

Haastert

Ying

Grothe

et al. 2008

Neuroscience Letters

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Studies were conducted to determine the possibility that voluntary exercise could enhance regenerative effects of gene therapy via Schwann cells (SC) over-expressing FGF-2. Sedentary or exercise rehabilitation conditions were therefore provided shortly after reconstructing 10 mm sciatic nerve gaps in rats with silicone grafts. Exercise for 7 days elevated mRNA levels of regeneration associated proteins (GAP-43 and synapsin I) in lumbar spinal cord and dorsal root ganglia of SC transplanted, in contrast to non-cellular reconstructed rats. FGF-2 gene therapy followed by 25-27 days of exercise did enhance regeneration of myelinated axons in comparison to sedentary animals. Four weeks after surgery mRNA levels of regeneration associated proteins were significantly higher in lumbar spinal cord of running compared to sedentary SC transplanted animals. Our results suggest that voluntary exercise could reinforce the beneficial effects of SC transplantation and FGF-2 gene therapy in peripheral nerve reconstruction approaches.

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Section: Summary and Discussionsupporting

confidence: 78%

The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps

Haastert

Ying

Grothe

et al. 2008

Neuroscience Letters

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“…In recent years, there has been a growing interest in evaluating the remote effects of exercise on various neurological conditions, including peripheral [10], [14], [15] and central [16]–[18] nervous system injury (reviewed in [19], [20]). Here we report the effects of regular treadmill exercise on peripheral nerve regeneration in a model of peripheral nerve repair that shows good correlation between the numbers of axons that regenerate and behavioral functional outcome measures used.…”

Section: Discussionmentioning

confidence: 99%

Treadmill Exercise Induced Functional Recovery after Peripheral Nerve Repair Is Associated with Increased Levels of Neurotrophic Factors

Park

Höke

2014

PLoS ONE

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Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF), brain derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

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“…Hind limb muscle fibres and lumbar astrocytes have been found to produce HSP70, a stress protein that could also act as a neurotrohic factor critically involved in motoneuron survival (Robinson et al 2005). Exercise is known to stimulate the regenerative potential of CNS neurons (Doyle & Roberts, 2006), restore neurotrophic factor levels and synaptic plasticity (Ying et al 2005), and promote a permissive cellular environment for axonal growth (Ghiani et al 2007) following SCI. In carrying out these tasks, exercise mimics and possibly potentiates the effects of OEG transplants on neuronal regeneration and synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Slow‐ and fast‐twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

Negredo

Rivero

González

et al. 2008

The Journal of Physiology

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Paralysed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 months after the intervention and compared with non-transplanted SCT rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (-0.843, P < 0.0001) and the fraction of variant 2s of the slow regulatory myosin light chain isoform (0.848, P < 0.0001) in SOL. Despite the mean overall effect of OEG transplants in patterning skeletal muscle protein expression towards normal, in 6 out of 9 animals they appeared insufficient to overcome fibre type switching and to support a consistent and generalized long-term maintenance of normal skeletal muscle characteristics. The interplay of OEG and exercise-mediated neurotrophic actions is a plausible mechanism underlying OEG transplantation effects on paralysed skeletal muscle.

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Exercise enhances axonal growth and functional recovery in the regenerating spinal cord

Cited by 31 publications

References 63 publications

The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps

The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps

Treadmill Exercise Induced Functional Recovery after Peripheral Nerve Repair Is Associated with Increased Levels of Neurotrophic Factors

Slow‐ and fast‐twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

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