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Journal article
Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes
Experimental neurology, v 276, pp 72-82
Feb 2016
PMCID: PMC4715943
PMID: 26366525
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Insufficient regeneration of central nervous system (CNS) axons contributes to persisting neurological dysfunction after spinal cord injury (SCI). Peripheral nerve grafts (PNGs) support regeneration by thousands of injured intraspinal axons and help them bypass some of the extracellular barriers that form after SCI. However this number represents but a small portion of the total number of axons that are injured. Here we tested if rhythmic sensory stimulation during cycling exercise would boost the intrinsic regenerative state of neurons to enhance axon regeneration into PNGs after a lower thoracic (T12) spinal transection of adult rats. Using True Blue retrograde tracing, we show that 4weeks of cycling improves regeneration into a PNG from lumbar interneurons but not by primary sensory neurons. The majority of neurons that regenerate their axon are within 5mm of the lesion and their number increased 70% with exercise. Importantly propriospinal neurons in more distant regions (5–20mm from the lesion) that routinely exhibit very limited regeneration responded to exercise by increasing the number of regenerating neurons by 900%. There was no exercise-associated increase in regeneration from sensory neurons. Analyses using fluorescent in situ hybridization showed that this increase in regenerative response is associated with changes in levels of mRNAs encoding the regeneration associated genes (RAGs) GAP43, β-actin and Neuritin. While propriospinal neurons showed increased mRNA levels in response to SCI alone and then to grafting and exercise, sensory neurons did not respond to SCI, but there was a response to the presence of a PNG. Thus, exercise is a non-invasive approach to modulate gene expression in injured neurons leading to an increase in regeneration. This sets the stage for future studies to test whether exercise will promote axon outgrowth beyond the PNG and reconnection with spinal cord neurons, thereby demonstrating a potential clinical application of this combined therapeutic intervention.
•Peripheral nerve grafts support CNS regeneration after SCI.•Post-injury exercise increases regeneration into peripheral nerve grafts.•Regenerative effort is correlated with the levels of regeneration-associated mRNAs.•Propriospinal but not sensory neurons respond to exercise.•Data suggest exercise as a therapy to promote regeneration after SCI.
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Details
- Title
- Exercise dependent increase in axon regeneration into peripheral nerve grafts by propriospinal but not sensory neurons after spinal cord injury is associated with modulation of regeneration-associated genes
- Creators
- Rahul Sachdeva - Drexel UniversityCatherine C. Theisen - Drexel UniversityVinu Ninan - Drexel UniversityJeffery L. Twiss - University of South CarolinaJohn D. Houlé - Drexel University
- Publication Details
- Experimental neurology, v 276, pp 72-82
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000369470400009
- Scopus ID
- 2-s2.0-84954377341
- Other Identifier
- 991019168432304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences