title: Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.
abstract: Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM.
authors.affiliation: Department of Clinical Neurosciences, Anne McLaren Laboratory, Wellcome Trust-MRC Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, Academic Neurosurgery Unit, University of Cambridge, Cambridge Biomedical Campus, West Forvie Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.
authors.forename: Rana S
authors.initials: RS
authors.lastname: Dhillon
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, CB2 0AH, UK.
authors.forename: John
authors.initials: J
authors.lastname: Parker
authors.affiliation: Department of Clinical Neurosciences, Anne McLaren Laboratory, Wellcome Trust-MRC Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, Academic Neurosurgery Unit, University of Cambridge, Cambridge Biomedical Campus, West Forvie Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.
authors.forename: Yasir A
authors.initials: YA
authors.lastname: Syed
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Edgley
authors.affiliation: Department of Clinical Neurosciences, Anne McLaren Laboratory, Wellcome Trust-MRC Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, Academic Neurosurgery Unit, University of Cambridge, Cambridge Biomedical Campus, West Forvie Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Young
authors.affiliation: Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Fawcett
authors.affiliation: College of Veterinary Medicine, Iowa State University, 1800 Christensen Drive, Ames, IA, 50011-1134, USA.
authors.forename: Nick D
authors.initials: ND
authors.lastname: Jeffery
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Clifford Allbutt Building, Cambridge Biomedical Campus, Cambridge, CB2 0AH, UK.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.affiliation: Department of Clinical Neurosciences, Anne McLaren Laboratory, Wellcome Trust-MRC Cambridge Stem Cell Institute, John van Geest Centre for Brain Repair, Academic Neurosurgery Unit, University of Cambridge, Cambridge Biomedical Campus, West Forvie Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK. mrk25@cam.ac.uk.
authors.forename: Mark R N
authors.initials: MR
authors.lastname: Kotter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001369:Axons / Q000473:pathology / Q000502:physiology*; D019299:Decompression, Surgical; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009457:Neuroglia / Q000473:pathology / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index; D013117:Spinal Cord Compression / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D055009:Spondylosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D013569:Synapses / Q000473:pathology / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016708:Synaptophysin; C569016:Syp protein, rat