title: The impact of myelination on axon sparing and locomotor function recovery in spinal cord injury assessed using diffusion tensor imaging.
abstract: The dysmyelinated axons of shiverer mice exhibit impaired conduction characteristics, similar to early postnatal axons before myelination, whereas the patterns of neuronal activity and connectivity are relatively comparable with those of wild-type myelinated axons. This unique dysmyelination pattern is exploited in the present study to determine the role of compact myelin in the loss and recovery of function following traumatic spinal cord injury (SCI). We applied in vivo diffusion tensor imaging (DTI) and post-mortem immunohistochemistry analysis to examine changes in myelin and axonal integrity, and evaluated these changes in concert with the analysis of locomotor function from 1 to 4 weeks following a mid-thoracic contusion injury in homozygous shiverer and heterozygous littermate mice. The DTI biomarkers, axial and radial diffusivities, are noninvasive indicators of axon and myelin integrity in response to SCI of both myelinated and dysmyelinated spinal cord. We show that myelin is critical for normal hind limb function in open field locomotion. However, when the functional outcome is limited during chronic SCI, the extent of recovery is associated with residual axonal integrity and independent of the extent of intact myelin at the lesion epicenter.
authors.affiliation: Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, MO, USA.
authors.forename: Tsang-Wei
authors.initials: TW
authors.lastname: Tu
authors.forename: Joong H
authors.initials: JH
authors.lastname: Kim
authors.forename: Feng Qin
authors.initials: FQ
authors.lastname: Yin
authors.forename: Lyn B
authors.initials: LB
authors.lastname: Jakeman
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D016880:Anisotropy; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006579:Heterozygote; D051379:Mice; D008818:Mice, Neurologic Mutants; D009043:Motor Activity; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013194:Staining and Labeling; D013997:Time Factors
chemical_list: D004676:Myelin Basic Protein; D016900:Neurofilament Proteins
keywords: diffusion tensor imaging; dysmyelination; myelin; spinal cord injury; white matter