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UBC Theses and Dissertations

Characterization of oligodendrocyte lineage cell responses remote to the lesion site in a murine model of thoracic contusion spinal cord injury (SCI) Moulson, Aaron Jack Taylor


Traumatic injury to the adult mammalian central nervous system (CNS) commonly results in permanent functional impairment due to the inability of injured CNS neurons to mount an effective regenerative response. Injury to the spinal cord is associated with a range of sensory, motor, and autonomic deficits, the most severe of which is complete paralysis. At a histological level, injury induced pathophysiological processes have been thoroughly characterized for the tissue area immediately surrounding the lesion epicentre, however remote to the lesion these changes are less well described. Previous studies have demonstrated that various perturbations, including traumatic injury, demyelination, artificial neural stimulation, neurodegeneration, and social experience, among others, induce robust oligodendrocyte precursor cells (OPC) responses, which function as endogenous precursors for myelinating oligodendrocytes. De novo myelination in the adult CNS has been implicated in motor learning, memory, and optimization of neural network function, thought to represent a potent form of neural plasticity. The demonstration of robust OPC proliferation and oligodendrogenesis in models of dorsal rhizotomy, axotomy, and axon degeneration, combined with the robust OPC responses characteristic of SCI lesion epicentres, lead us to hypothesize that contusion SCI would induce significant responses in resident OPC populations remote to the lesion site (specifically comprised of OPC proliferation, oligodendrogenesis, and new myelination). This may be functionally relevant to myelin plasticity on spared motor and sensory tracts remote to the lesion. To test this hypothesis, we conducted an in vivo study employing transgenic mouse lines (i.e. PDGFRα-CreERT:ROSA26-YFP and PDGFRα-CreERT:ROSA26-mGFP) that enabled the visualization and fate-mapping of OPCs and their progeny in the adult murine spinal cord following a moderate (70 Kdyne) T9-T10 thoracic contusion injury. Consistent with our predictions, we observed robust OPC proliferation and oligodendrogenesis remote to the lesion in both the cervical and lumbar spinal cord. Surprisingly, this did not manifest as increased new myelination, attributed (at least in part) to an observed maturation impairment of newly-formed oligodendrocytes.

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