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UBC Theses and Dissertations

The role of oligodendrocyte remyelination in locomotor recovery after traumatic spinal cord injury Manesh, Sohrab


Remyelination occurs after spinal cord injury (SCI) but its functional relevance is unclear. We assessed the necessity of myelin regulatory factor (Myrf) in remyelination after contusive SCI by deleting the gene from platelet-derived growth factor receptor alpha positive (PDGFRα-positive) oligodendrocyte precursor cells (OPCs) in mice prior to SCI. While OPC proliferation and density were not altered by Myrf inducible knockout after SCI, the accumulation of new oligodendrocytes was prevented. This greatly inhibited myelin regeneration resulting in a loss of myelinated axons at the lesion epicenter. However, spontaneous locomotor recovery after SCI was not altered by remyelination failure. In controls with functional MYRF, locomotor recovery preceded the onset of substantial oligodendrocyte myelin regeneration. We next assessed locomotor recovery in a severe model of SCI where fewer axons were spared. Here animals were still able to recover despite the inhibition of remyelination. We noticed that ion channels were redistributed in demyelinated axons. Further testing showed knockout animals were able to show conduction properties similar to that of control animals. Collectively, these data demonstrate that MYRF expression in PDGFRα-positive cell derived oligodendrocytes is indispensable for oligodendrocyte myelin regeneration following contusive SCI, that remyelination is not required for spontaneous recovery of stepping in moderate or severe injuries, and that demyelinated axons redistribute voltage gated ion channels and conduction properties similar to that of unmyelinated axons.

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