Myelinogenic Plasticity of Oligodendrocyte Precursor Cells and Role of Remyelination in Locomotor RecoveryFollowing Contusive Spinal Cord Injury

Spontaneous remyelination occurs after spinal cord injury(SCI), but the extent of myelin repair and identity of the cellsresponsible remain incompletely understood and contentious.We assessed the cellular origin of new myelin by fate mappingplatelet-derived growth factor receptor α (PDGFRα), Olig۲+,and P۰+ cells following contusion SCI in mice. Oligodendrocyteprecursor cells (OPCs; PDGFRα+) produced oligodendrocytesresponsible for de novo ensheathment of at least ۳۰%of myelinated spinal axons at injury epicenter ۳ months afterSCI, demonstrating that these resident cells are a major contributorto oligodendrocyte regeneration. OPCs also producedthe majority of myelinating Schwann cells in the injured spinalcord; invasion of peripheral myelinating (P۰+) Schwanncells made only a limited contribution. These findings revealthat PDGFRα+ cells perform diverse roles in CNS repair, asmultipotential progenitors that generate both classes of myelinatingcells.We subsequently assessed the necessity of myelin regulatoryfactor (Myrf) in remyelination after contusive SCI by deletingthe gene from platelet-derived growth factor receptor alphapositive (PDGFRα-positive) oligodendrocyte progenitor cells(OPCs) in mice prior to SCI. While OPC proliferation and densitywere not altered by Myrf inducible knockout after SCI, theaccumulation of new oligodendrocytes was largely prevented.This greatly inhibited myelin regeneration resulting in a ۴۴%reduction in myelinated axons at the lesion epicenter. However,spontaneous locomotor recovery after SCI was not altered byremyelination failure. In controls with functional MYRF, locomotorrecovery preceded the onset of substantial oligodendrocytemyelin regeneration. Collectively, these data demonstratethat MYRF expression in PDGFRα-positive cell derived oligodendrocytesis indispensable for oligodendrocyte myelin regenerationfollowing contusive SCI but that remyelination is notrequired for spontaneous recovery of overground locomotionand stepping.