Response of NG2-expressing cells to spinal cord contusion: Evidence for the stimulation of oligodendrocyte progenitor cells (OPCs) and non-OPC populations

Abstract

Contusive spinal cord injury results in both immediate and secondary injury. Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and are especially susceptible to secondary injury. Oligodendrocyte cell death results in abnormal myelination, disrupting action potential propagation. Recently, a pool of heterogeneous Nerve/Glial antigen 2-expressing (NG2⁺) cells, including NG2⁺ oligodendrocyte progenitor cells (OPCs), has been described in the adult CNS. These cells are quiescent in the naïve spinal cord, but are capable of responding to injury. Studies in the rat indicate that NG2⁺ cell proliferation peaks within the first week following contusion, and that cells proliferating acutely become mature glia chronically. I was interested in understanding the progression and physiological response of these progenitor cells in the acute injury phase in a murine model of contusive injury, as mouse models offer powerful advantages through both natural genetic aberrations and genetically induced alterations. An initial in vitro study of dissociated NG2⁺ cells from the acutely injured adult, naïve adult, and naive early postnatal rat spinal cords revealed that the injured NG2⁺ cell population has physiological and antigenical differences than both naïve populations. Furthermore, NG2⁺ cells that were not of the oligodendrocyte lineage were a significant portion of NG2⁺ cells isolated from the adult, but not the early postnatal rat, supporting recent research suggesting that not all NG2⁺ cells are OPCs, and that these cells arise later in development. These initial studies prompted studies in vivo, using the C57Bl/6 mouse and the CNP-EGFP (2-3-cyclic nucleotide 3-phosphodiesterase-enhanced green fluorescent protein) transgenic mouse which allows for visualization of oligodendrocyte lineage cells, including NG2⁺ OPCs. I observed EGFP ⁺ NG2⁺ OPCs as well as potentially other NG2 ⁺ cell types. Both EGFP⁺ NG2⁺ OPCs and EGFP^- NG2⁺ cells proliferate in the first week following injury, and both populations are present in the chronically injured animal. Antigenic characterization and electrophysiological analysis of the EGFP⁺ NG2⁺ cells indicates that adult OPCs retain programs associated with OPCs during development, and that some events after injury recapitulate development. Further examination of non-EGFP NG2 ⁺ cell populations reveals possible roles for these cells as astrocyte precursor cells, other stem/progenitor cells, and/or a non-progenitor NG2 ⁺ cell population that may be involved in homeostatic functions.