NG2 cell response in the CNP‐EGFP mouse after contusive spinal cord injury

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Abstract
NG2+ cells in the adult CNS are a heterogeneous population. The extent to which the subpopulation of NG2+ cells that function as oligodendrocyte progenitor cells (OPCs) respond to spinal cord injury (SCI) and recapitulate their normal developmental progression remains unclear. We used the CNP‐EGFP mouse, in which oligodendrocyte lineage cells express EGFP, to study NG2+ cells in the normal and injured spinal cord. In white matter of uninjured mice, bipolar EGFP+NG2+ cells and multipolar EGFPnegNG2+ cells were identified. After SCI, EGFP+NG2+ cell proliferation in residual white matter peaked at 3 days post injury (DPI) rostral to the epicenter, while EGFPnegNG2+ cell proliferation peaked at 7 DPI at the epicenter. The expression of transcription factors, Olig2, Sox10, and Sox17, and the basic electrophysiological membrane parameters and potassium current phenotype of the EGFP+NG2+ population after injury were consistent with those of proliferative OPCs during development. EGFPnegNG2+ cells did not express transcription factors involved in oligodendrogenesis. EGFP+CC1+ oligodendrocytes at 6 weeks included cells that incorporated BrdU during the peak of EGFP+NG2+ cell proliferation. EGFPnegCC1+ oligodendrocytes were never observed. Treatment with glial growth factor 2 and fibroblast growth factor 2 enhanced oligodendrogenesis and increased the number of EGFPnegNG2+ cells. Therefore, based on EGFP and transcription factor expression, spatiotemporal proliferation patterns, and response to growth factors, two populations of NG2+ cells can be identified that react to SCI. The EGFP+NG2+ cells undergo cellular and physiological changes in response to SCI that are similar to those that occur in early postnatal NG2+ cells during developmental oligodendrogenesis.