Cells of the oligodendrocyte lineage proliferate following cortical stab wounds: An in vitro analysis
✍ Scribed by José A. Amat; Muhammad Farooq; Hideaki Ishiguro; William T. Norton
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 109 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
We have previously shown that a cortical stab wound induces the proliferation of microglia and astrocytes in situ, but no evidence was obtained for proliferation of cells of the oligodendrocyte lineage . To study further the properties of cells involved in repair following brain injury, groups of adult rats received either sham operations or bilateral stab wounds. Proliferating cells were labeled in vivo 3 days later with [ 3 H]-thymidine (Thy) and sacrificed the same day. Oligodendrocyte-enriched preparations were isolated, cultured, and analyzed. The fate and antigenic phenotype of the proliferating cells was analyzed using three-color immunofluorescence combined with autoradiography at 1, 2, 3, 5, and 10 days in vitro (DIV). Cells were immunostained for ganglioside GD3 (glial stem cells), O4 antigen (cells of the oligodendrocyte lineage), galactosyl ceramide (GC, differentiated oligodendrocytes), and GFAP (astrocytes). Thymidine-labeled O4ϩ/GCϪ cells were found only in cultures from wounded animals and most of them differentiated in vitro as mature oligodendrocytes, but no Thyϩ/O4ϩ/GCϩ oligodendrocytes were seen at 1, 2, or 3 DIV. There was also a marked increase in the number of Thyϩ/GD3ϩ cells in the experimental cultures. In both experimental and control groups the total number of Thyϩ and ThyϪ GD3ϩ cells declined with time in culture concomitant with an increase in total number of both Thyϩ and ThyϪ GFAPϩ astrocytes, and without any significant change in the Thyϩ cell fraction of O4ϩ oligodendrocytes in the experimental cultures. Therefore most of the GD3ϩ/O4Ϫ cells apparently differentiated as GFAPϩ astrocytes, not as oligodendrocytes. We conclude that O4ϩ/GCϪ oligodendrocyte precursor cells, but not differentiated oligodendrocytes, proliferate in response to brain injury. These cells proliferate slowly or not at all in normal adult animals and constitute a phenotypically and kinetically distinct group from the GD3ϩ glial precursors. This result is consistent with the existence within the adult CNS of a quiescent premyelinating oligodendrocyte. We propose that these immature committed oligodendrocytes are induced to proliferate at the wound site and serve as a source of new oligodendrocytes.