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Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo. Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-Ethynyl-2′-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 d after injury. Injury led to increases in DNA, protein, and lipid damage in oligodendrocyte progenitor cells and mature oligodendrocytes at 3 d, regardless of proliferative state, associated with a decline in the numbers of oligodendrocyte progenitor cells at 7 d. O4+ preoligoden-drocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8-hydro-xyguanosine immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced myelin regulatory factor gene mRNA, indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+; oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochem-istry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo.
|Number of pages||14|
|Journal||The Journal of neuroscience : the official journal of the Society for Neuroscience|
|Publication status||Published - 18 Jul 2018|
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Innovative and multi-disciplinary treatment strategies for secondary degeneration following neurotrauma
1/01/15 → 30/12/18
- 54 Citations
- 1 Comment/debate
Giacci, M. & Fitzgerald, M., 1 Nov 2018, In: Journal of Experimental Neuroscience. 12, p. 1-3 3 p.
Research output: Contribution to journal › Comment/debate › peer-reviewOpen Access