Oligodendroglia Are Particularly Vulnerable to Oxidative Damage after Neurotrauma In Vivo

Abstract

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 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 preoligodendrocytes 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-hydroxyguanosine 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 immunohistochemistry and hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration Injury to the CNS is characterized by oxidative damage in areas adjacent to the injury. However, the cellular subpopulations and structures most vulnerable to this damage remain to be elucidated. Here we use powerful NanoSIMS techniques to show increased oxidative damage in oligodendroglia and axons and to demonstrate that cells early in the oligodendroglial lineage are the most vulnerable to DNA oxidation. Further immunohistochemical and hybridization investigation reveals that mature oligodendrocytes derived after injury are more vulnerable to oxidative damage than their counterparts existing at the time of injury and have reduced myelin regulatory factor gene mRNA, yet preexisting oligodendrocytes are more likely to die.

Lycium barbarum(Wolfberry) Increases Retinal Ganglion Cell Survival and Affects both Microglia/Macrophage Polarization and Autophagy after Rat Partial Optic Nerve Transection

“…Many studies have used this model [4][5][6][7][8][9][10][11][12][13] . In these previous studies, PONT in rats was administrated from the superior side of optic nerves; however, in this study we cut the optic nerves from the temporal side and found that this operation was much easier to conduct than from the superior side due to the lack of obstruction from rectus superior and obliquus superior eye muscles ( Fig.…”

The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury

“…The secondary phase of injury involves a cascade of ischemia, inflammation, and cell death including, and of importance in this review, oligodendrocytes (Crowe, Bresnahan, Shuman, Masters, & Beattie, 1997;Hilton, Moulson, & Tetzlaff, 2017;Kwon, Tetzlaff, Grauer, Beiner, & Vaccaro, 2004;Norenberg, Smith, & Marcillo, 2004). Oligodendrocytes are susceptive to damage from reactive oxygen species, excitotoxicity, extracellular ATP, and pro-inflammatory cytokines all of which are present following SCI (Crowe et al, 1997;Giacci et al, 2018;Plemel et al, 2014). Preclinical data show that as the milieu of the spinal cord becomes less toxic (Crowe et al, 1997;Williams et al, 2014), a period of remyelination follows (Blight, 1985;Hesp, Goldstein, Miranda, Kaspar, & McTigue, 2015;Powers et al, 2012).…”

Oligodendroglia Are Particularly Vulnerable to Oxidative Damage After Neurotrauma In Vivo

“…3 However, the numbers of EdU-negative oligodendrocytes did not decrease until 28 days after injury. 3 It is a possibility that the numbers of these cells were reduced at 14 days after injury; however, this was not assessed.…”

“…The opportunity to explore using NanoSIMS allowed direct comparison between cellular subpopulations and structures in the context of secondary degeneration in vivo for the first time and provided direct evidence that OPCs and oligodendroglia are the most vulnerable, when compared with other cellular subpopulations and structures in the CNS. 3 …”