Oligodendroglia Are Particularly Vulnerable to Oxidative Damage After Neurotrauma In Vivo

Abstract

In the paper “Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo,” we determined the extent of oxidative damage to specific cellular subpopulations and structures within regions vulnerable to secondary degeneration and assessed the effect this had on oligodendroglial function. Comparative assessment of oxidative damage demonstrated selective vulnerability of oligodendroglia, specifically oligodendrocyte progenitor cells (OPCs) to DNA oxidation in vivo. Immunohistochemical fate mapping along the oligodendroglial lineage showed a transient susceptibility of these cells to DNA oxidation, protein nitration, and lipid peroxidation, with mature oligodendrocytes derived immediately after injury more vulnerable to DNA oxidation than their counterparts existing at the time of injury or later derived. In situ hybridization demonstrated a reduction in myelin regulatory factor (MyRF) messenger RNA (mRNA) fluorescence in newly derived mature oligodendrocytes, suggesting a compromise in the production and maintenance of the myelin sheath in these cells. The data imply a deficit in the normal differentiation of OPCs to myelinating oligodendrocytes, associated with a transient increase in oxidative damage, which may contribute to the dysmyelinating phenotype seen at chronic time points after injury. Identifying and understanding the sources of this oxidative damage is integral for the development of therapeutic interventions for neurotrauma.

Iron Metabolism in Oligodendrocytes and Astrocytes, Implications for Myelination and Remyelination

“…The malfunction of these antioxidant mechanisms due to high intracellular iron concentrations might induce mitochondrial injury and energy deficiency in astrocytes and microglial cells, which can further amplify ROS production. In addition, levels of antioxidant molecules are relatively low in mature myelinating oligodendrocytes (Giacci et al, 2018). Thus, both mechanisms may further contribute to the vulnerability of these cells to oxidative stress in inflammatory demyelinating diseases.…”

Pre-clinical and Clinical Implications of “Inside-Out” vs. “Outside-In” Paradigms in Multiple Sclerosis Etiopathogenesis

“…Nevertheless, the progression of white matter injury is poorly understood in TBI. Oligodendrocytes are known to be vulnerable to oxidative stress and excitotoxicity following traumatic injury (Lotocki et al, 2011;Giacci and Fitzgerald, 2018). The loss of oligodendrocytes could significantly contribute to underlying demyelination after injury (Dent et al, 2015;Armstrong et al, 2016b) and activate neuroinflammation (Mierzwa et al, 2015).…”

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, ; Hilton, Moulson, & Tetzlaff, ; Kwon, Tetzlaff, Grauer, Beiner, & Vaccaro, ; Norenberg, Smith, & Marcillo, ). 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, ; Giacci et al, ; Plemel et al, ). Preclinical data show that as the milieu of the spinal cord becomes less toxic (Crowe et al, ; Williams et al, ), a period of remyelination follows (Blight, ; Hesp, Goldstein, Miranda, Kaspar, & McTigue, ; Powers et al, ).…”