Early Proliferation Does Not Prevent the Loss of Oligodendrocyte Progenitor Cells during the Chronic Phase of Secondary Degeneration in a CNS White Matter Tract
MetadataShow full item record
Partial injury to the central nervous system (CNS) is exacerbated by additional loss of neurons and glia via toxic events known as secondary degeneration. Using partial transection of the rat optic nerve (ON) as a model, we have previously shown that myelin decompaction persists during secondary degeneration. Failure to repair myelin abnormalities during secondary degeneration may be attributed to insufficient OPC proliferation and/or differentiation to compensate for loss of oligodendrocyte lineage cells (oligodendroglia). Following partial ON transection, we found that sub-populations of oligodendroglia and other olig2+ glia were differentially influenced by injury. A high proportion of NG2+/olig2–, NG2+/olig2+ and CC1−/olig2+ cells proliferated (Ki67+) at 3 days, prior to the onset of death (TUNEL+) at 7 days, suggesting injury-related cues triggered proliferation rather than early loss of oligodendroglia. Despite this, a high proportion (20%) of the NG2+/olig2+ OPCs were TUNEL+ at 3 months, and numbers remained chronically lower, indicating that proliferation of these cells was insufficient to maintain population numbers. There was significant death of NG2+/olig2– and NG2−/olig2+ cells at 7 days, however population densities remained stable, suggesting proliferation was sufficient to sustain cell numbers. Relatively few TUNEL+/CC1+ cells were detected at 7 days, and no change in density indicated that mature CC1+ oligodendrocytes were resistant to secondary degeneration in vivo. Mature CC1+/olig2– oligodendrocyte density increased at 3 days, reflecting early oligogenesis, while the appearance of shortened myelin internodes at 3 months suggested remyelination. Taken together, chronic OPC decreases may contribute to the persistent myelin abnormalities and functional loss seen in ON during secondary degeneration.
Showing items related by title, author, creator and subject.
Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration following neurotraumaSavigni, D.; O'Hare Doig, R.; Szymanski, C.; Bartlett, C.; Lozic, I.; Smith, N.; Fitzgerald, Melinda (2013)Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca 2+ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca ...
Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotraumaO'Hare Doig, R.; Chiha, W.; Giacci, M.; Yates, N.; Bartlett, C.; Smith, N.; Hodgetts, S.; Harvey, A.; Fitzgerald, Melinda (2017)Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux ...
Changes to mitochondrial ultrastructure in optic nerve vulnerable to secondary degeneration in vivo are limited by irradiation at 670 nmCummins, N.; Bartlett, C.; Archer, M.; Bartlett, E.; Hemmi, J.; Harvey, A.; Dunlop, S.; Fitzgerald, Melinda (2013)Background: Traumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration. Key events thought to be associated with secondary degeneration involve ...