Reactive species and oxidative stress in optic nerve vulnerable to secondary degeneration
MetadataShow full item record
Secondary degeneration contributes substantially to structural and functional deficits following traumatic injury to the CNS. While it has been proposed that oxidative stress is a feature of secondary degeneration, contributing reactive species and resultant oxidized products have not been clearly identified in vivo. The study is designed to identify contributors to, and consequences of, oxidative stress in a white matter tract vulnerable to secondary degeneration. Partial dorsal transection of the optic nerve (ON) was used to model secondary degeneration in ventral nerve unaffected by the primary injury. Reactive species were assessed using fluorescent labelling and liquid chromatography/tandem mass spectroscopy (LC/MS/MS). Antioxidant enzymes and oxidized products were semi-quantified immunohistochemically. Mitophagy was assessed by electron microscopy. Fluorescent indicators of reactive oxygen and/or nitrogen species increased at 1, 3 and 7 days after injury, in ventral ON. LC/MS/MS confirmed increases in reactive species linked to infiltrating microglia/macrophages in dorsal ON. Similarly, immunoreactivity for glutathione peroxidase and haem oxygenase-1 increased in ventral ON at 3 and 7 days after injury, respectively. Despite increased antioxidant immunoreactivity, DNA oxidation was evident from 1 day, lipid oxidation at 3 days, and protein nitration at 7 days after injury. Nitrosative and oxidative damage was particularly evident in CC1-positive oligodendrocytes, at times after injury at which structural abnormalities of the Node of Ranvier/paranode complex have been reported. The incidence of mitochondrial autophagic profiles was also significantly increased from 3 days. Despite modest increases in antioxidant enzymes, increased reactive species are accompanied by oxidative and nitrosative damage to DNA, lipid and protein, associated with increasing abnormal mitochondria, which together may contribute to the deficits of secondary degeneration.
Showing items related by title, author, creator and subject.
Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light TreatmentSzymanski, C.R.; Chiha, W.; Morellini, N.; Cummins, N.; Bartlett, C.A.; Doig, R.L.O.; Savigni, D.L.; Payne, S.C.; Harvey, A.R.; Dunlop, S.A.; Fitzgerald, Melinda (2013)Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative ...
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 ...
Giacci, M.; Bartlett, Carole; Smith, N.; Iyer, K.; Toomey, Lillian; Jiang, H.; Guagliardo, P.; Kilburn, M.; Fitzgerald, Melinda (2018)Loss of function following injury to the central nervous system is worsened by secondary degeneration of neurons and glia surrounding the injury and initiated by oxidative damage. However, it is not yet known which cellular ...