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Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment.

Szymanski CR, Chiha W, Morellini N, Cummins N, Bartlett CA, O'Hare Doig RL, Savigni DL, Payne SC, Harvey AR, Dunlop SA, Fitzgerald M - PLoS ONE (2013)

Bottom Line: Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation.Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes.Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site.

View Article: PubMed Central - PubMed

Affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Crawley, Western Australia, Australia.

ABSTRACT
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 stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month) administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

No MeSH data available.


Related in: MedlinePlus

Cytochromec oxidase activity after injury, +/− 670 nm light.Semi – quantification of mean ± SEM cytochrome c oxidase activity in ON including both the dorsal injury site and the ventral region vulnerable to secondary degeneration (a) or in ventral ON only (b) from normal animals and 1, 3, 7 days, 1 and 3 months after injury. Similarly, mean ± SEM cytochrome c oxidase activity in handled normal, PT handled or PT 670 nm treated animals, encompassing the dorsal injury site and ventral ON (c), or in ventral ON only, 1 day after injury (d). Mean ± SEM cytochrome c oxidase activity encompassing the dorsal injury site and ventral ON (defined by region enclosed in dotted lines in F) in PT handled or PT 670 nm treated ON compared to handled normal, 3 months after injury (e); representative images of cytochrome c oxidase activity histochemistry at 3 months (f), scale bar  = 100 μm (n = 4–5 animals/group), * significant differences indicated (p≤0.05), PT is partial ON transection injury.
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pone-0066448-g004: Cytochromec oxidase activity after injury, +/− 670 nm light.Semi – quantification of mean ± SEM cytochrome c oxidase activity in ON including both the dorsal injury site and the ventral region vulnerable to secondary degeneration (a) or in ventral ON only (b) from normal animals and 1, 3, 7 days, 1 and 3 months after injury. Similarly, mean ± SEM cytochrome c oxidase activity in handled normal, PT handled or PT 670 nm treated animals, encompassing the dorsal injury site and ventral ON (c), or in ventral ON only, 1 day after injury (d). Mean ± SEM cytochrome c oxidase activity encompassing the dorsal injury site and ventral ON (defined by region enclosed in dotted lines in F) in PT handled or PT 670 nm treated ON compared to handled normal, 3 months after injury (e); representative images of cytochrome c oxidase activity histochemistry at 3 months (f), scale bar  = 100 μm (n = 4–5 animals/group), * significant differences indicated (p≤0.05), PT is partial ON transection injury.

Mentions: Given that increased CML immunoreactivity in oligodendrocytes is associated with altered node/paranode structure (Figs. 1–3), we asked whether an antioxidant strategy would limit these myelin – related changes. Cytochrome c oxidase is a mitochondrial enzyme and a photoacceptor of light at 670 nm; treatment with 670 nm light has been shown to increase the activity of the enzyme, enhance oxidative metabolism in a range of model systems [23], [39], [40] and reduce an indicator of oxidative stress [28]. We first assessed endogenous cytochrome c oxidase activity at increasing times after injury in our model (without 670 nm treatment), using semi – quantitative assessments of histochemical staining intensity in longitudinal sections. We observed increased cytochrome c oxidase activity at 3 and 7 days after injury when assessing the ON including both the dorsal injury site and the ventral region (Fig. 4a, p≤0.001, dF  = 5), and also when assessing ventral ON only (Fig. 4b, p = 0.002, dF  = 5).


Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment.

Szymanski CR, Chiha W, Morellini N, Cummins N, Bartlett CA, O'Hare Doig RL, Savigni DL, Payne SC, Harvey AR, Dunlop SA, Fitzgerald M - PLoS ONE (2013)

Cytochromec oxidase activity after injury, +/− 670 nm light.Semi – quantification of mean ± SEM cytochrome c oxidase activity in ON including both the dorsal injury site and the ventral region vulnerable to secondary degeneration (a) or in ventral ON only (b) from normal animals and 1, 3, 7 days, 1 and 3 months after injury. Similarly, mean ± SEM cytochrome c oxidase activity in handled normal, PT handled or PT 670 nm treated animals, encompassing the dorsal injury site and ventral ON (c), or in ventral ON only, 1 day after injury (d). Mean ± SEM cytochrome c oxidase activity encompassing the dorsal injury site and ventral ON (defined by region enclosed in dotted lines in F) in PT handled or PT 670 nm treated ON compared to handled normal, 3 months after injury (e); representative images of cytochrome c oxidase activity histochemistry at 3 months (f), scale bar  = 100 μm (n = 4–5 animals/group), * significant differences indicated (p≤0.05), PT is partial ON transection injury.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3686728&req=5

pone-0066448-g004: Cytochromec oxidase activity after injury, +/− 670 nm light.Semi – quantification of mean ± SEM cytochrome c oxidase activity in ON including both the dorsal injury site and the ventral region vulnerable to secondary degeneration (a) or in ventral ON only (b) from normal animals and 1, 3, 7 days, 1 and 3 months after injury. Similarly, mean ± SEM cytochrome c oxidase activity in handled normal, PT handled or PT 670 nm treated animals, encompassing the dorsal injury site and ventral ON (c), or in ventral ON only, 1 day after injury (d). Mean ± SEM cytochrome c oxidase activity encompassing the dorsal injury site and ventral ON (defined by region enclosed in dotted lines in F) in PT handled or PT 670 nm treated ON compared to handled normal, 3 months after injury (e); representative images of cytochrome c oxidase activity histochemistry at 3 months (f), scale bar  = 100 μm (n = 4–5 animals/group), * significant differences indicated (p≤0.05), PT is partial ON transection injury.
Mentions: Given that increased CML immunoreactivity in oligodendrocytes is associated with altered node/paranode structure (Figs. 1–3), we asked whether an antioxidant strategy would limit these myelin – related changes. Cytochrome c oxidase is a mitochondrial enzyme and a photoacceptor of light at 670 nm; treatment with 670 nm light has been shown to increase the activity of the enzyme, enhance oxidative metabolism in a range of model systems [23], [39], [40] and reduce an indicator of oxidative stress [28]. We first assessed endogenous cytochrome c oxidase activity at increasing times after injury in our model (without 670 nm treatment), using semi – quantitative assessments of histochemical staining intensity in longitudinal sections. We observed increased cytochrome c oxidase activity at 3 and 7 days after injury when assessing the ON including both the dorsal injury site and the ventral region (Fig. 4a, p≤0.001, dF  = 5), and also when assessing ventral ON only (Fig. 4b, p = 0.002, dF  = 5).

Bottom Line: Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation.Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes.Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site.

View Article: PubMed Central - PubMed

Affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Crawley, Western Australia, Australia.

ABSTRACT
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 stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month) administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

No MeSH data available.


Related in: MedlinePlus