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Differential effects of 670 and 830 nm red near infrared irradiation therapy: a comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury.

Giacci MK, Wheeler L, Lovett S, Dishington E, Majda B, Bartlett CA, Thornton E, Harford-Wright E, Leonard A, Vink R, Harvey AR, Provis J, Dunlop SA, Hart NS, Hodgetts S, Natoli R, Van Den Heuvel C, Fitzgerald M - PLoS ONE (2014)

Bottom Line: Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model.Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05).Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05).

View Article: PubMed Central - PubMed

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

ABSTRACT
Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

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Number of Tunel+ cells, 8OHDG and GFAP immunoreactivity following pre-treatment with 670 nm or 830 nm R/NIR-IT or sham treatment and light induced retinal degeneration, compared to uninjured animals.Mean ± SEM total number of Tunel+ cells/retinal section (A) and number of Tunel+ cells in superior and inferior retina (B) were quantified. Mean ± SEM 8OHDG and GFAP immunoreactivities in retinal sections were semi-quantified (C): *indicates significantly different from injured control (P≤0.05), n = 6/group. Representative images of 8OHDG (green) and GFAP (red) immunofluorescence from control and R/NIR-IT treated animals are shown (D) (scale  = 200 µm).
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pone-0104565-g003: Number of Tunel+ cells, 8OHDG and GFAP immunoreactivity following pre-treatment with 670 nm or 830 nm R/NIR-IT or sham treatment and light induced retinal degeneration, compared to uninjured animals.Mean ± SEM total number of Tunel+ cells/retinal section (A) and number of Tunel+ cells in superior and inferior retina (B) were quantified. Mean ± SEM 8OHDG and GFAP immunoreactivities in retinal sections were semi-quantified (C): *indicates significantly different from injured control (P≤0.05), n = 6/group. Representative images of 8OHDG (green) and GFAP (red) immunofluorescence from control and R/NIR-IT treated animals are shown (D) (scale  = 200 µm).

Mentions: Light damage induces cell death, indicated by large numbers of TUNEL positive (+) cells in rat retina from as early as 6 hours after injury, particularly in the photoreceptor layers, as described previously [60], [61]. We detected no effect of pre-treatment with 830 nm R/NIR-IT on numbers of TUNEL+ cells relative to controls (F = 1.417, dF = 5, P>0.05) (Fig 3A). In contrast, we observed a significant decrease in the total number of TUNEL+ photoreceptors in the outer nuclear layer of LD retinae pre-treated with 670 nm R/NIR-IT compared with controls, confirming previous findings (F = 1.678, dF = 5, P≤0.05) [62], [63]. The lower numbers of TUNEL+ cells in retinas treated with 670 nm R/NIR-IT were significant in samples taken from both superior retina and inferior retina (F = 3.423, dF = 2, P≤0.05) (Fig. 3B). Immunoreactivity for 8OHDG, indicative of oxidised DNA and therefore oxidative stress, was significantly reduced in LD retinae treated with 670 nm R/NIR-IT (F = 1.632, dF = 4, P≤0.05), but not those treated with 830 nm R/NIR-IT (F = 3.267, dF = 4, P>0.05) (Fig. 3C). While there was a trend towards reduced GFAP immunoreactivity following treatment of light damaged retinae with 670 nm R/NIR-IT, this was not significant (F = 1.867 dF = 4, P>0.05) (Figs. 3C, D).


Differential effects of 670 and 830 nm red near infrared irradiation therapy: a comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury.

Giacci MK, Wheeler L, Lovett S, Dishington E, Majda B, Bartlett CA, Thornton E, Harford-Wright E, Leonard A, Vink R, Harvey AR, Provis J, Dunlop SA, Hart NS, Hodgetts S, Natoli R, Van Den Heuvel C, Fitzgerald M - PLoS ONE (2014)

Number of Tunel+ cells, 8OHDG and GFAP immunoreactivity following pre-treatment with 670 nm or 830 nm R/NIR-IT or sham treatment and light induced retinal degeneration, compared to uninjured animals.Mean ± SEM total number of Tunel+ cells/retinal section (A) and number of Tunel+ cells in superior and inferior retina (B) were quantified. Mean ± SEM 8OHDG and GFAP immunoreactivities in retinal sections were semi-quantified (C): *indicates significantly different from injured control (P≤0.05), n = 6/group. Representative images of 8OHDG (green) and GFAP (red) immunofluorescence from control and R/NIR-IT treated animals are shown (D) (scale  = 200 µm).
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Related In: Results  -  Collection

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pone-0104565-g003: Number of Tunel+ cells, 8OHDG and GFAP immunoreactivity following pre-treatment with 670 nm or 830 nm R/NIR-IT or sham treatment and light induced retinal degeneration, compared to uninjured animals.Mean ± SEM total number of Tunel+ cells/retinal section (A) and number of Tunel+ cells in superior and inferior retina (B) were quantified. Mean ± SEM 8OHDG and GFAP immunoreactivities in retinal sections were semi-quantified (C): *indicates significantly different from injured control (P≤0.05), n = 6/group. Representative images of 8OHDG (green) and GFAP (red) immunofluorescence from control and R/NIR-IT treated animals are shown (D) (scale  = 200 µm).
Mentions: Light damage induces cell death, indicated by large numbers of TUNEL positive (+) cells in rat retina from as early as 6 hours after injury, particularly in the photoreceptor layers, as described previously [60], [61]. We detected no effect of pre-treatment with 830 nm R/NIR-IT on numbers of TUNEL+ cells relative to controls (F = 1.417, dF = 5, P>0.05) (Fig 3A). In contrast, we observed a significant decrease in the total number of TUNEL+ photoreceptors in the outer nuclear layer of LD retinae pre-treated with 670 nm R/NIR-IT compared with controls, confirming previous findings (F = 1.678, dF = 5, P≤0.05) [62], [63]. The lower numbers of TUNEL+ cells in retinas treated with 670 nm R/NIR-IT were significant in samples taken from both superior retina and inferior retina (F = 3.423, dF = 2, P≤0.05) (Fig. 3B). Immunoreactivity for 8OHDG, indicative of oxidised DNA and therefore oxidative stress, was significantly reduced in LD retinae treated with 670 nm R/NIR-IT (F = 1.632, dF = 4, P≤0.05), but not those treated with 830 nm R/NIR-IT (F = 3.267, dF = 4, P>0.05) (Fig. 3C). While there was a trend towards reduced GFAP immunoreactivity following treatment of light damaged retinae with 670 nm R/NIR-IT, this was not significant (F = 1.867 dF = 4, P>0.05) (Figs. 3C, D).

Bottom Line: Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model.Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05).Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05).

View Article: PubMed Central - PubMed

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

ABSTRACT
Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P ≤ 0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P ≤ 0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P ≤ 0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.

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Related in: MedlinePlus