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Rojas and Gonzalez-Lima Dovepress Table 3 Beneficial in vivo transcranial effects of low-level light therapy on the brain Source Laser Laser Laser Laser Laser Laser LED Laser Laser LED Wavelength 808 nm 808 nm 808 nm 808 nm 808 nm 808 nm 633 and 870 nm LED cluster 670 nm 1072 nm 810 nm Dose 1.6 w/cm2, 4320 J/cm2 7.5 mw/cm2, 0.9 J/cm2, 2 minutes per point 25 mw/cm2, 15,000 J/cm2, continuous 25 mw/cm2, 15,000 J/cm2, pulsed at 1 KHz 1 J/cm2 per point 10 or 20 mw/cm2, 1.2–2.4 J/cm2, single point for 2 minutes 22.2 mw/cm2, 13.3 J/cm2, 10 minutes per placement 40 mw/cm2, 2 J/cm2 in four fractions 6 minutes × 10 days 250 mw/cm2, 60 J/cm2 Effect Increased cerebral blood flow and decreased hippocampal and cortical neuronal death after unilateral BCCAO (mouse) improved neurological recovery, increased subventricular neural proliferation after MCAO (rat) improved motor function and reduction in effective clot dose for stroke 3 hours after clot injection (rabbit) increased cortical ATP, decreased effective clot dose for stroke 6 hours after clot injection (rabbit) improved clinical outcome at 90 days after ischemic stroke (human) improved motor behavior 5 days after closed-head injury, and decreased brain lesion size from 12.1% to 1.4% at 28 days after injury (mouse) improved cognition of two patients with chronic mild traumatic brain injury after 2–4 months of treatment (human) Reduction in substantia nigra dopaminergic cell loss after MPTP toxicity (mouse) improved acquisition of working memory for spatial navigation in middle-aged mice (mouse) Decreased depression scores, increased prefrontal blood flow (human) Relevance Anoxic brain injury Atherothrombotic stroke Embolic stroke Embolic stroke ischemic stroke Traumatic brain injury (acute) Traumatic brain injury (chronic) Parkinson’s disease Mild cognitive impairment, Alzheimer’s disease Depression, prefrontal functions Reference Uozumi et al,86 DeTaboada et al,88 Oron et al,89 Lapchak et al,90 Lapchak et al91–93 Lampl et al,94 Oron et al,96 Naeser et al,97 Shaw et al,99 Michalikova et al,104 Schiffer et al,84 Abbreviations: ATP, adenosine triphosphate; BCCAO, bilateral common carotid artery occlusion; LED, light-emitting device; MCAO, middle cerebral artery occlusion; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. the memory performance of LLLT-treated middle-aged mice became comparable to that of young mice. These data sup- port that LLLT could be particularly useful at facilitating acquisition of a working memory task in conditions in which information processing speed is impaired, such as aging. Experimental data in humans also support that LLLT may be effective in the treatment of cognitive and emotional disorders in humans. A pilot study showed that LLLT applied transcranially to the forehead was able to increase frontal cortex blood flow and induce a 63% reduction in depression scores in a group of patients with major depression. Beneficial antidepressant effects were seen 2 weeks and 4 weeks after a single treatment. LLLT was given in one fraction at 810 nm, power density of 250 mW/cm2.84 Additionally, LLLT to the forehead and scalp with an LED cluster at 633 nm and 870 nm has been reported to improve and maintain atten- tion, executive function, and memory in two patients with chronic traumatic brain injury.97 LLLT with a power density of 22.2 mW/cm2 was applied for 10 minutes per placement weekly for 2 months or daily for 4 months prior to testing of the cognitive effects, and these patients have continued daily treatment at home for up to 5.5 years. Remarkably, no side effects have been reported so far with the use of LLLT in humans (Table 3). Research on the application of LLLT for the improvement of brain function is expected to increase in the following years. The use of this technology will benefit from further studies looking for optimal LLLT parameters and treatment protocols. Current preclinical data support the feasibility of formal randomized placebo-controlled trials, and these will likely be developed in the near future. Conclusion LLLT or photobiomodulation refers to the use of low-power and high-fluence light from lasers or LEDs in the red to near-infrared wavelengths to modulate a biological function. Cytochrome oxidase is the primary photoacceptor of LLLT with beneficial eye and brain effects since this mitochon- drial enzyme is crucial for oxidative energy metabolism, and neurons depend on cytochrome oxidase to produce their metabolic energy. Photon-induced redox mechanisms in cytochrome oxidase cause other primary and secondary Eye and Brain 2011:3 64 submit your manuscript | www.dovepress.com DovepressPDF Image | Low-level light therapy of the eye and brain
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