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role in energy metabolism, cell homeostasis, and cell survival signaling. The secondary effects of photobiomodulation amplify the primary effects by upregulating the levels of cytochrome oxidase and thus creating more of the target molecule for PBM [13,16]. The energy density delivered by PBM is generally too low to cause concerns about heating and tissue destruction [17], and it appears to be safe even when applied long term [18]. As a treatment option for head and neck pain, for treatments of arthritis, and for carpal tunnel syndrome, PBM was shown to have an efficacy beyond the placebo effect, [19], which lead to the first FDA-approved low-level light therapy devices for pain relief [20]. Interest in the use of photobiomodulation for neuro-rehabilitation is growing and it has already shown potential in treating traumatic brain injury, stroke, psychiatric disorders, as well as neurodegenerative disease in general [21–23]. 1.1 Transcranial Photobiomodulation with Red to Near Infra-Red Light To make PBM work on the brain, one can benefit from the optical tissue window which allows wavelengths of light between approximately 650 nm and 1200 nm to travel through skin and skull, i.e. transcranially. The boundaries of the optical tissue window are defined by the strong absorption of hemoglobin and water. The penetration depth of wavelengths within those boundaries was measured for example by Tedford et al, who achieved a maximal penetration depth at a wavelength of 808 nm [24,25]. Wang and Li evaluated this further and confirmed 810 nm as well as 660 nm to be the best suitable wavelengths for transcranial photobiomodulation [26]. Considering an illumination of the brain at even deeper depths without having to open the skull, Bungart et al suggest the use of nanoparticles as an alternative light source for PBM [27]. These nanoparticles, termed ‘Bioluminescence Resonance Energy Transfer to Quantum Dots’ (BRET-Qdots), emit light in the NIR wavelength range when their luciferase enzyme is activated with coelenterazine-h substrate. The reported downside to a Enengl, Dungel #neverforget – PBM vs AD: A Systematic Review Page 6 of 25PDF Image | Photobiomodulation Against Alzheimer’s Disease
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