Section I

Photobiomodulation

Photobiomodulation therapy is defined as the utilization of non-ionizing photonic energy to trigger photochemical changes within cellular structures that are receptive to photons. Mitochondria is particularly receptive to this process. At the cellular level, visible red and near infrared light (NIR) energy are absorbed by mitochondria, which perform the function of producing cellular energy called “ATP”. The key to this entire process is a mitochondrial enzyme called cytochrome oxidase c, a chromophore, which accepts photonic energy of specific wavelengths when functioning below par.

Photobiology

Photobiology is the study of the effects of non-ionizing radiation on biological systems. The biological effect varies with the wavelength region of the radiation. The radiation is absorbed by molecules in skin such as DNA, protein or certain drugs. The molecules are changed chemically into products that initiate biochemical responses in the cells.

Biological reaction to light is nothing new, there are numerous examples of light induced photochemical reactions in biological systems. Vitamin D synthesis in our skin is an example of a photochemical reaction. The power density of sunlight is only 105 mW/cm2 yet when ultraviolet B (UVB) rays strikes our skin, it converts a universally present form of cholesterol, 7-dehydrocholesterol to vitamin D3. We normally experience this through our eyes which are obviously photosensitive. Our vision is based upon light hitting our retinas and creating a chemical reaction that allows us to see. Throughout the course of evolution, photons have played a vital role in photo-chemically energizing certain cells. 

Pathways

  • NO (Nitric Oxide)
  • ROS (Reactive Oxygen Series) → PKD (gene) → IkB (Inhibitor κB) + NF-κB (nuclear factor κB) → NF-κB (nuclear factor κB stimulates gene transcription)
  • ATP (Adenosine Triphosphate) → cAMP (catabolite activator protein) → Jun/Fos (oncogenic transcription factors) → AP-1 (activator protein transcription factor stimulates gene transcription)

Mechanism

The current  and widely accepted proposal is that the low level visible red to near infrared light (NIR) energy is absorbed by mitochondria and converted into ATP for cellular use. In addition, the process creates mild oxidants (ROS), which leads to gene transcription and then to cellular repair and healing. The process also unclogs the chain that has been clogged by nitric oxide (NO).[1] The nitric oxide is then released back into the system. Nitric oxide is a molecule that our body produces to help its 50 trillion cells communicate with each other. This communication happens by transmission of signals throughout the entire body. Additionally, nitric oxide helps to dilate the blood vessels and improve blood circulation.

Photobiomodulation mechanisms

Section II

Parameters

The correct wavelength for the target cells or chromophores must be employed (633-810 nm). However, if the wavelength is incorrect, optimum absorption will not occur. Thus, as the first law of photobiology, the Grotthus-Draper law, states — without absorption there can be no reaction.[2]

The photon intensity, i.e., spectral irradiance or power density (W/cm2), must be adequate, or absorption of the photons will not be sufficient to attain the desired result. However, if the intensity is too high, the photon energy will be transformed to excessive heat in the target tissue, and that is undesirable.[3]

Finally, the dose or fluence must also be adequate (J/cm2). Consequently, if the power density is too low, then prolonging the irradiation time to achieve the ideal energy density, or dose, will, most likely, not give an adequate final result. This happens because the Bunsen-Roscoe law of reciprocity, the 2nd law of photobiology, does not hold true for low incident power densities.[4]

Section III

Brain Bioenergetics

Near-infrared light (NIR) stimulates mitochondrial respiration in neurons by donating photons that are absorbed by cytochrome oxidase. This is a bioenergetics process called photoneuromodulation in nervous tissue.[5]The absorption of luminous energy by the enzyme results in increased brain cytochrome oxidase enzymatic activity and oxygen consumption. Since the enzymatic reaction catalyzed by cytochrome oxidase is the reduction of oxygen to water, acceleration of cytochrome oxidase catalytic activity directly causes an increase in cellular oxygen consumption.[6] Increased oxygen consumption by nerve cells is coupled to oxidative phosphorylation. Hence, ATP production increases as a consequence of the metabolic action of near-infrared light. This type of luminous energy can enter brain mitochondria transcranially, and — independently of the electrons derived from food substrates — it can directly photostimulate cytochrome oxidase activity.[7]

Section IV

References

[1] – “Biphasic Dose Response in Low Level Light Therapy”; Sulbha K. Sharma (PhD), Ying-Ying Huang (MD), James Carroll, Michael R. Hamblin (PhD)

[2, 3, 4] – “Is light-emitting diode phototherapy (LED-LLLT) really effective?”; Won-Serk Kim (PhD, MD), R Glen Calderhead (PhD)

[5, 6, 7] – “Augmentation of cognitive brain functions with transcranial infrared light”; Francisco Gonzalez-Lima (PhD), Douglas W Barrett (MD)

Brain Photobiomodulation

Mechanisms of Brain Photobiomodulation

“Low-energy photon irradiation in the near-IR spectral range with low-energy lasers or LEDs positively modulates various important biological processes in cell culture and animal models. Photobiomodulation is applied clinically in the treatment of soft tissue injuries and accelerated wound healing. The mechanism of photobiomodulation by red to near-IR light at the cellular level has been ascribed by research institutions to the activation of cellular mitochondrial respiratory chain components, resulting in a signaling cascade that promotes cellular proliferation and cytoprotection.

Research indicates that cytochrome c oxidase is a key photo-acceptor of irradiation in the far-red to near-IR spectral range. Cytochrome c oxidase is an integral membrane protein that contains multiple redox active metal centers. Additionally, it has a strong absorbency in the far-red to near-IR spectral range detectable in-vivo by near-IR spectroscopy.

Additionally, photobiomodulation increases the rate of electron transfer in purified cytochrome oxidase, increasing mitochondrial respiration and ATP synthesis in isolated mitochondria, and up-regulating cytochrome oxidase activity in cultured neuronal cells – leading to neuroprotective effects and neuronal function.

In addition to increased oxidative metabolism, red to near-IR light stimulation of mitochondrial electron transfer is known to increase the generation of reactive oxygen species (ROS). ROS functions as signaling molecules, providing communication between mitochondria and the nucleus.”[1]

[1] – Proc Natl Acad Sci U S A. 2003 Mar 18; 100(6): 3439–3444.

Brain Bioenergetics

neuron photobiomodulation

It is important to note that neurons contain mitochondria.

The process of utilizing the science of photobiomodulation to energize neuronal mitochondria triggers a cascade of beneficial cellular events.

Some potential effects are : neuroprotective effects, self-repair mechanisms and enhanced function.[1]

[1] : “Neurological and psychological applications of transcranial LEDs“, Department of Psychology and Institute for Neuroscience, University of Texas

Photonic Diffusion

photobiomodulation brain
brain photobiomodulation

A Pitzschke, B Lovisa, O Seydoux, M Zellweger, M Pfleiderer, Y Tardy and G Wagnières (2015). Red and NIR light dosimetry in the human deep brain., Federal Institute of Technology (EPFL), Institute of Chemical Sciences and Engineering (ISIC), 1015 Lausanne, Switzerland, Phys. Med. Biol. 60 (2015) 2921–2937

Electromagnetic radiation within the NIR range carries the most potent form of photonic diffusion through tissue, blood and brain.

In the entire electromagnetic spectrum, the 810 nm wavelength exhibits the least photonic scattering. Furthermore, it presents good absorption by blood and water.

Clinical studies have shown that NIR light of sufficient power density is capable of diffusing transcranially. Thus, the light can penetrate through the scalp, skull and brain to depths of 4 cm or more.  Furthermore, the NIR light can also diffuse intranasally, through the nasal channel.