NIR Light Upregulates CCO, Stimulates Blood Flow

Broadband NIRS has potential as a noninvasive, in vivo means to study mechanisms of photobiomodulation and perform treatment evaluations of low-level laser/light therapy (LLLT).

In a placebo-controlled study, researchers at the University of Texas at Arlington used broadband NIRS to assess the cytochrome-c-oxydase (CCO) enzyme upregulation effects of photobiomodulation in human tissues in vivo, by measuring the LLLT-induced changes in CCO and hemoglobin (Hb) concentrations in human forearms in vivo.

Eleven healthy participants were administered with 1064-nm laser and placebo treatments on their right forearms. When the spectroscopic data was analyzed, researchers found that overall, LLLT significantly increased the HbO and CCO concentrations as compared with the placebo, while the Hb concentration was nearly unaltered by either placebo or laser treatment. As the dose of LLLT was increased, researchers observed a clear linear relationship between ΔCCO and ΔHbO, indicating the hemodynamic response of oxygen supply and blood volume was closely tied to the upregulation of CCO induced by photobiomodulation.

"This is the first time that effects of light stimulation have been quantified on living human tissue," said professor Hanli Liu. "The next challenge is to apply what was learned in a simpler system to the brain, where the light must pass through the scalp and the skull, as well as the brain. In the past several years, we have used the knowledge gained in the NIR field to detect, monitor and understand certain brain disorders, such as PTSD. But we have never utilized NIR light for treatment."

LLLT (red)/placebo (blue)-induced concentration changes of (a) [HbO], (b) [Hb], and (c) [CCO] in human forearms in vivo (mean ± SE, n = 11). In each subplot, the pink-shaded region indicates the period of LLLT/placebo treatment; *indicates significant differences in respective concentrations between LLLT and placebo treatment (0.01 < p < 0.05, paired t-test). **indicates significant differences in respective concentrations between LLLT and placebo treatment (p < 0.01, paired t-test).

The mechanism of photobiomodulation is proposed to rest on photon absorption by CCO, an enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. The more the activity of CCO increases, the more oxygen consumption and metabolic energy is produced via mitochondrial oxidative phosphorylation. Since CCO is an inducible enzyme, a longer-lasting metabolic effect is achieved by LLLT’s upregulating CCO concentration, which in turn enhances the capacity for cellular oxygen metabolism. Because neurons are highly dependent on oxygen metabolism, this photonics-bioenergetics mechanism results in metabolic and hemodynamic alterations that facilitate neuronal functioning.

Experimental setup: (a) photograph of the laser aperture for LLLT/placebo treatment and bb-NIRS fiber holder on a participant’s forearm, and (b) configuration of the I-shaped bb-NIRS probe holder (dark gray). The bundle holder held two optical fiber bundles with a separation of 1.5 cm. One bundle (in red) was connected to the tungsten halogen lamp and the other (in blue color) to the spectrometer. The LLLT/placebo treatments were administered on two sides of the middle section alternatively (pink circles).

The team is preparing to report and publish its findings of transcranial NIR stimulation on the human brain by quantifying production of CCO and increase of blood flow. Their findings may support a novel, noninvasive treatment with imaging ability, especially for memory.

The research was published in Scientific Reports (doi: 10.1038/srep30540).