Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin oxygenation induced by near-infrared laser

Photobiomodulation, also known as low-level laser/light therapy (LLLT), refers to the use of red-to-near-infrared light to stimulate cellular functions for physiological or clinical benefits. The mechanism of LLLT is assumed to rely on photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. In this study, we used broadband near-infrared spectroscopy (NIRS) to measure the LLLT-induced changes in CCO and hemoglobin concentrations in human forearms in vivo. Eleven healthy participants were administered with 1064-nm laser and placebo treatments on their right forearms. The spectroscopic data were analyzed and fitted with wavelength-dependent, modified Beer-Lambert Law. We found that LLLT induced significant increases of CCO concentration (Δ[CCO]) and oxygenated hemoglobin concentration (Δ[HbO]) on the treated site as the laser energy dose accumulated over time. A strong linear interplay between Δ[CCO] and Δ[HbO] was observed for the first time during LLLT, indicating a hemodynamic response of oxygen supply and blood volume closely coupled to the up-regulation of CCO induced by photobiomodulation. These results demonstrate the tremendous potential of broadband NIRS as a non-invasive, in vivo means to study mechanisms of photobiomodulation and perform treatment evaluations of LLLT.

[1]  Marco Ferrari,et al.  Near Infrared Brain and Muscle Oximetry: From the Discovery to Current Applications , 2012 .

[2]  E. Gratton,et al.  Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy. , 1999, Physics in medicine and biology.

[3]  A. Villringer,et al.  Cross talk in the Lambert-Beer calculation for near-infrared wavelengths estimated by Monte Carlo simulations. , 2002, Journal of biomedical optics.

[4]  Britton Chance,et al.  Photobiomodulation Directly Benefits Primary Neurons Functionally Inactivated by Toxins , 2005, Journal of Biological Chemistry.

[5]  Douglas W. Barrett,et al.  Augmentation of cognitive brain functions with transcranial lasers , 2014, Front. Syst. Neurosci..

[6]  A. Yodh,et al.  Diffuse optics for tissue monitoring and tomography , 2010, Reports on progress in physics. Physical Society.

[7]  Booncharoen Sirinaovakul,et al.  Introduction to the Special Issue , 2002, Comput. Intell..

[8]  F. Gonzalez-Lima,et al.  Protection against neurodegeneration with low-dose methylene blue and near-infrared light , 2015, Front. Cell. Neurosci..

[9]  M. Greco,et al.  Specific helium-neon laser sensitivity of the purified cytochrome c oxidase , 2000, International journal of radiation biology.

[10]  F. Gonzalez-Lima,et al.  Cognitive enhancement by transcranial laser stimulation and acute aerobic exercise , 2016, Lasers in Medical Science.

[11]  Marc Fisher,et al.  Infrared Laser Therapy for Ischemic Stroke: A New Treatment Strategy: Results of the NeuroThera Effectiveness and Safety Trial–1 (NEST-1) , 2007, Stroke.

[12]  Nicola J. Robertson,et al.  Brain mitochondrial oxidative metabolism during and after cerebral hypoxia–ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy , 2014, NeuroImage.

[13]  F. Gonzalez-Lima,et al.  Mitochondrial respiration as a target for neuroprotection and cognitive enhancement. , 2014, Biochemical pharmacology.

[14]  D Piao,et al.  Trans-rectal ultrasound-coupled spectral optical tomography of total hemoglobin concentration enhances assessment of the laterality and progression of a transmissible venereal tumor in canine prostate. , 2011, Urology.

[15]  C. Ahn,et al.  Two case reports , 2017, Medicine.

[16]  Gemma Bale,et al.  A new broadband near-infrared spectroscopy system for in-vivo measurements of cerebral cytochrome-c-oxidase changes in neonatal brain injury. , 2014, Biomedical optics express.

[17]  B. Tromberg,et al.  Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy , 2011, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[18]  Anita Saltmarche,et al.  Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. , 2011, Photomedicine and laser surgery.

[19]  Martin Smith,et al.  Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin☆ , 2014, NeuroImage.

[20]  T. Karu,et al.  Absorption measurements of a cell monolayer relevant to phototherapy: reduction of cytochrome c oxidase under near IR radiation. , 2005, Journal of photochemistry and photobiology. B, Biology.

[21]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[22]  A. Eke,et al.  The modified Beer–Lambert law revisited , 2006, Physics in medicine and biology.

[23]  W. Todd Maddox,et al.  Improving executive function using transcranial infrared laser stimulation , 2017, Journal of neuropsychology.

[24]  Michele Henry,et al.  Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. , 2004, Mitochondrion.

[25]  R. Gagnon,et al.  Comparison of 13 published cytochrome c oxidase near-infrared spectroscopy algorithms , 2006, European Journal of Applied Physiology and Occupational Physiology.

[26]  Michael T. Manry,et al.  A Preliminary Investigation of Human Frontal Cortex Under Noxious Thermal Stimulation Over the Temporomandibular Joint Using Functional Near Infrared Spectroscopy , 2013 .

[27]  J. Kingsley,et al.  Low-level laser therapy as a treatment for chronic pain , 2014, Front. Physiol..

[28]  Douglas W. Barrett,et al.  Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans , 2013, Neuroscience.

[29]  Brian W Pogue,et al.  Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide , 2013, Journal of biomedical optics.

[30]  P. H. Koh,et al.  Functional optical topography analysis using Statistical Parametric Mapping (SPM) methodology with and without physiological confounds , 2010, Advances in experimental medicine and biology.

[31]  Marc Fisher,et al.  Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke , 2009, Stroke.

[32]  David A. Boas,et al.  Twenty years of functional near-infrared spectroscopy: introduction for the special issue , 2014, NeuroImage.

[33]  Hanli Liu,et al.  Transcranial laser stimulation improves human cerebral oxygenation , 2016, Lasers in surgery and medicine.

[34]  Christopher G. Beevers,et al.  Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults with Elevated Depression Symptoms , 2016, Brain Stimulation.

[35]  Hellmuth Obrig,et al.  Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact , 2004, NeuroImage.

[36]  F Gonzalez-Lima,et al.  Neurological and psychological applications of transcranial lasers and LEDs. , 2013, Biochemical pharmacology.

[37]  Ilias Tachtsidis,et al.  Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults , 2012, Biomedical optics express.

[38]  Ross Zafonte,et al.  Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study. , 2014, Journal of neurotrauma.

[39]  S. Jacques Optical properties of biological tissues: a review , 2013, Physics in medicine and biology.

[40]  F. Gonzalez-Lima,et al.  Low-level light therapy improves cortical metabolic capacity and memory retention. , 2012, Journal of Alzheimer's disease : JAD.

[41]  D. Delpy,et al.  Performance comparison of several published tissue near-infrared spectroscopy algorithms. , 1995, Analytical biochemistry.

[42]  M. Ferrari,et al.  A brief review on the use of functional near-infrared spectroscopy (fNIRS) for language imaging studies in human newborns and adults , 2012, Brain and Language.

[43]  Daqing Piao,et al.  Trans-rectal ultrasound-coupled near-infrared optical tomography of the prostate, part II: experimental demonstration. , 2008, Optics express.

[44]  Mark I. Johnson,et al.  Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials , 2009, The Lancet.

[45]  Ilias Tachtsidis,et al.  A Hybrid Multi-Distance Phase and Broadband Spatially Resolved Spectrometer and Algorithm for Resolving Absolute Concentrations of Chromophores in the Near-Infrared Light Spectrum , 2010, Advances in experimental medicine and biology.

[46]  Martin Wolf,et al.  A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology , 2014, NeuroImage.

[47]  Michael R Hamblin,et al.  Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety , 2009, Behavioral and Brain Functions.