Dataset Information

Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

ABSTRACT: The interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX-inhibitory wavelengths reduced mitochondrial respiration, reduced the mitochondrial membrane potential (ΔΨ_m), attenuated mitochondrial superoxide production, and attenuated neuronal death following oxygen glucose deprivation, whereas NIR that activates COX provided no benefit. We evaluated COX-inhibitory NIR as a potential therapy for cerebral reperfusion injury using a rat model of global brain ischemia. Untreated animals demonstrated an 86% loss of neurons in the CA1 hippocampus post-reperfusion whereas inhibitory NIR groups were robustly protected, with neuronal loss ranging from 11% to 35%. Moreover, neurologic function, assessed by radial arm maze performance, was preserved at control levels in rats treated with a combination of both COX-inhibitory NIR wavelengths. Taken together, our data suggest that COX-inhibitory NIR may be a viable non-pharmacologic and noninvasive therapy for the treatment of cerebral reperfusion injury.

SUBMITTER: Sanderson TH

PROVIDER: S-EPMC5823933 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

Sanderson Thomas H TH Wider Joseph M JM Lee Icksoo I Reynolds Christian A CA Liu Jenney J Lepore Bradley B Tousignant Reneé R Bukowski Melissa J MJ Johnston Hollie H Fite Alemu A Raghunayakula Sarita S Kamholz John J Grossman Lawrence I LI Przyklenk Karin K Hüttemann Maik M

Scientific reports 20180222 1

The interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX-inhibitory wavelengths reduced mitoch ...[more]

PMID: 29472564

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Project description:ContextNear infrared spectroscopy (NIRS) is a noninvasive tool for assessing local oxygen balance. In circulatory shock, the microcirculatory environment as measured by NIRS during resuscitation may provide additional diagnostic tools of value to the critical care physician.HypothesisTo assess whether a relative increase in peripheral NIRS was correlated with a clinically relevant increase in cardiac output following a fluid bolus in a swine model of shock.Methods and modelsNine healthy young adult swine with median weight 80 kg (interquartile range, 75-83 kg) were anesthetized and surgically instrumented. They underwent a controlled hemorrhage of 20% of their blood volume followed by partial or complete aortic occlusion to create a variable ischemia-reperfusion injury. Next, the animals underwent four 500-mL plasmalyte boluses over 9 minutes each followed by a 6-minute pause. The animal then underwent a 25% mixed auto/homologous blood transfusion followed by four more 500 mL plasmalyte boluses over 9 minutes. Finally, the animals underwent a 25% mixed auto/homologous blood transfusion followed by an additional four rounds of 500-mL plasmalyte boluses over 9 minutes. Left thoracic limb NIRS, descending thoracic aortic flow (dAF), arterial blood pressure (MAP), central venous pressure (CVP), and mixed central venous oxygen saturation (Svo2) were measured continuously for comparison.ResultsThe area under the receiver operating curve for an increase in dAF of 10% in response to a 500 mL bolus based on a percent increase in the proximal NIRS was 0.82 with 95% CI, 0.72-0.91; Svo2, 0.86 with 95% CI, 0.78-0.95; MAP, 0.75 with 95% CI, 0.65-0.85 and CVP, 0.64 with 95% CI, 0.53-0.76.Interpretation and conclusionsA dynamic relative increase in NIRS in response to a crystalloid challenge has moderate discriminatory power for cardiac output augmentation during shock in a swine model of ischemia-reperfusion injury. NIRS performed as well as invasive measurements (Svo2 and MAP) and better than CVP.

Project description:Transcranial near-infrared stimulation (tNIRS) has been proposed as a tool to modulate cortical excitability. However, the underlying mechanisms are not clear where the heating effects on the brain tissue needs investigation due to increased near-infrared (NIR) absorption by water and fat. Moreover, the risk of localized heating of tissues (including the skin) during optical stimulation of the brain tissue is a concern. The challenge in estimating localized tissue heating is due to the light interaction with the tissues' constituents, which is dependent on the combination ratio of the scattering and absorption properties of the constituent. Here, apart from tissue heating that can modulate the cortical excitability ("photothermal effects"); the other mechanism reported in the literature is the stimulation of the mitochondria in the cells which are active in the adenosine triphosphate (ATP) synthesis. In the mitochondrial respiratory chain, Complex IV, also known as the cytochrome c oxidase (CCO), is the unit four with three copper atoms. The absorption peaks of CCO are in the visible (420-450 nm and 600-700 nm) and the near-infrared (760-980 nm) spectral regions, which have been shown to be promising for low-level light therapy (LLLT), also known as "photobiomodulation". While much higher CCO absorption peaks in the visible spectrum can be used for the photobiomodulation of the skin, 810 nm has been proposed for the non-invasive brain stimulation (using tNIRS) due to the optical window in the NIR spectral region. In this article, we applied a computational approach to delineate the "photothermal effects" from the "photobiomodulation", i.e., to estimate the amount of light absorbed individually by each chromophore in the brain tissue (with constant scattering) and the related tissue heating. Photon migration simulations were performed for motor cortex tNIRS based on a prior work that used a 500 mW cm - 2 light source placed on the scalp. We simulated photon migration at 630 nm and 700 nm (red spectral region) and 810 nm (near-infrared spectral region). We found a temperature increase in the scalp below 0.25 °C and a minimal temperature increase in the gray matter less than 0.04 °C at 810 nm. Similar heating was found for 630 nm and 700 nm used for LLLT, so photothermal effects are postulated to be unlikely in the brain tissue.

Dataset Information

Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

Publications

Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury.

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