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 (ΔΨm), 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.

Raman Spectroscopy Follows Time-Dependent Changes in T Lymphocytes Isolated from Spleen of Endotoxemic Mice

“…These observed morphological changes in the spleen have been reported as a result of LPS insult (64), and it is also known that cleaved caspase-3-positive cells significantly increase in numbers after the LPS exposure causing widespread leukocyte apoptosis in the spleen tissue (65). The tissue injury hypothesis can be further confirmed with the presence of Raman vibrations arising from the cytochrome-c/heme moiety and is in accordance with reported studies in literature where presence of cytochrome and heme during tissue injury in organs such as brain has been observed (38,66,67). The k-means clustering image captures to some extent the contributions of DNA and heme.…”

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

“…In comparison to former studies on RL/NIRL, our results demonstrate the participation of additional complexes I and II besides the proposed photoacceptor CCO [12,21,24,25,28,44]. Our results indicate that CCO may not be the main target of PBM action, leading to reduced oxidative stress.…”

Stress-mediated generation of deleterious ROS in healthy individuals - role of cytochrome c oxidase

“…The physiological significance of the "allosteric ATP inhibition of COX" was recently verified by experiments of Hüttemann and coworkers, who discovered inhibition of COX activity by near-infrared light of 750-and 950-nm wavelength. The near-infrared light reduced the mitochondrial membrane potential (ΔΨ m ), attenuated mitochondrial superoxide production (ROS), and in turn neuronal death of cultured HT22 cells following glutamate exposure and oxygenglucose deprivation [93]. In living animals of a rat stroke model with a longitudinal analysis of brain injury using magnetic resonance imaging, a sustained reduction in infarct volume following ischemic stroke was found after exposure to near-infrared light [94].…”