Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation

Abstract

Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neuro-degeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8±3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6±2.9 %. MTT reduction rate was reduced to 75.9±2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6±4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9±4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6±13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.

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

“…Nonetheless, the precise mechanisms by which tissues benefit from NIR therapy has not been fully characterized. Previous studies reported that NIR could provide neurologic benefit through activation of COX by stimulating controlled release of ROS and subsequent recruitment of antioxidant defenses 54 , or promote ATP synthesis, providing relief from energy depletion during ischemia 55 . NIR was also reported to activate angiogenesis 56 , to increase COX levels 57 , and to modulate protein synthesis 58 and activity 46 .…”

Near infrared light decreases synaptic vulnerability to amyloid beta oligomers

“…In these experiments, we focused on synaptic mitochondria function as one possible mechanism contributing to the observed synaptic resilience to Aβ oligomers induced by NIR light exposure. Previous studies have described the mitochondria as a key element targeted by NIR light treatment 10 , 11 , 27 , 28 and reported that preserving synaptic mitochondria efficiency protects synapses from Aβ oligomers 20 , 28 . We first analyzed by flow cytometry synaptosomes from wild type and Tg2576 mice treated or not with NIR light that had been labeled with MitoTracker, a mitochondrion-specific fluorescent dye whose stain intensity is directly proportional to the number of mitochondria 29 .…”

“…With this goal in mind, in the present work we investigated the effect of a treatment with near infrared light (NIR, 600 to 1000 nm wavelength) in increasing synaptic resilience to Aβ oligomers. NIR light treatment administered in a noninvasive transcranial application has been suggested to photostimulate the mitochondrial chromophore, cytochrome c oxidase, resulting in increased ATP formation 8 – 11 . Mitochondrial dysfunction is a pathological event occurring in early stages of AD.…”

Direct 1O2 optical excitation: A tool for redox biology

“…In contrast, Yu et al have found a protective role of 810 nm light in an oxygen-glucose deprivation neuronal model in vitro [153], [154]. However the light fluence employed (3 J cm −2 ) with a cw diode 810 nm laser is between 3 and 23 times smaller than that employed by Fonseca et al .…”