Photobiomodulation and Coenzyme Q 10 Treatments Attenuate Cognitive Impairment Associated With Model of Transient Global Brain Ischemia in Artificially Aged Mice
Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10) administration are known to stimulate mitochondrial electron transport that potentially may reverse the effects of cerebral ischemia in aged animals. We tested the hypothesis that the effects of PBM and CoQ10, separately or in combination, improve cognition in a mouse model of transient cerebral ischemia superimposed on a model of aging. We modeled aging by 6-week administration of D-galactose (500 mg/kg subcutaneous) to mice. We subsequently induced transient cerebral ischemia by bilateral occlusion of the common carotid artery (BCCAO). We treated the mice with PBM (810 nm transcranial laser) or CoQ10 (500 mg/kg by gavage), or both, for 2 weeks after surgery. We assessed cognitive function by the Barnes and Lashley III mazes and the What-Where-Which (WWWhich) task. PBM or CoQ10, and both, improved spatial and episodic memory in the mice. Separately and together, the treatments lowered reactive oxygen species and raised ATP and general mitochondrial activity as well as biomarkers of mitochondrial biogenesis, including SIRT1, PGC-1α, NRF1, and TFAM. Neuroinflammatory responsiveness declined, as indicated by decreased iNOS, TNF-α, and IL-1β levels with the PBM and CoQ10 treatments. Collectively, the findings of this preclinical study imply that the procognitive effects of NIR PBM and CoQ10 treatments, separately or in combination, are beneficial in a model of transient global brain ischemia superimposed on a model of aging in mice.
Coenzyme Q10; aging; global ischemia; learning and memory; mitochondrial biogenesis; neuroinflammation; transcranial photobiomodulation.
Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury
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.
Conflict of interest
statementT.H.S. and M.H. are co-founders of Mitovation Inc. that develops infrared light therapy for ischemia/reperfusion injury applications. All other authors declare that they have no conflicts of interest with the contents of this article.
A new treatment protocol using photobiomodulation and muscle/bone/joint recovery techniques having a dramatic effect on a stroke patient’s recovery: a new weapon for clinicians
The subject of this case study is a 29-year-old woman who suffered a brainstem stroke. She remained severely dizzy, had a non-functional left hand secondary to weakness, severe spasticity in the right hand, a right lateral sixth nerve palsy and was unable to ambulate on presentation. The stroke occurred 2 years before presentation. The subject had been treated for 21 months at two different stroke rehabilitation centres before presentation. Our stroke protocol includes photobiomodulation administered with the XR3T-1 device and ‘muscle/bone/joint/soft tissue’ recovery techniques. The patient was seen once a week for 8 weeks and treatment sessions lasted approximately 60 min. The results were dramatic: after 8 weeks of implementation of our protocol, the patient demonstrated positive change in every area of her deficits as determined by improvements in physical examination findings. The gains achieved at 8 weeks have been maintained to this day and she continues to be treated once every 4 weeks.