Effects of Photobiomodulation on Changes in Cognitive Function and Regional Cerebral Blood Flow in Patients with Mild Cognitive Impairment: A Pilot Uncontrolled Trial.

BACKGROUND: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. OBJECTIVE: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. METHODS: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. RESULTS: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. CONCLUSION: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.

Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease.

Photobiomodulation using low-level light-emitting diode can be rapidly applied in neurological and physiological disorders safely and noninvasively. Photobiomodulation is effective for chronic diseases because of fewer side effects than drugs. Here we investigated the effects of photobiomodulation using light-emitting diode on amyloid plaques, gliosis, and neuronal loss to prevent and/or recover cognitive impairment, and optimal timing of photobiomodulation initiation for recovering cognitive function in a mouse model of Alzheimer's disease. 5XFAD mice were used as an Alzheimer's disease model. Animals receiving photobiomodulation treatment were divided into two groups: an early group starting photobiomodulation at 2 months of age (5XFAD+Early), and a late group starting photobiomodulation at 6 months of age (5XFAD+Delay). Both groups received photobiomodulation 20 minutes per session three times per week for 14 weeks. The Morris water maze, passive avoidance, and elevated plus maze tests were performed at 10 months of age. Immunohistochemistry and Western blot were performed after behavioral evaluation. The results showed that photobiomodulation treatment at early stages reduced amyloid accumulation, neuronal loss, and microgliosis and alleviated the cognitive dysfunction in 5XFAD mice, possibly by increasing insulin degrading enzyme related to amyloid-beta degradation. Photobiomodulation may be an excellent candidate for advanced preclinical Alzheimer's disease research.

Smartphone-Driven Low-Power Light-Emitting Device.

Low-level light (laser) therapy (LLLT) has been widely researched in the recent past. Existing LLLT studies were performed based on laser. Recently, studies using LED have increased. This study presents a smartphone-driven low-power light-emitting device for use in colour therapy as an alternative medicine. The device consists of a control unit and a colour probe. The device is powered by and communicates with a smartphone using USB On-The-Go (OTG) technology. The control unit controls emitting time and intensity of illumination with the configuration value of a smartphone application. Intensity is controlled by pulse width modulation (PWM) without feedback. A calibration is performed to resolve a drawback of no feedback. To calibrate, intensity is measured in every 10 percent PWM output. PWM value is linearly calibrated to obtain accurate intensity. The device can control the intensity of illumination, and so, it can find application in varied scenarios.

Low-level light emitting diode therapy promotes long-term functional recovery after experimental stroke in mice.

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU+ ) in the ischemic brain, and significant increases in BrdU+ /GFAP+ , BrdU+ /DCX+ , BrdU+ /NeuN+ , and CD31+ cells in the subacute LED-T group. However, the BrdU+ /Iba-1+ cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.

Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms.

Photostimulation with low-level light emitting diode therapy (LED-T) modulates neurological and psychological functions. The purpose of this study was to evaluate the effects of LED-T pretreatment on the mouse brain after ischemia/reperfusion and to investigate the underlying mechanisms. Ischemia/reperfusion brain injury was induced by middle cerebral artery occlusion. The mice received LED-T twice a day for 2 days prior to cerebral ischemia. After reperfusion, the LED-T group showed significantly smaller infarct and edema volumes, fewer behavioral deficits compared to injured mice that did not receive LED-T and significantly higher cerebral blood flow compared to the vehicle group. We observed lower levels of endothelial nitric oxide synthase (eNOS) phosphorylation in the injured mouse brains, but significantly higher eNOS phosphorylation in LED-T-pretreated mice. The enhanced phospho-eNOS was inhibited by LY294002, indicating that the effects of LED-T on the ischemic brain could be attributed to the upregulation of eNOS phosphorylation through the phosphoinositide 3-kinase (PI3K)/Akt pathway. Moreover, no reductions in infarct or edema volume were observed in LED-T-pretreated eNOS-deficient (eNOS-/-) mice. Collectively, we found that pretreatment with LED-T reduced the amount of ischemia-induced brain damage. Importantly, we revealed that these effects were mediated by the stimulation of eNOS phosphorylation via the PI3K/Akt pathway.

Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1ß and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression.

Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice.

PURPOSE: Transcranial low-level light therapy (LLLT) has gained interest as a non-invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. METHODS: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. RESULTS: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF-κB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. CONCLUSIONS: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption.

Randomized controlled trial of the efficacy and safety of self-adhesive low-level light therapy in women with primary dysmenorrhea.

OBJECTIVE: To evaluate the efficacy and safety of low-level light therapy in women with primary dysmenorrhea. METHOD: A multicenter prospective, randomized, double-blind, placebo-controlled clinical trial including patients 18-35 years of age with primary dysmenorrhea was undertaken at two university hospitals in South Korea between October 2011 and September 2012. Patients were randomized using a computer-generated sequence to receive low-level light therapy using the Color DNA-WSF device or to receive placebo treatment with a dummy device. The severity of menstrual pain, assessed using a visual analog scale, was the primary outcome and was evaluated at baseline and during every menstrual cycle for 3 months following treatment. Patients who received more than one application of treatment (with a Color DNA-WSF or placebo device) were included in analyses. Patients and investigators were masked to the treatment assignments. RESULTS: Overall, 44 patients were assigned to each group. At the final study visit, the reduction in scores using a visual analog scale was significantly greater in patients who received low-level light therapy (n=41; 4.34±2.22) than among those in the control group (n=38; 1.79±1.73; P<0.001 when adjusted for age) No serious adverse events occurred. CONCLUSION: Low-level light therapy could be an effective, safe treatment modality for women with primary dysmenorrhea. Clinical Trials.gov: NCT02026206.

Skin adhesive low-level light therapy for dysmenorrhoea: a randomized, double-blind, placebo-controlled, pilot trial.

PURPOSE: The cause of dysmenorrhoea is an abnormal function of smooth muscles in the uterus due to long-term deficient blood supply into smooth muscle tissue. The purpose of this study was to evaluate the effectiveness of skin adhesive low-level light therapy (LLLT) in participants with dysmenorrhoea. METHODS: Thirty-one women were included in this randomized, double-blind, placebo-controlled, pilot trial. Twenty-one women were treated with active LLLT and ten women were treated with placebo one. The therapy was performed in a laboratory room for 20 min a day over a period of 5 days prior to the expected onset of menstruation. The outcome was measured using a visual analog scale (VAS) for each participant's dysmenorrhoeal pain severity. VAS of each subject was measured every month for 6 months. RESULTS: In the active LLLT group, 16 women reported successful results during their first menstrual cycle just after active LLLT and 5 women had successful results from the second menstrual cycle after active LLLT. The pain reduction rate was 83 % in the active LLLT group, whereas there was only a slight and temporary reduction in pain in the placebo LLLT group. Changes of VAS within 6 months of LLLT showed statistical significance (p = 0.001) over placebo control. CONCLUSIONS: Our study suggests that skin adhesive LLLT on acupuncture points might be an effective, simple and safe non-pharmacological treatment for dysmenorrhoea.