Scientific Impacts of Red Light/NIR Therapy (Photobiomodulation)

Mechanisms

https://pmc.ncbi.nlm.nih.gov/articles/PMC4550182

The clinical benefit and effects of infrared phototherapy on mitochondrial function and secondary molecular events are discussed in the context of adequate radiant energy penetration.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11171912/#sec6-cells-13-00966

Neural tissue is notably abundant in mitochondria, and is thus highly responsive to light interactions, particularly with CCO, a key player in neuronal energy metabolism.

Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue – PubMed (nih.gov)

830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area.

Significant Improvements in Cognitive Performance Post-Transcranial, Red/Near-Infrared Light-Emitting Diode Treatments in Chronic, Mild Traumatic Brain Injury: Open-Protocol Study – PMC (nih.gov)

Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism.

Effect of Low-Level Laser Stimulation on EEG – PMC (nih.gov)

[remote/on the palm] Low-level laser stimulation was able to increase the power of alpha rhythms and theta waves, mainly in the posterior head regions. These effects lasted at least 15 minutes after cessation of the laser stimulation. The amplitude power of beta activities in the anterior head regions decreased after laser stimulation. We thought these EEG changes comparable to those in meditation.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5066697

LLLT may improve the healing of skin flaps by enhancing the amount of new vessels formed in the tissue. Both 660 nm and 780 nm lasers were able to modulate VEGF secretion, MMP-2 activity and HIF-1α expression in a dose dependent manner [in rats].

Anti-Inflammatory Effects

Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats – PubMed (nih.gov)

LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs [progressive retinal ganglion cell] and visual cortex.

Low level laser irradiation stimulates mitochondrial membrane potential and disperses subnuclear promyelocytic leukemia protein – PubMed (nih.gov)

…causes a shift of the cell from a quiescent to an activated stage in the cell cycle heralding proliferation and suppression of inflammation [in vitro].

Effects of 810-nm Laser on Murine Bone-Marrow-Derived Dendritic Cells – PMC (nih.gov)

810-nm LLLT has an anti-inflammatory effect on activated DC [dendritic cells], possibly mediated by cyclic adenosine monophosphate (cAMP) and reduced NF-κB signaling.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3488572

LLLT significantly reduced LPS-activated microglia-induced neuronal cell death. In LPS-activated microglia-like BV-2 cells, LLLT attenuated inflammation cytokine TNF-α, decreased the production of NO, down-regulated overexpression of iNOS, and caused MyD88 degradation.

Brain Health

https://pmc.ncbi.nlm.nih.gov/articles/PMC2587428

Twice a day of LED treatment is most effective in rescuing neurons from the toxic effects of potassium cyanide, MPP+, and rotenone.

https://pubmed.ncbi.nlm.nih.gov/16464535

Light-emitting diode pretreatment partially protects neurons against cyanide-induced caspase-mediated apoptosis, most likely by decreasing reactive oxygen species production, down-regulating pro-apoptotic proteins and activating anti-apoptotic proteins, as well as increasing energy metabolism in neurons.

Photobiomodulation (660 nm) therapy reduces oxidative stress and induces BDNF expression in the hippocampus – PMC (nih.gov)

Photobiomodulation (660 nm) therapy reduces oxidative stress and induces BDNF expression in the hippocampus [in vitro].

Cognitive Function

https://pubmed.ncbi.nlm.nih.gov/23200785

Reaction time in a sustained-attention psychomotor vigilance task (PVT) was significantly improved in the treated.

Low-level light therapy improves cortical metabolic capacity and memory retention – PubMed (nih.gov)

LLLT-treated rats had an enhanced extinction memory as compared to controls. Experiment 3 showed that LLLT reduced fear renewal and prevented the reemergence of extinguished conditioned fear responses.

Cerebral Blood Flow (CBF)/Cerebral Oxygenation

Targeted increase in cerebral blood flow by transcranial near-infrared laser irradiation – PubMed (nih.gov)

We showed that NIR laser irradiation (1.6 W/cm(2) for 15-45 minutes) increased local CBF by 30% compared to that in control mice. NIR laser irradiation also induced a significant increase in cerebral NO concentration.

The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women – PubMed (nih.gov)

TCLT [transcranial LED therapy] promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women.

Transcranial laser stimulation improves human cerebral oxygenation – PMC (nih.gov)

Transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration and a decrease of deoxygenated hemoglobin concentration in both cerebral hemispheres.

Low-level light therapy improves cortical metabolic capacity and memory retention – PubMed (nih.gov)

…LLLT induced hormetic dose-response effects on the metabolic capacity of the prefrontal cortex [in rats].

PTSD/Traumatic Brain Injury (TBI)

https://pmc.ncbi.nlm.nih.gov/articles/PMC4043367

Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4550182

Symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability improved…

https://pmc.ncbi.nlm.nih.gov/articles/PMC4640344

LLLT [Low-level laser therapy] decreased ROS, increased ATP production, reduced lesion size, and reduced time to escape [in mice].

https://pmc.ncbi.nlm.nih.gov/articles/PMC5025344

3-day LLLT treatment improved neuromuscular performance and cognitive function at 4 weeks, and this improvement continued up to 8 weeks. It induces neurogenesis in the SVZ and the DG, together with increases in BDNF expression (both at 1 week) and increases synaptogesis in the perilesional cortex at week 4 [in rats].

https://pmc.ncbi.nlm.nih.gov/articles/PMC4189010

tLLLT [transcranial LLLT] may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis [in mice].

https://pubmed.ncbi.nlm.nih.gov/28001756

Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4043367

Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions.

Stroke

https://pubmed.ncbi.nlm.nih.gov/17463313

Infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset.

https://pubmed.ncbi.nlm.nih.gov/27180104

The combination of TLT-tPA enhances ATP production, and suggests that tPA-induced reperfusion in combination with TLT neuroprotection therapy may optimally protect viable cells in the cortex.

Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5′-triphosphate (ATP) content following embolic strokes in rabbits – PubMed (nih.gov)

That represented a 41% and 77% increase in ATP content compared to naive control rabbits.

Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits – PubMed (nih.gov)

A noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.

Treatment of experimentally induced transient cerebral ischemia with low energy laser inhibits nitric oxide synthase activity and up-regulates the expression of transforming growth factor-beta 1 – PubMed (nih.gov)

Low energy laser could suppress the activity of NOS and up-regulate the expression of TGF-beta1 after stroke in rats.

Pretreatment with light-emitting diode therapy reduces ischemic brain injury in mice through endothelial nitric oxide synthase-dependent mechanisms – PubMed (nih.gov)

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.

Depression/Anxiety

https://pmc.ncbi.nlm.nih.gov/articles/PMC2796659

Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks.

https://pmc.ncbi.nlm.nih.gov/articles/PMC4556873

Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5215986

LLLT of 808nm exerts efficacious depressive attenuation on depression-like behaviors by decreasing the immobility and promoting motor activity [in mice].

Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety – PMC (nih.gov)

Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks.

https://pubmed.ncbi.nlm.nih.gov/23200785

Overall affect improved significantly in the treated group due to more sustained positive emotional states.

Alzheimer’s & Parkinson’s Disease

https://pubmed.ncbi.nlm.nih.gov/24387311

NIr may have potential as an effective, minimally-invasive intervention for mitigating, and even reversing, progressive cerebral degenerations.

https://pubmed.ncbi.nlm.nih.gov/24857852

Treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the ‘abscopal effect’ sometimes observed in radiation treatment of metastatic cancer [in mice].

https://pmc.ncbi.nlm.nih.gov/articles/PMC6705158

LLLT rescued neurons loss and dendritic atrophy via upregulation of BDNF in both Aβ-treated hippocampal neurons and cultured APP/PS1 mouse hippocampal neurons [in vitro].

https://www.scirp.org/journal/paperinformation?paperid=56921

Transcatheter treatment allows reducing the effects of dyscirculatory angiopathy of Alzheimer’s type (DAAT) improving cerebral microcirculation and metabolism, which leads to permanent dementia regression and cognitive impairment reduction.

https://pmc.ncbi.nlm.nih.gov/articles/PMC3706077

LED pretreatment for only 80 seconds per day for only two days significantly rescued more striatal and cortical neurons from apoptotic cell death induced by either rotenone or MPP+. LED pretreatment also substantially increase cellular content of ATP in primary neurons grown in rotenone or MPP+ [in vitro].

https://pmc.ncbi.nlm.nih.gov/articles/PMC2587428

LED treatment increased cytochrome oxidase activity and ATP production and reduced the generation of apoptosis, reactive oxygen species, and reactive nitrogen species in poisoned neurons…These findings pave the way for future testing of LED treatment for Parkinson’s diseased animal models or patients.

https://pmc.ncbi.nlm.nih.gov/articles/PMC5458630

Molecular studies revealed that LLI treatment: (1) restored mitochondrial dynamics, by altering fission and fusion protein levels thereby suppressing Aβ-induced extensive fragmentation; (2) suppressed Aβ-induced collapse of mitochondrial membrane potential; (3) reduced oxidized mitochondrial DNA and excessive mitophagy; (4) facilitated mitochondrial homeostasis via modulation of the Bcl-2-associated X protein/B-cell lymphoma 2 ratio and of mitochondrial anti-oxidant expression; (5) promoted cytochrome c oxidase activity and adenosine triphosphate synthesis; (6) suppressed Aβ-induced glucose-6-phosphate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activity; (7) enhanced the total antioxidant capacity of hippocampal CA1 neurons, whereas reduced the oxidative damage; and (8) suppressed Aβ-induced reactive gliosis, inflammation, and tau hyperphosphorylation [in rats].

Photobiomodulation by low-power laser irradiation attenuates Aβ-induced cell apoptosis through the Akt/GSK3β/β-catenin pathway

LPLI [low-power laser irradiation] has a prosurvival effect on Aβ-induced apoptosis and may be an effective therapeutic strategy in treating AD by targeting GSK3β.

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