How does RLT help?
There appears to be neuroprotective effects of laser and light-emitting diodes (LED) in diverse neurological conditions, such as traumatic brain injury (TBI), ischemic stroke, Alzheimer’s disease, Parkinson’s disease, as well as age-related cognitive decline. Besides these therapeutic effects at the molecular level, there is also considerable evidence of changes occurring at the behavioral level such as cognitive enhancement, antidepressant effects, and improved sleep.
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The brain, along with the heart and muscle, are the tissues with the greatest mitochondrial density. Mitochondria, which are extremely important for our health, longevity and energy production, respond exceptionally well to red/NIR light. Thus, the brain and overall cognitive function (i.e. Alzheimer's disease) has a great capacity to heal with RLT.
It is believed that impaired cerebral vascular perfusion is the one of the first manifestations of most brain disorders. RLT can increase the neuronal nitric oxide content, increase the vessel diameter, and improve cerebral blood flow (CBF). Therefore, it could be considered that RLT of specific areas of the brain potentially affects regional CBF.
Mitochondrial dysfunction is another root cause underlying the vast majority of brain diseases. In Alzheimer’s disease (AD), mitochondrial dysfunction is the primary source of reactive oxygen species (ROS) and contributes to the oxidative damage and neuroinflammation that induces neuronal damage and apoptosis. Mitochondrial dysfunction contributes to the development of depression and anxiety by impairing neurogenesis, neuronal transmission, and synaptic plasticity necessary for successful adaptation to stressful conditions. Therefore, approaches targeting mitochondrial dysfunction may represent a potential avenue for preventing depression, anxiety and memory loss in the development of AD.
Neuroinflammation is one of the crucial pathophysiological findings in brain disorders, which is chiefly mediated by activated microglial cells (microglial cells remove damaged neurons and infections and are important for maintaining the health of the CNS). RLT reduces pro-inflammatory cytokines via inhibition of various signaling pathways, resulting in attenuation of inflammatory reactions. Evidence supports the idea that the anti-inflammatory effects of brain RLT may at least partly be due to its ability to modulate microglial activity and a subsequent decrease in inflammatory mediators.
Recent clinical brain RLT studies have been focused on conditions such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), traumatic brain injury and ischemic stroke.
AD: significant improvements in sleep quality, mood states, EEG patterns, as well as improved cognitive function including memory & attention have been obtained as a consequence of NIR RLT
PD: In the only study in PD patients, improved motor and cognitive functions has been reported following 2 weeks of trans-cranial RLT. Other RLT-positive effects include: decreased Aβ production, Increase Aβ degradation and clearance, increased BDNF, decreased p-tau, decreased inflammation, increased memory, increased mitochondrial function and protection and increased energy. Gut health seems to be another important aspect of PD (read section below on PD and gut health).
Stroke: an effort has been made in occasional studies to show neuroprotective or neuroreparative effects of RLT in chronic stroke patients via transcranial and multiple area irradiation methods.
While the cause of autism spectrum disorder (ASD) is uncertain, the most widely accepted explanation is that it is a complex neurodevelopmental disorder characterized by brain network abnormalities. EEG has shown local overconnectivity and long-range underconnectivity, also involving the corpus callosum. fMRI studies revealed altered functional connectivity in the default mode network, a network with a role in interoceptive awareness and mind wandering and which was implicated in social-cognitive deficits of autism.
The main goal of therapy for children with ASD is the improvement of socio-relational and communication skills. This goal is pursued through a combination of interventions, such as speech therapy, parent training, social skills training and cognitive-behavioral therapy. In the presence of emotional and behavioral dysregulation, a pharmacological approach is often considered.
Recently, there has been a growing interest in the potential of non-invasive brain stimulation in neurodevelopmental disorders, thanks to their ability to modulate neuroplasticity and enhance cognitive, behavioral and socio-emotional processes.
Among new neuromodulation approaches, is transcranial photobiomodulation (tPBM), which is RLT through the skull. The target for light within single neurons is the mitochondria, where tPBM stimulates cytochrome c oxidase. The consequence is that light enhances mitochondrial activity and hence ATP synthesis, leading to an activation of transcription factors associated with increased functional activity.
Along with adults, tPBM could also be safely and efficiently used in children and adolescents, considering that several studies used RLT to treat pediatric samples with no reported or minimal side effects. In fact, research conducted in 2018 achieved results that demonstrated decreased irritability after treatment, suggesting the potential of tPBM also in treatment of children with ASD.
Across the world, the number of people aged 60 and over has been growing faster than any other age group. The increase in life expectancy is related to many factors, including changes in the quality of life of the population, greater urbanization, nutritional improvement, increased personal hygiene, better sanitary conditions and adequate work and home environments. On the other hand, longevity has been accompanied by an increase in cases of neurological diseases associated with aging, such as late-onset Alzheimer’s disease (AD) and PD among others. However, aging is a physiological process not yet fully understood.
Aging is a multifactorial biological process, characterized by a decline in physiological functions, including brain functions that leads to diminished cognitive health. Studies with animals and humans demonstrate that RLT can improve cognitive function during this phase of life. It is likely that the capacity of RLT to facilitate brain energy and hemodynamic metabolism, reduce inflammatory and oxidative stress levels and regulate the rate of apoptotic proteins is closely related to the beneficial effects on cognitive functions. Moreover, there is no evidence in the literature that RLT adversely affects brain activity in healthy older adults and patients with brain damage. Thus, we can consider RLT to be a promising strategy for treating the cognitive deficits observed during aging.
Transcranial photobiomodulation (tPBM) is one of the main ways to treat the brain via NIR light. tPBM can help improve cognitive health by increasing oxygenation, improving regional circulation and nutritional supplementation to the brain parenchyma by triggering nitric oxide production, which is an effective vasodilator. tPBM exerts anti-inflammatory function through modulation of NF-κB system, tumor necrosis factor (TNFα) and beneficial regulation of other pro- and anti-inflammatory cytokines in brain parenchyma. Through complex regulation of signaling molecules and certain transcription factors, tPBM light activates anti-apoptotic, and anti-senescence cascades, and further exerts neuroprotective effects on both healthy and impaired brain cells and tissue. tPBM can also promote synaptogenesis and neurogenesis through activation of brain derived neurotrophic factor (BDNF), which contributes to the infrastructure of brain function through environmental support by promoting new synaptic and neuronal growth.
Concussions & Traumatic Brain Injuries
There are several mechanisms known to be triggered by photons of NIR light which can reduce inflammation, constrain ROS damage, and activate ATP production in energy compromised brain area affected by TBI. Continuous production of ATP is required for successful coordination of metabolic, synaptic and immune efforts to consolidate the area of injury, facilitate recovery and manage local immune response. Moreover, RLT-initiated neurogenesis and synaptogenesis promote reestablishment of axonal connectivity and rebuild the intrinsic nervous networks damaged in TBI.
This approach is supported by literature to be quite effective in acute and chronic TBI treatment, considering general safety and demonstrated efficacy of tPBM light stimulation in-vitro, in-vivo and growing number of recent human clinical trials in this field. One of the first clinical trials (small cohort study) using tPBM light stimulations to treat chronic and mild TBI reported positive improvements in cognition, behavior, and sleep of patients, but also suggested that more robust placebo-controlled studies are needed to ensure reliability of tPBM light in TBI treatment.
There has been an increasing understanding of the link between the gut microbiome, the enteric nervous system and a number of diseases, such as kidney disease, liver disease and cardiovascular disease. Acknowledgement of the importance of the gut–brain axis has increased the recognition of the link between microbiome balance and brain function. It is appreciated that some bacteria that compose the gut microbiome are associated with a range of behavioral dysfunctions and neurodegenerative diseases. This is especially true in Parkinson’s disease (PD).
For example, dysbiosis of the gut microbiome can reduce the number of short chain fatty acid (SCFA) producing bacteria, which in turn increases local inflammatory signaling. Reduction in SCFA production, reduced gastrointestinal functional and anatomical integrity and a consequent increase in the movement of bacterial metabolites (e.g., lipopolysaccharide) across the gut wall are all features of PD, resulting in increased inflammation.
To date, four non-pharmacotherapeutic interventions have been suggested to slow the progression of PD via manipulation of the microbiome, which include diet, pro- and prebiotics, antibiotics and fecal microbiota transplant. Based on recent research, red light therapy (RLT) is a potential novel fifth intervention and may complement new and existing treatment strategies.
As a potential therapy, RLT would ideally be commenced as early as possible in the disease trajectory, before severe reduction or complete elimination of beneficial bacteria from the microbiome (including medications) and may best be combined with diet, pre- and probiotics or fecal microbiota transplant to restore microbiome genera.
What does the research show?
“Aging is a multifactorial biological process, characterized by a decline in physiological functions, including brain functions. Studies with animals and humans show that PBM can improve cognitive function during this phase of life… Moreover, there is no evidence in the literature that PBM adversely affects brain activity in healthy older adults and patients with brain damage. Thus, we can consider PBM to be a promising strategy for treating the cognitive deficits observed during aging.” (1)
(RLT for concussions): "The results found an alteration in the cerebral blood flow as well as a consequent increase of the cerebral oxygenation that helped to improve the cerebral function." (2)
(RLT for autism): “A relevant reduction in noncompliant behavior and in parental stress have been found. Moreover, a reduction in behavioral and cognitive rigidity was reported as well as an improvement in attentional functions and in sleep quality.” (3)
“In conclusion, gut flora-targeted PBM provides a new possible non-invasive prevention and treatment method for the treatment of Alzheimer’s disease (AD), and provides a new hope for AD patients.” (4)
“After 8 weeks of PBM treatments, increased brain volumes, improved functional connectivity, and increased cerebral perfusion and improvements on neuropsychological test scores were observed.” (5)
"Transcranial laser therapy (TLT) showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function. These studies suggest that TLT is a potential candidate for treatment of Alzheimers disease.” (6)
"This treatment (near-infrared light) also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to photobiomodulation as a possible therapeutic strategy for the treatment of Parkinson's Disease & other related synucleinopathies." (7)
"Transcranial LLLT has been shown to significantly improve outcome in acute human stroke patients when applied approximately 18 hours after the stroke occurs over the entire surface of the head, regardless of the stroke location." (8)
"These results suggest that LLLT could be applied in cases of general cognitive impairment in elderly persons." (9)
**While the current scientific research seems to indicate many positive benefits of RLT in relation to brain and nerve health, there is still an appreciable necessity for more extensive research to be conducted in this area, including double-blind RCT (randomized controlled trials), to provide a more comprehensive, robust overview that will further elucidate the optimal parameters and appropriate uses of RLT, which will ultimately lead the most safe and efficacious uses for individuals dealing with brain and nerve disorders.
(1) Cardoso, Fabrízio Dos Santos et al. “Photobiomodulation for the aging brain.” Ageing research reviews vol. 70 (2021): 101415. doi:10.1016/j.arr.2021.101415
(2) Carneiro AMC, Poiani GC, Zaninnoto AL, Lazo Osorio R, Oliveira ML, Paiva WS, Zângaro RA. Transcranial Photobiomodulation Therapy in the Cognitive Rehabilitation of Patients with Cranioencephalic Trauma. Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):657-666. doi: 10.1089/photob.2019.4683. PMID: 31647777; PMCID: PMC6818475.
(3) Pallanti, Stefano et al. “Transcranial Photobiomodulation for the Treatment of Children with Autism Spectrum Disorder (ASD): A Retrospective Study.” Children (Basel, Switzerland) vol. 9,5 755. 20 May. 2022, doi:10.3390/children9050755
(4) Chen, Qianqian et al. “Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model.” Journal of photochemistry and photobiology. B, Biologyvol. 216 (2021): 112152. doi:10.1016/j.jphotobiol.2021.112152
(5) Chao, Linda L et al. “Changes in Brain Function and Structure After Self-Administered Home Photobiomodulation Treatment in a Concussion Case.” Frontiers in neurology vol. 11 952. 8 Sep. 2020, doi:10.3389/fneur.2020.00952
(6) De Taboada, Luis & Yu, Jin & El-Amouri, Salim & Gattoni-Celli, Sebastiano & Richieri, Steve & McCarthy, Thomas & Streeter, Jackson & Kindy, Mark. (2011). Transcranial Laser Therapy Attenuates Amyloid-beta Peptide Neuropathology in Amyloid-beta Protein Precursor Transgenic Mice. Journal of Alzheimer's disease : JAD. 23. 521-35. 10.3233/JAD-2010-100894.
(7) Oueslati A, Lovisa B, Perrin J, Wagnières G, van den Bergh H, Tardy Y, Lashuel HA (2015) Photobiomodulation suppresses alpha synuclein-induced toxicity in an AAV-based ratgeneticmodelofParkinson ’s disease. PLoS One 10(10): e0140880
(8) Lampl Y, Zivin JA, Fisher M, et al. Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1). Stroke. 2007; 38:1843–1849.
(9) Michalikova S, Ennaceur A, van Rensburg R, et al. Emotional responses and memory performance of middle-aged CD1 mice in a 3D maze: effects of low infrared light. Neurobiol Learn Mem. 2008; 89:480–488.