Traumatic Brain Injury (TBI) / Stroke
Dr. Margaret Naeser at Boston University Hospital, Dr. Michael Hamblin at Harvard Medical School and their colleagues continue to do groundbreaking research on the use PBM Therapy on Traumatic Brain Injuries (including stroke) as well as cognitive dysfunction and dementia. The results they are seeing are exceptional and have exciting implications for the future of medicine and the treatment of conditions and diseases that have not had encouraging treatment options, until now.
Naeser MA, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin MR, Knight JA, Meehan WP 3rd, Baker EH., J Neurotrauma. 2014; 31(11):1008-17
This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500mW, 22.2mW/cm(2)) was applied for 10min to each of 11 scalp placements (13J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). 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. This open-protocol data suggest that placebo-controlled studies are warranted.
Cognitive Dysfunction or Dimentia
Significant Improvement in Cognition in Mild to Moderately Severe Dementia Cases Treated with Transcranial Plus Intranasal Photobiomodulation: Case Series Report.
Saltmarche AE1, Naeser MA2,3, Ho KF4, Hamblin MR5,6, Lim L7., Photomed Laser Surg. 2017 Feb 10. doi: 10.1089/pho.2016.4227
This study investigated whether patients with mild to moderately severe dementia or possible Alzheimer's disease (AD) with Mini-Mental State Exam (MMSE) Baseline scores of 10-24 would improve when treated with near-infrared photobiomodulation (PBM) therapy.
Animal studies have presented the potential of PBM for AD. Dysregulation of the brain's default mode network (DMN) has been associated with AD, presenting the DMN as an identifiable target for PBM.
MATERIALS AND METHODS:
The study used 810 nm, 10 Hz pulsed, light-emitting diode devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN (bilateral mesial prefrontal cortex, precuneus/posterior cingulate cortex, angular gyrus, and hippocampus). Five patients with mild to moderately severe cognitive impairment were entered into 12 weeks of active treatment as well as a follow-up no-treatment, 4-week period. Patients were assessed with the MMSE and Alzheimer's Disease Assessment Scale (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial-intranasal PBM device; and daily at-home use of an intranasal-only device.
There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4-week period. This is the first completed PBM case series to report significant, cognitive improvement in mild to moderately severe dementia and possible AD cases.
Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia and AD.
Julio C Rojas1,2, F Gonzalez-Lima1
1Departments of Psychology, Pharmacology and Toxicology, University of Texas at Austin, Austin, TX; 2Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA
Low-level light therapy (LLLT) using red to near-infrared light energy has gained attention in recent years as a new scientific approach with therapeutic applications in ophthalmology, neurology, and psychiatry. The ongoing therapeutic revolution spearheaded by LLLT is largely propelled by progress in the basic science fields of photobiology and bioenergetics. This paper describes the mechanisms of action of LLLT at the molecular, cellular, and nervous tissue levels. Photoneuromodulation of cytochrome oxidase activity is the most important primary mechanism of action of LLLT. Cytochrome oxidase is the primary photoacceptor of light in the red to near-infrared region of the electromagnetic spectrum. It is also a key mitochondrial enzyme for cellular bioenergetics, especially for nerve cells in the retina and the brain. Evidence shows that LLLT can secondarily enhance neural metabolism by regulating mitochondrial function, intraneuronal signaling systems, and redox states. Current knowledge about LLLT dosimetry relevant for its hormetic effects on nervous tissue, including noninvasive in vivo retinal and transcranial effects, is also presented. Recent research is reviewed that supports LLLT potential benefits in retinal disease, stroke, neurotrauma, neurodegeneration, and memory and mood disorders. Since mitochondrial dysfunction plays a key role in neurodegeneration, LLLT has potential significant applications against retinal and brain damage by counteracting the consequences of mitochondrial failure. Upon transcranial delivery in vivo, LLLT induces brain metabolic and antioxidant beneficial effects, as measured by increases in cytochrome oxidase and superoxide dismutase activities. Increases in cerebral blood flow and cognitive functions induced by LLLT have also been observed in humans. Importantly, LLLT given at energy densities that exert beneficial effects does not induce adverse effects. This highlights the value of LLLT as a novel paradigm to treat visual, neurological, and psychological conditions, and supports that neuronal energy metabolism could constitute a major target for neurotherapeutics of the eye and brain.
LLLT or photobiomodulation refers to the use of low-power and high-fluence light from lasers or LEDs in the red to near-infrared wavelengths to modulate a biological function. Cytochrome oxidase is the primary photoacceptor of LLLT with beneficial eye and brain effects since this mitochondrial enzyme is crucial for oxidative energy metabolism, and neurons depend on cytochrome oxidase to produce their metabolic energy. Photon-induced redox mechanisms in cytochrome oxidase cause other primary and secondary hormetic responses in neurons that may be beneficial for neurotherapeutic purposes. Beneficial in vivo effects of LLLT on the eye have been found in optic nerve trauma, methanol intoxication, optic neuropathy, retinal injury, retinitis pigmentosa, phototoxicity, and age-related macular degeneration. Beneficial in vivo transcranial effects of LLLT on the brain have been observed in anoxic brain injury, atherothrombotic stroke, embolic stroke, ischemic stroke, acute traumatic brain injury, chronic traumatic brain injury, neurodegeneration, age-related memory loss, and cognitive and mood disorders. No adverse side effects have been reported in these beneficial applications of LLLT in animals and humans. The authors conclude that LLLT is a safe and beneficial approach, based on scientifically sound mechanisms of action of red to near-infrared light on cytochrome oxidase, with neurotherapeutic promise for a wide range of ophthalmological, neurological, and psychological conditions.