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Hamblin M.R.,Harvard-MIT Division of Health Sciences and Technology | Huang Y.-Y.,Harvard University | Huang Y.-Y.,Guangxi Medical University | Sharma S.K.,Massachusetts General Hospital | Carroll J.,THOR Photomedicine Ltd.
Dose-Response | Year: 2011

Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments. © 2011 University of Massachusetts. Source

Chung H.,Massachusetts General Hospital | Chung H.,Harvard University | Dai T.,Massachusetts General Hospital | Dai T.,Harvard University | And 8 more authors.
Annals of Biomedical Engineering | Year: 2012

Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term "low level laser therapy" or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy. © 2011 Biomedical Engineering Society. Source

Khuman J.,Harvard University | Zhang J.,Harvard University | Park J.,Harvard University | Carroll J.D.,THOR Photomedicine Ltd. | And 2 more authors.
Journal of Neurotrauma | Year: 2012

Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcomes after experimental traumatic brain injury (TBI), and coherent near-infrared light has been reported to improve cognitive function in patients with chronic TBI. However, the effects of LLLT on cognitive recovery in experimental TBI are unknown. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve post-injury Morris water maze (MWM) performance. Low-level laser light (800nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80min after CCI. Injured mice treated with 60J/cm 2 (500mW/cm 2×2min) either transcranially or via an open craniotomy had modestly improved latency to the hidden platform (p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated controls. The beneficial effects of LLLT in open craniotomy mice were associated with reduced microgliosis at 48h (21.8±2.3 versus 39.2±4.2 IbA-1+ cells/200×field, p<0.05). Little or no effect of LLLT on post-injury cognitive function was observed using the other doses, a 4-h administration time point and 7-day administration of 60J/cm 2. No effect of LLLT (60J/cm 2 open craniotomy) was observed on post-injury motor function (days 1-7), brain edema (24h), nitrosative stress (24h), or lesion volume (14 days). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI. © 2012, Mary Ann Liebert, Inc. Source

Barasch A.,New York Medical College | Barasch A.,University of Amsterdam | Raber-Durlacher J.,University of Amsterdam | Epstein J.B.,Cedars Sinai Medical Center | Carroll J.,THOR Photomedicine Ltd.
Supportive Care in Cancer | Year: 2016

Purpose: Low-level laser therapy (LLLT) efficacy for the prevention of cancer treatment-induced oral mucositis (OM) has been amply described. However, potential protection of malignant cells remains a legitimate concern for clinicians. We tested LLLT-induced protection from ionizing radiation killing in both malignant and normal cells. Methods: We treated six groups each of normal human lymphoblasts (TK6) and human leukemia cells (HL60) with He-Ne LLLT (632.8 nm, 35 mW, CW, 1 cm2, 35 mW/cm2 for 3–343 s, 0.1–12 J/cm2) prior to exposure to ionizing radiation (IR). Cells were then incubated and counted daily to determine their survival. Optimization of IR dose and incubation time was established prior to testing the effect of LLLT. Results: Growth curves for both cell lines showed significant declines after exposure to 50–200 cGy IR when compared to controls. Pre-radiation exposure to LLLT (4.0 J/cm2) followed by 1-h incubation blocked this decline in TK6 but not in HL60 cells. The latter cells were sensitized to the killing effects of IR in a dose-dependent manner. Conclusion: This study shows that pre-IR LLLT treatment results in a differential response of normal vs. malignant cells, suggesting that LLLT does not confer protection and may even sensitize cancer cells to IR killing. © 2015, Springer-Verlag Berlin Heidelberg. Source

Agrawal T.,Massachusetts General Hospital | Agrawal T.,Harvard University | Gupta G.K.,Massachusetts General Hospital | Gupta G.K.,Harvard University | And 6 more authors.
Dose-Response | Year: 2014

Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. © 2014 University of Massachusetts. Source

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