Stress-free Therapy Research Center, Ryotokuji University.
BACKGROUND AND AIMS: The incidence of vascular dementia (VD) and Alzheimer's disease (AD) has recently increased and the prevention of progression of these diseases is very difficult.
RESULTS: The application of pinpoint plantar long-wavelength infrared light irradiation (PP-LILI) to a patient's sole, at the point where the line drawn between the first and second metatarsal heads intersects with the vertical line from the medial malleolus, was effective in increasing blood flow to the facial artery, elevating high- density lipoprotein cholesterol (HDL-C) levels, and reducing insulin resistance.
CONCLUSIONS: We found that these effects of PP-LILI might be helpful for preventing VD and AD, conditions that are becoming a social problem in an aging Japanese society.
Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Low-level laser therapy (LLLT) has been used to treat inflammation, tissue healing, and repair processes. We recently reported that LLLT to the bone marrow (BM) led to proliferation of mesenchymal stem cells (MSCs) and their homing in the ischemic heart suggesting its role in regenerative medicine. The aim of the present study was to investigate the ability of LLLT to stimulate MSCs of autologous BM in order to affect neurological behavior and beta-amyloid burden in progressive stages of Alzheimer's disease (AD) mouse model. MSCs from wild-type mice stimulated with LLLT showed to increase their ability to maturate towards a monocyte lineage and to increase phagocytosis activity towards soluble amyloid beta (Abeta). Furthermore, weekly LLLT to BM of AD mice for 2 months, starting at 4 months of age (progressive stage of AD), improved cognitive capacity and spatial learning, as compared to sham-treated AD mice. Histology revealed a significant reduction in Abeta brain burden. Our results suggest the use of LLLT as a therapeutic application in progressive stages of AD and imply its role in mediating MSC therapy in brain amyloidogenic diseases.
Bosch Institute, University of Sydney NSW 2006, Australia. Daniel.Johnstone@sydney.edu.au
INTRODUCTION: Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer's disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at an age when substantial pathology is already present in the cerebral cortex.
METHODS: We studied two mouse models with AD- related pathologies: the K369I tau transgenic model (K3), engineered to develop neurofibrillary tangles, and the APPswe/PSEN1dE9 transgenic model (APP/PS1), engineered to develop amyloid plaques. Mice were treated with NIr 20 times over a four-week period and histochemistry was used to quantify AD- related pathological hallmarks and other markers of cell damage in the neocortex and hippocampus.
RESULTS: In the K3 mice, NIr treatment was associated with a reduction in hyperphosphorylated tau, neurofibrillary tangles and oxidative stress markers (4-hydroxynonenal and 8-hydroxy-2'- deoxyguanosine) to near wildtype levels in the neocortex and hippocampus, and with a restoration of expression of the mitochondrial marker cytochrome c oxidase in surviving neurons. In the APP/PS1 mice, NIr treatment was associated with a reduction in the size and number of amyloid-beta plaques in the neocortex and hippocampus.
CONCLUSIONS: Our results, in two transgenic mouse models, suggest that NIr may have potential as an effective, minimally-invasive intervention for mitigating, and even reversing, progressive cerebral degenerations.
Department of Physiology (Neuroscience Program), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; Integrative Complementary Alternative Medicine Research and Development Group, Khon Kaen University, Khon Kaen, Thailand.
The burden of Alzheimer's disease is continually rising globally, especially in the Asia-Pacific region. Unfortunately, the efficacy of the therapeutic strategy is still very limited. Because the effect of acupuncture at HT7 can improve learning and memory, the beneficial effect of laser acupuncture, a noninvasive form of acupuncture, at HT7 on memory improvement in patients with Alzheimer's disease has been a focus of research. To elucidate this issue, we used AF64A, a cholinotoxin, to induce memory impairment in male Wistar rats, which weighed 180-220 g. Then, the animals were treated with laser acupuncture either at HT7 or at a sham acupoint once daily for 10 minutes for a period of 14 days.
Spatial memory assessments were performed at 1, 7, and 14 days after AF64A administration and at the end of the experiment, and the changes in the malondialdehyde (MDA) level and in the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in the hippocampus were recorded. The results showed that laser acupuncture significantly suppressed AChE activity in the hippocampus. Although laser acupuncture enhanced SOD and CAT activities, no reduction in MDA level in this area was observed. Therefore, laser acupuncture at HT7 is a potential strategy to attenuate memory impairment in patients with Alzheimer's disease. However, further research, especially on the toxicity of laser acupuncture following repetitive exposure, is essential.
MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low- level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via upregulation of BDNF in both Abeta-treated hippocampal neurons and cultured APP/PS1 mouse hippocampal neurons. Photoactivation of transcription factor CRE-binding protein (CREB) increased both BDNF mRNA and protein expression, since knockdown CREB blocked the effects of LLLT. Furthermore, CREB-regulated transcription was in an ERK-dependent manner. Inhibition of ERK attenuated the DNA-binding efficiency of CREB to BDNF promoter. In addition, dendrite growth was improved after LLLT, characterized by upregulation of Rac1 activity and PSD-95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT by activation of ERK/CREB pathway can ameliorate Abeta-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Abeta-induced neurotoxicity.
Our research may provide a feasible therapeutic approach to control the progression of AD. J Neurosci 2013 Aug 14 33(33) 13505-17
1 Institute of Micro and Nanomaterials, Nanobionic Laboratory, University of Ulm , Ulm, Germany .
Abstract Objective: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer's disease (AD).
Background Data: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra- and intracellular deposition of amyloid-beta (Abeta) fibrils in the brain. Recently, it was shown that extracellular Abeta can enter brain cells, resulting in neurotoxicity.
Methods: After internalization of Abeta(42) into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm (-2)) and/or treated with epigallocatechin gallate (EGCG).
Results: In irradiated cells, Abeta(42) aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCG-treated cells, Abeta(42) aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with Abeta(42) and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in Abeta(42)-free cells, when compared to nonirradiated cells. Laser- induced clearance of Abeta(42) aggregates occurred at the expense of cellular ATP.
Conclusions: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Abeta aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD.
Abstract
Regenerative capacity following injury or an ischemic event is confined to non mammalian vertebrates. Mammals have a limited capacity to restore organs
following injury to organs like the liver and skeletal muscles but practically no ability to regenerate organs like the heart or brain following an ischemic event
or injury. We tried a new approach in cell based therapy to improve regeneration in various organs following ischemic injury. Low-level laser therapy (LLLT)
which has photobiostimulating effects on cells was delivered to autologous bone marrow (BM) that is enriched with stem cells and various progenitor cells, in
order to induce the cells in the BM for the benefit of the injured /ischemic organs. In a model of induced myocardial infarction (MI) in rats laser application
to the BM caused a marked and significant decrease (79%) in infarct size (scarring) 3 weeks post-MI. It was also found that a significantly higher density of
c-kit positive cells (a marker of mesenchymal stem cells) in the myocardium of laser-treated rats relative to non-treated rat’s post-MI. The novel approach
presented in this study, of the use of stem cells for cell therapy to the infracted heart, avoids the need to isolate millions of stem cells, to grow them in vitro and
to inject them back into the patient. In the same line of rationale we tried to find whether LLLT to the BM could be beneficial also to kidney impairment after
ischemic reperfusion injury (IRI) to the rat kidney. C-kit positive cell density in kidneys post-IRI and laser-treatment was significantly (p=0.05) 2.4-fold higher
compared to the non laser treated group. Creatinine, blood urea nitrogen, and cystatin-C levels were significantly lower in the laser-treated rats as compared
to non-treated ones. The effect of LLLT delivery to BM was also tested on Alzheimer’s disease (AD) mice in their late stage of the disease. Mice were given
multiple (every 10 days) LLLT to BM from age 4 to 6 months. It was found that in the treated AD-mice neurological tests (Fear and Cognitive tests) revealed
a significantly (p<0.05) better neurological performance and cognitive capacity compared to the non-treated AD mice. Furthermore, concomitantly with the
improved neurological performance, ß-amyloid density in the hippocampal region of the brains was revealed to be significantly less in the laser-treated mice
as compared to control. In conclusion, a novel approach, of applying LLLT to autologeous BM in order to induce stem cells that are consequently recruited to the
injured/ischemic organ leading to a marked beneficial effect post-ischemic event or degenerative process is presented. This approach is novel in the respect
that it is stimulating the patient’s own abilities to initiate a regenerative response in an organ by the utilization of light. The possibility that this approach can
also be applied to other ischemic/injured organs or organs undergoing degenerative processes (i.e. neurodegenerative diseases), with consequent beneficial
effects, cannot be ruled out
CELL THERAPY FOR INJURED/ISCHEMIC ORGANS
Clinical trials have lately been implemented in a growing
abundance due to the extensive research and new approaches of
cell based therapies for the reconstruction of impaired organs.
Regenerative capacity following injury or an ischemic event
is confined to non mammalian vertebrates. In particular, fish
and primitive amphibians can regenerate organs like the heart,
brain and limbs. However, mammals have a limited capacity
to restore organs following injury to organs like the liver and
skeletal muscles but practically no ability to regenerate organs
like the heart or brain following an ischemic event or injury.
The mammalian heart, including the human heart, for example,
has a very limited capacity to regenerate following damage or
an acute ischemic event like myocardial infarction (MI). This is
due to the very low level of cardiomyocyte proliferation and the
limited number of cells expressing stem-cell marker proteins.
Stem-cell-based therapy was suggested as a potential solution
to the above situation. In recent years, cell-based therapy for
cardiac repair in particular has undergone a rapid transition
from basic science research to clinical reality [1-3]. The general
outcome of the clinical trials was that the procedures and longterm
outcome post-stem-cell implantation to the heart via the
coronary arteries are safe. However, improvement in long-term
functional performance of the heart was either not achieved or
was marginal [1-3].
There are several central issues pertaining to the use of cell
implantation in stem-cell therapy: the number of implanted stem
cells has to be high since there is massive cell death following
implantation or injection of cells into the heart or the blood
circulation. Another central issue in stem-cell implantation for
organ repair is the creation of a receptive cell environment in the
ischemic organ. Several factors (e.g. inhibition of inflammation
and apoptosis, secretion of cell growth factors etc.) are necessary
for optimal cell implantation [4]. The injected cells may have to
migrate from the circulating blood to the ischemic niche. They
can then remain active and secrete growth factors, exerting a paracrine effect on the ischemic tissue [5]. Alternatively, they
may stimulate the small population of stem cells in the ischemic
organ (such as the heart), to proliferate and differentiate so as to
enhance cardiac repair post-MI [6]. Another issue is the timing
of injection of the stem cells to the infarcted heart and effect of
MI (inflammatory phase) on the BM [7]. Photobiostimulation
of cells in the bone marrow (BM), that is enriched with various
progenitor cells, by low level laser therapy (LLLT) may suggest a
new approach that may overcome some of the above limitation.
This new approach will be discussed in the present mini review
[8-11].
LOW LEVEL LASER THERAPY FOR THE ISCHEMIC
HEART
In general LLLT has been found to modulate various biological
processes, such as increasing mitochondrial respiration and ATP
synthesis, facilitating wound healing, and promoting the process
of skeletal muscle regeneration and angiogenesis [12,13]. It
was previously shown that LLLT can enhance skeletal muscle
regeneration following partial excision in the rat hind limb
muscles when the laser was delivered directly to the injured
organ multiple times (for 2 min each time) following injury [14].
This phenomenon was even more prominent following cold
injury to the frog skeletal muscles indicating that enhancement
of regeneration by LLLT is probably a general phenomenon in
vertebrates and maybe more effective in cold blooded animals
which innately have a lower metabolic rate in their cells [13-15].
In an experimental model of the infarcted heart in rats and dogs, it
was demonstrated that LLLT (Diode –Ga-Al-As 810nm at a power
density of 5 mW/cm2 for 120sec duration of laser exposure
comprising 0.6 J/cm2), application directly to the infarcted area
in the heart at optimal power parameters significantly reduces
infarct size (scar tissue formation) [16,17]. This phenomenon
was partially attributed to a significant elevation in ATP content,
heat shock proteins, vascular endothelial growth factor (VEGF),
and angiogenesis in the ischemic zone of the laser-irradiated
rats, as compared to non-irradiated rats [16,17]. The mechanism
associated with the photobiostimulation by LLLT is not yet
clearly understood [12]. There is evidence that cytochrome c
oxidase and perhaps also plasma membranes in cells function as
photoacceptors of the photons, and thereafter a cascade of events
occur in the mitochondria, leading to effects on various processes
like ATP production, up-regulation of VEGF, etc [12].
The effect of photobiostimulation on stem cells or progenitor
cells has not been extensively studied [18-21]. It was previously
shown that laser application (Diode laser at 50mW/cm2 for
100sec, energy density 0.5 mW/cm2) to the mesenchymal stem
cells isolated from bone marrow or cardiac stem cells causes a
significant increase in their proliferation in vitro [20]. Based on
previous studies that showed an increase in cytoprotective effect
on the ischemic heart following LLLT, a new approach was taken
to apply laser irradiation to stem cells grown in culture prior
to their implantation to the infarcted heart as a cell therapy for
heart repair [21]. In that study it was demonstrated that MSCs
that were laser treated prior to their implantation to the rat
infarcted heart caused a significant reduction in infarct size
as compared to MSCs that were injected to the heart without
prior laser treatment. This phenomenon was also associated
with significant elevation of vascular endothelial growth factor
(VEGF) in the myocardium of the rats that received the lasertreated
MSCs. In a recent study [8] the possibility of recruiting
autologous stem cells stimulated by LLLT in the BM to the
infarcted heart was addressed. The rationale behind the attempt
to use LLLT to induce the “crude” BM in the bone was, and still is,
that one cannot significantly affect the complex process post-MI
or ischemic injury to the kidney with a single type of stem cell. The
native BM is known for its many types and subtypes of stem cells,
which are defined by their reactivity to various antibodies. The
BM also contains many progenitor cells (i.e. monocytes) that can
further differentiate, for example to macrophages. Macrophages
have been shown recently to have a crucial role in the scarring
process post-MI. Thus LLLT may induce concomitantly in the BM
various types of cells that will increase in number in the blood
circulation following their enhanced proliferation in the BM.
These cells will probably, eventually, and to a certain extent and
under certain circumstances, home in on the ischemic zone in the
ischemic organ (heart, kidney etc.). In this study [8] it was found
that when LLLT was applied in vivo to the BM, and MSCs were
isolated from that BM 3 and 6 weeks later and grown in vitro, they
grew at a higher rate of proliferation relative to MSCs isolated
from non-laser-treated BM. This indicated that the MSCs when
in the BM, following LLLT application in vivo can be induced to
proliferate to a higher rate than non-treated MSCs. Furthermore,
laser application (Diode laser 808nm at power density of 10mW/
cm2 for 100 sec comprising 1J/cm2 energy density) to the BM (at
about 20 min post-MI) caused a marked and significant decrease
(79%) in infarct size 3 weeks post-MI. This extent of infarct size
reduction was even more effective in reducing scarring than that
of laser application directly to the infarcted heart, as also found
in previous studies with infarcted rat and dog hearts [10]. Even
when laser was applied 4 hours post-MI to the BM of infarcted
rats, a marked and significant reduction in the infarcted area
was observed in the laser-treated rats compared to control.
We also found a significantly higher density of c-kit+ (a marker
of MSCs) cells in the myocardium of laser-treated rats relative
to non-treated rat’s post-MI. Moreover, it was demonstrated in
this study that c-kit+ cells post-laser application to the BM of MIinduced
rats, homed specifically in on the infarcted heart and
not on uninjured organs (i.e. liver, kidney) in the same rat [16].
It can be hypothesized that the increased number of c-kit+ cells
found in the myocardium came from proliferating MSCs in the
BM that had migrated to the circulating blood and homed onto
the infarcted heart. Another finding of this study was that of
the preferred homing of the recruited or endogenous c-kit+ cells
in on the infarcted area, rather than their random deposition
throughout the left ventricle in the heart. Indeed, at 3-weeks
post-MI the density of c-kit+ cells in the infarcted area was 27-
fold higher in the rats whose BM had been treated with LLLT as
compared to control rats. Similarly, Hatzistergos et al. [6] found
that endogenous c-kit+ cardiac stem cells increased by 20-fold
in the porcine infarcted heart as compared to control following
This tool is a searchable collection of technical publications, books, videos and other resources about the use of lasers and light for PhotoBioModulation (PBM). Enter a keyword above or see some of our favorite queries below.
Here are some of our favorite queries:
All the resources include links to the original source so we are not making any statement about the use of lasers for treating non-FDA cleared application, we are simple summarizing what others have said.
Where every possible, we have included a link to the orginal publication.
This tool uses a broad match query so:
The results of the search are sorted based on 3 quality factors on a scale of 1 to 10 with 10 being the best score. Originally all the resources were given a 5-5-5 until they could be individually evaluated. These scores are purely opinion and are only used to simplify the rank of the results from more valuable to least valuable. This should not be considered a critique of any work. This system was created to help researchers (including ourselves) find the most usable resources for any cold laser therapy research. The resources are assigned values based on the following 3 factors:
Over the past few years of working with research, we found that a majority of the published resources are lacking in one of these three ranking factors.
The original goal of this research tool was to tie published resources to the protocols in the laser-therapy.us library. This connection allows users to trace each protocol back to a list of resources so the protocol can be researched and improved.
General Comments
POWER
When many of the first research papers were published, the most power laser available for therapy were less than 100mW and many systems had to be pulsed to keep the laser from burning out too quickly. Today, system are available that will deliver up to 60,000mW of continuous output. Because of these power limitation, many early studies were limited to extremely low dosages by today’s standards. It takes a 50mW system 17 minutes to deliver 50 joules at the surface of the skin. If this was spread over a large area of damage or was treating a deeper problem, the actual dosages were much less than 1J/cm2. Today, we know that these dosages typically produce very little or no results.
WAVELENGTH
About 80% of the resources in this database are in the near infrared wavelength. There is also some interest in the red wavelength (600 to 660nm) . Other wavelengths like blue, purple, and green have very little scientific research behind them and have not gotten much traction in the core therapy market with the exception of some fringe consumer products.
Legal Disclaimer
This research tool is free to use but we make no claims about the accuracy of the information. It is an aggregation of existing published resources and it is up to the user to determine if the source of the resources has any value. The information provided through this web site should not be used for diagnosing or treating a health problem or disease. If you have or suspect you may have a health problem, you should consult your local health care provider.
Welcome to the BioPhotonica Education Center. There are over 5000 successful studies showing the efficacy of PBM, light therapy and sound therapy. This is a searchable collection of technical publications, books, videos and other resources about the best practices in the industry and about treating a wide variety of problems. All the resources include links to the original source (where available) so we are not making any claims about the use of our technology for treating "non-FDA cleared" applications, we are simply summarizing what the expert are saying about proper application of these technologies.
Enter a keyword above and click on one of the following links to see a set of publications about that subject. HINT: Shorter keywords work better.
Here are some of our favorite queries:
Testimonials
Research Info for other Applications
Autoimmune Research
Contraindications
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Welcome to the Lighthouse Health Education Center. There are over 5000 successful studies showing the efficacy of PBM, light therapy and sound therapy. This is a searchable collection of technical publications, books, videos and other resources about the best practices in the industry and about treating a wide variety of problems. All the resources include links to the original source (where available) so we are not making any claims about the use of our technology for treating "non-FDA cleared" applications, we are simply summarizing what the expert are saying about proper application of these technologies.
Enter a keyword above and click on one of the following links to see a set of publications about that subject. HINT: Shorter keywords work better.
Here are some of our favorite queries:
Testimonials
Research Info for other Applications
Autoimmune Research
Contraindications
This tool uses a broad match query so: