J Neuroinflammation. 2012 Sep 18;9(1):219. [Epub ahead of print]
Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases.
Activated microglial cells are an important pathological component in brains of patients with neurodegenerative diseases. The purpose of this study was to investigate the effect of He-Ne (632.8 nm, 64.6 mW/cm2) low-level laser therapy (LLLT), a non-damaging physical therapy, on activated microglia, and the subsequent signaling events of LLLT-induced neuroprotective effects and phagocytic responses.
To model microglial activation, we treated the microglial BV2 cells with lipopolysaccharide (LPS). For the LLLT-induced neuroprotective study, neuronal cells with activated microglial cells in a Transwell[trade mark sign] cell-culture system were used. For the phagocytosis study, fluorescence-labeled microspheres were added into the treated microglial cells to confirm the role of LLLT.
Our results showed that LLLT (20 J/cm2) could attenuate toll-like receptor (TLR)-mediated proinflammatory responses in microglia, characterized by down-regulation of proinflammatory cytokine expression and nitric oxide (NO) production. LLLT-triggered TLR signaling inhibition was achieved by activating tyrosine kinases Src and Syk, which led to MyD88 tyrosine phosphorylation, thus impairing MyD88-dependent proinflammatory signaling cascade. In addition, we found that Src activation could enhance Rac1 activity and F-actin accumulation that typify microglial phagocytic activity. We also found that Src/PI3K/Akt inhibitors prevented LLLT-stimulated Akt (Ser473 and Thr308) phosphorylation and blocked Rac1 activity and actin-based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway.
The present study underlines the importance of Src in suppressing inflammation and enhancing microglial phagocytic function in activated microglia during LLLT stimulation. We have identified a new and important neuroprotective signaling pathway that consists of regulation of microglial phagocytosis and inflammation under LLLT treatment. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.
Postepy High Med Dosw (Online). 2011 Feb 17;65:73-92.
The role of biological sciences in understanding the genesis and a new therapeutic approach to Alzheimer’s disease.
Tegowska E, Wosinska A.
Zaklad Toksykologii Zwierz?a, Wydzial Biologii i Nauk o Ziemi, Uniwersytet Mikolaja Kopernika w Toruniu.
The paper contrasts the historical view on causal factors in Alzheimer’s disease (AD) with the modern concept of the symptoms’ origin. Biological sciences dealing with cell structure and physiology enabled comprehension of the role of mitochondrial defects in the processes of formation of neurofibrillary tangles and ?-amyloid, which in turn gives hope for developing a new, more effective therapeutic strategy for AD. It has been established that although mitochondria constantly generate free radicals, from which they are protected by their own defensive systems, in some situations these systems become deregulated, which leads to free radical-based mitochondrial defects. This causes an energetic deficit in neurons and a further increase in the free radical pool. As a result, due to compensation processes, formation of tangles and/or acceleration of ?-amyloid production takes place. The nature of these processes is initially a protective one, due to their anti-oxidative action, but as the amount of the formations increases, their beneficial effect wanes. They become a storage place for substances enhancing free radical processes, which makes them toxic themselves. It is such an approach to the primary causal factor for AD which lies at the roots of the new view on AD therapy, suggesting the use of methylene blue-based drugs, laser or intranasally applied insulin. A necessary condition, however, for these methods’ effectiveness is definitely an earlier diagnosis of the disease. Although there are numerous diagnostic methods for AD, their low specificity and high price, often accompanied by a considerable level of patient discomfort, make them unsuitable for early, prodromal screening. In this matter a promising method may be provided using an olfactory test, which is an inexpensive and non-invasive method and thus suitable for screening, although as a test of low specificity, it should be combined with other methods. Introducing new methods of AD treatment does not mean abandoning the traditional ones, based on enhancing cholinergic transmission. They are valuable as long as the therapy starts when abundant brain inclusions disturb the transmissions.<br />
Long-term safety of single and multiple infrared transcranial laser treatments in Sprague-Dawley rats.
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BACKGROUND AND OBJECTIVE:
Growing interest exists in the use of near-infrared laser therapies for the treatment of numerous neurologic conditions, including acute ischemic stroke, traumatic brain injury, Parkinson’s disease, and Alzheimer’s disease. In consideration of these trends, the objective of this study was to evaluate the long-term safety of transcranial laser therapy with continuous-wave (CW) near-infrared laser light (wavelength, 808?±?10?nm, 2-mm diameter) with a nominal radiant power of 70?mW; power density, 2,230?mW/cm(2), and energy density, 268?J/cm(2) at the scalp (10?mW/cm(2) and 1.2?J/cm(2) at the cerebral cortical surface) in healthy Sprague-Dawley rats.
MATERIALS AND METHODS:
In this study, 120 anesthetized rats received sequential transcranial laser treatments to the right and left parietal areas of the head on the same day (minimum of 5?min between irradiation of each side), on either Day 1 or on each of Days 1, 3, and 5. Sixty anesthetized rats served as sham controls. Rats were evaluated 1 year after treatment for abnormalities in clinical hematology and brain and pituitary gland histopathology.
No toxicologically important differences were found in the clinical hematology results between sham-control and laser-treated rats for any hematologic parameters examined. All values fell within historic control reference ranges for aged Sprague-Dawley rats. Similarly, brain and pituitary gland histopathology showed no treatment-related abnormalities or induced neoplasia.
Single and multiple applications of transcranial laser therapy with 808-nm CW laser light at a nominal power density of 10?mW/cm(2) at the surface of the cerebral cortex appears to be safe in Sprague-Dawley rats 1 year after treatment.
The Efficacy of 904 nm Laser Therapy for Alzheimer’s Diseases
Kazuyoshi Zenba, Vice president of Kanagawa Acupuncture Massage Association
Prof. Masayuki Inoue, Secretary of JLPLTPA
Although we had reported about the possible efficacy of low power laser therapy (LPLT) for Senile Dementia(S D) 3 times from 1993 at the annual meetings of Japan Society for Laser Medicine, there was no practically useful treatment found for Alzheimer’s disease(AD) and Parkinson disease and other Senile Dementia even after the start of elderly-care-insurance system in Japan. As we have continued above said laser therapy for SD at home care visit of elderly persons and felt very useful and effective, we would like to report about recent situation of laser therapy for AD patients.
Especially recently, the number of Alzheimer’s disease patients is increasing by the arrival of super-aged world in Japan. However the cause of this disease is not known and there is no effective treatment established at present. As to the mechanism of LPLT, its main mechanism is mostly elucidated by the progress in the field of Molecular biology and widely used for the removal of pain, decrease of swelling and treatment of wound. However its application for the treatment of Brain diseases is hardly practiced.
We have continued the treatment of Senile Dementia patients by LPL considering it as to be one of practical and effective treatment of this disease
LPLT is very useful for the medical treatment of the senile dementia patients at home for the expansion of ADL, pain relief, mitigation of inflammation, prevention of bed sore, the treatment of hemiplegia in a brain blood vessel obstacle and the braking of aggravation of Alzheimer’s disease without any fear of side effects by the irradiation of LPL to the head of patients.
It will be not to exaggerate to say LPLT can be one of main treatments of senior patients at home in near future.
(Object of study)
To study the practical usefulness of LPLT for the treatment of Alzheimer’s disease patients at home in terms of improvement of ADL and QOL and also for the reduction of burden of families of the care of patients.
(Method of treatment)
15 Alzheimer’s disease patients, 5 male and 10 female, received irradiation of LPL for 2 minutes at each points, 2-3 times a week for one year. Laser irradiation points were as follows. Acupuncture points established as effective based on long history of Oriental medicine .
(1) Acupuncture point to improve blood circulation (2) Acupuncture point for the treatment of stroke (3) Acupuncture point for adjustment of blood pressure (4) Acupuncture point for adjustment of balance of autonomous nerve.( the forehead, the right and left temple, occiput)
In addition, the method (based on papers in Russia and Armenia that intravenous LPL irradiation improved the viscosity of blood) of irradiating LPL to the place which touches the pulse of an artery under collarbone was used as an additional medical treatment point.
Among evaluation items, cooperativeness and the lack of composure were observed as useful as an effect, the effect appeared half a year after and continued after one year and later on.
It was suggested that LPLT was useful for the improvement of orientation disturbance, normalization of clothing and the dress. Because, many families and the care workers talked us LPL was very helpful since the present condition could be maintained, without getting worse.
After the start of LPL treatment, It was reported that the coldness of hands and legs of patients vanished and joints and muscular stiffness were also mitigated. Therefore, the joint movable region was also secured comparatively.
Also in excretion care, it became very easy to carry out the care of patients.
It was able to say about all patients that their expression became quiet and came to show understanding to directions of a care worker. It is suggested by this that LPLT as one of practical treatment of patients at home by the improvement of care power at home.
Since the senile-dementia-of-Alzheimer-type has a feature of advance of condition and it was said that condition became gradually critical, we tried this treatment expecting the maintenance of condition, and examination whether there was any delay effect. It is considered to have been suggested at least there was an effect of maintaining present condition in a certain field.
About the effect over the brain of laser irradiation, it was reported at the annual meeting of Japan Society for Laser Surgery and Medicine meeting in 1991 by Jun-Ichi Nishimura et al., of Department of Physiology, Yokohama City University School of Medicine. The 780 nm wavelength and 1mW laser irradiation to the inner core of rats made the increase of cerebral blood flows at hippocampus by the amount of about 20% in average (control:15, laser:15). Although after 30 minute it was confirmed having maintained the increase of 10%.
In 1992 at the same medical conference, Takayuki Obata et. al., of the same University reported that laser irradiation of 780nm wavelength10mW to the head surface of rats activated cranial nerves activities (control:16, laser:15).
These reports suggested the possible usefulness of LPL treatment to Senile Dementia and other brain diseases patients. Unfortunately these findings did not much attention of medical world In Japan.
However, recently a possibility that ATP and cellmembrane potential of brain neuron could be controlled specifically by the irradiation of near infrared lasers (830nm wavelength) on the surface of heads of rats was reported by Oda-Mochizuki etc.al.?Ritsumeikan University, Synchrotron Light Life Science Center.
It was suggested by this research center that the condition of Epilepsy could be stabilized by Irradiating infrared laser from out side of heads of patients and decreasing the unusual excitement of cerebral neurons and in case of cerebral infarction, the aggravation of progress of Necrosis and Apotosis of cerebral neurons could be stopped by making stabilize the electric potential of cell membrane of cerebral neurons.
Development of future research in this field is expected as what supports scientifically the medical treatment of LPL and the result of condition improvements, such as Senile Dementia, brain blood vessel obstacles, hemiplegia and Parkinson patients.
Although the wavelength of LPL used for “Examination of the validity of LPL to Senile Dementia Patients” which we announced at the annual meetings of Japan Society for Laser Surgery and Medicine meeting over three years from 1993, was 780nm and out put was10mW, and 1mw. The LPL used for this examination was of the wavelength of 904nm and the peak value of a pulse was 5W and the average output was 5mW. However, the same medical treatment effect was confirmed. Although it is thought that there was no wavelength dependability of laser to the efficacy over the Alzheimer’s diseases of LPL(780,830,904nm lasers are equally effective for pain removal and wound healing), how is it sure enough? A question remains.
By this examination, at least following effects were confirmed. Namely (1) the advance of condition of Alzheimer’s diseases has been blocked (2) and the expression of patients changed to smiling from disinterestedness, cooperativeness came out , an understanding came to be shown to a partner (3) We received comments from many families that the care of patients became much easier than before. It is considered that the head irradiation of near infrared laser light makes the cerebral blood flow improve, activates nerve activities and have applied brakes to the advance of the apotosis of brain cells as animal experiments are proving. Since the medical treatment efficacy is seldom acknowledged to middle degree class and a serious patient, although it is hard to call it the fundamental cure for Alzheimer’s disease by the present method, if medical a treatment is started in early stage and continued, it may be possible to call it one of practical cures which can stop subsequent advance of disease.
Based on this experience, collecting newest information overseas, research results in the biology field, we will continue to study the possible LPL method for the dramatic cure of Alzheimer’s diseases by changing the wavelength of laser, the output and the irradiation method and also combination with other therapies