Lasers in Surgery and Medicine
Low-Level Laser Therapy for Closed-Head Traumatic Brain Injury in Mice: Effect of Different Wavelengths
Qiuhe Wu, MD, PhD,1,2,3 Weijun Xuan, MD, PhD,1,2,4 Takahiro Ando, MS,1,5 Tao Xu, MD, PhD,1,2,6 Liyi Huang, MD, PhD,1,2,7 Ying-Ying Huang, MD,1,2,8 Tianghong Dai, PhD,1,2 Saphala Dhital, PhD,1,9 Sulbha K. Sharma, PhD,1 Michael J. Whalen, MD,10 and Michael R. Hamblin, PhD1,2,11,*Abstract
Background and Objectives: Traumatic brain injury (TBI) affects millions worldwide and is without effective treatment. One area that is attracting growing interest is the use of transcranial low-level laser therapy (LLLT) to treat TBI. The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may treat TBI by increasing respiration in the mitochondria, causing activation of transcription factors, reducing inflammatory mediators and oxidative stress, and inhibiting apoptosis.
Study Design/Materials and Methods: We tested LLLT in a mouse model of closed-head TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with continuous-wave 665, 730, 810, or 980 nm lasers (36 J/cm2 delivered at 150 mW/cm2) 4-hour post-TBI and were followed up by neurological performance testing for 4 weeks.
Results: Mice with moderate-to-severe TBI treated with 665 and 810 nm laser (but not with 730 or 980 nm) had a significant improvement in Neurological Severity Score that increased over the course of the follow-up compared to sham-treated controls. Morphometry of brain sections showed a reduction in small deficits in 665 and 810 nm laser treated mouse brains at 28 days.
Conclusions: The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT.
Keywords: photobiomodulation, low-level laser therapy, traumatic brain injury, mouse model, Neurological Severity Score
Photomedicine and Laser Surgery Volume 30, Number 4, 2012
Focal Increase in Cerebral Blood Flow After Treatment with Near-Infrared Light to the Forehead in a Patient in a Persistent Vegetative State
Hiroshi Nawashiro, M.D., D.M.Sc.,1 Kojiro Wada, M.D., Ph.D.,1 Kanji Nakai, M.D., Ph.D.,2 and Shunichi Sato, Ph.D.3
Objective: This study aimed to quantify the cerebral blood flow (CBF) after bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to the forehead in a patient in a persistent vegetative state following severe head injury. Background data: Positive behavioral improvement has been observed following transcranial near-infrared light therapy in humans with chronic traumatic brain injury and acute stroke.
Methods: Single-photon emission computed tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed following a series of LED treatments.
Results: IMP-SPECT showed unilateral, left anterior frontal lobe focal increase of 20%, compared to the pre-treatment value for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days from an array of 23 Ã�Â· 850nm LEDs, 13mW each, held 5mm from the skin, 30 min per session, the power density 11.4mW/cm2; the energy density 20.5 J/cm2 at the skin. The patient showed some improvement in his neurological condition by moving his left arm/hand to reach the tracheostomy tube, post-LED therapy.
Conclusions: Transcranial LED might increase rCBF with some improvement of neurological condition in severely head-injured patients. Further study is warranted.
Photomedicine and Laser Surgery Volume 29, Number 7, 2011Potential for Transcranial Laser or LED Therapy to Treat Stroke, Traumatic Brain Injury, and Neurodegenerative Disease
Margaret A. Naeser, Ph.D., L.Ac.,1,2 and Michael R. Hamblin, Ph.D.3,4,5
Near-infrared (NIR) light passes readily through the scalp and skull and a small percentage of incident power density can arrive at the cortical surface in humans.1 The primary photoreceptors for red and NIR light are mitochondria, and cortical neurons are exceptionally rich in mitochondria.
It is likely that brain cells are ideally set up to respond to light therapy. The basic biochemical pathways activated by NIR light, e.g., increased adenosine-5Ã¢â�¬â�¢-triphosphate (ATP) production, and signaling pathways activated by reactive oxygen species, nitric oxide release, and increased cyclic adenosine monophosphate (AMP) all work together to produce beneficial effects in brains whose function has been compromised by ischemia, traumatic injury, or neurodegeneration. One of the main mechanisms of action of transcranial light therapy (TLT) is to prevent neurons from dying, when they have been subjected to some sort of hypoxic, traumatic, or toxic insult. This is probably because of light-mediated upregulation of cytoprotective gene products such as antioxidant enzymes, heat shock proteins, and anti-apoptotic proteins. Light therapy in vitro has been shown to protect neurons from death caused by methanol,2 cyanide or tetrodotoxin, 3 and amyloid beta peptide.4
Lapchak P A, Wei J, Zivin J A.Transcranial infrared laser therapy improves clinical rating scores after embolic strokes in rabbits.
Stroke. 2004; 35 (8):1985-1988.
In this study the rabbit small clot embolic stroke model (RSCEM) was used to assess whether laser treatment (7.5 or 25 mW/cmÃ�Â²) altered clinical rating scores (behaviour) when given to rabbits beginning 1 to 24 hours post embolisation. Behavioural analysis was conducted from 24 hours to 21 days after embolisation, allowing for the determination of the effective stroke dose (P50) or clot amount (mg) that produces neurological deficits in 50% of the rabbits.
Using the RSCEM, a treatment is considered beneficial if it significantly increases the P50 compared with the control group. In the present study, the P50 value for controls were 0.97Ã�Â±0.19 mg to 1.10Ã�Â±0.17 mg; this was increased by 100% to 195% (P50=2.02Ã�Â±0.46 to 2.98Ã�Â±0.65 mg) if laser treatment was initiated up to 6 hours, but not 24 hours post embolisation (P50=1.23Ã�Â±0.15 mg). Laser treatment also produced a durable effect that was measurable 21 days after embolisation. Laser treatment (25 mW/cmÃ�Â²) did not affect the physiological variables that were measured. This study shows that laser treatment improved behavioural performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable.
Protective Effect Of Low-Level Laser Irradiation On Acupuncture Points Combined With Iontophoresis Against Focal Cerebral Ischemia-Reperfusion Injury In Rats
Dai JY, Ge LB, Zhou YL, Wang L.
Objective: To investigate the effects of low-level laser irradiation on acupuncture points combined with iontophoresis against brain damage after middle cerebral artery occlusion (MCAO) in rats.
Methods: Sixty-nine SD rats were randomly divided into five groups, including normal group, sham operation group, model group, electro-acupuncture group and low-level laser irradiation on acupuncture points combined with iontophoresis group (LLLI group). The cerebral ischemia-reperfusion (I/R) model was established by thread embolism of middle cerebral artery. The rats in the LLLI group, as well as the electroacupuncture group were given treatment as soon as the occlusion finished (0 hour) and 12, 24 hours after the occlusion. We observed the changes of neurological deficit scores and the body weight of the rats at different time. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ratos brain tissue were tested.
Results: The neurological deficit score of the LLLI group was significantly lower than that of the model group. The body weight and the activity of SOD of the rats decreased slightly, and the content of MDA decreased significantly after the treatment.
Conclusion: The low-level laser irradiation on acupuncture points combined with iontophoresis can prevent focal cerebral ischemia-reperfusion injury. One of its mechanisms may be increasing the activity of SOD and decreasing the damage of the oxidation products to the body.
WANG Yu ZHU Jing, et al (Department of Neurosurgery, Renji Hospital Affiliated to Shanghai Second Medical University, Shanghai Medical Centre for laser Research ,200001)
ACTA LASER BIOLOGY SINICA Vol. 8, No.2, 1999
Abstract: To evaluate the effect and mechanism of Vascular Low Level Laser Irradiation Therapy on brain injury. In this study thirty-eight SpragueDawley rats received Feeney's brain impact through a left lateral craniectomy under anesthesia. Control and treatment group are set up. According to the time exposed to laser and irradiating postinjury, the treatment group is divided in four subgroups by design. Semiconductor laser was used with a power of 5mW to irridate straightly Rat's femur venous. The Y Water maze was used to assess cognitive performance. Superoxide dismutase(SOD) activity and the level of metabolic production of free radical MDA in Brain and erythrocyte were measured to determinate the level of free radical.
We find Vascular Low Level Laser Irradiation Therapy can improve posttraumatic memory deficits. SOD activity is higher in treatment groups than the control group meanwhile the level of MDA is lower. These findings suggest that Vascular Low Level Laser Irradiation produced a significant reduction in free radical's damage to the brain postinjury.
E.L. Macheret, A.O. Korkushko, T.N. Kalishchuk, M.N. Matyash
Medical Academy of Post-Diploma Education, Kiev, Ukraine
The examination of 198 patients aged 16-47 has revealed a high frequency of progressive pathologic states in a form of asthenia, vegeto-vascular dystonia, hypertensive, somatovegetative, vestibular syndroms. Taking into account thechanges in cortico-undercortical interrelations and expansion of pathologic process in hypothalamic area during the head trauma, we have developed effective treating methods by means of laseropuncture. Laser rays influence on acupuncture points (AP) leads to a convergence of the afferent messages upon the neurones of spinal cord, reticular formation, thalamus, hypothalamus and brain cortex.
As a result of that adynamic balance between the inhibition and excitation processes in the structures of central nervous system leading vegetative function and endocrine secretion recovers. Use of infrared laser radiation is the most perspective. It docs not cause the direct photochemical reactions in biological tissues, but influences on physico-chemical structure of AP biomolecules. For laseropuncture we used an apparatus with a wavelength of 0.89 nm. The work regime is impulsive-continuous with a modulation of frequency - from 0.1 to 1000 Hz. The middle power is up to 20 mW. The total time of the action for one sitting is till 20 min. The points selections was carried out on the grounds of the methods of acupuncture diagnosis, imagesking out the dominant clinical syndromes and including points of vascular, vegetotroimages, sedative orientation. Our clinical results, which were confirmed by paraclinical methods (EEG, dopplerography) and methods of acupuncture diagnosis have shown a high effectiveness of this therapy decreasing the drugs load and having no contradictions