Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.
- 11 VA Boston Healthcare System (12-A) , Boston, Massachusetts.
- 22 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.
- 33 Department of Psychiatry, Boston University School of Medicine , Boston, Massachusetts.
- 44 Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts.
- 55 Department of Physical Medicine and Rehabilitation, Harvard Medical School , Boston, Massachusetts.
- 66 Spaulding Rehabilitation Hospital , Charlestown, Massachusetts.
- 77 Massachusetts General Hospital , Boston, Massachusetts.
- 88 Brigham and Women’s Hospital , Boston, Massachusetts.
- 99 TBI Research Program, Spaulding Rehabilitation Hospital , Charlestown, Massachusetts.
- 1010 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston Massachusetts.
- 1111 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.
- 1212 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.
- 1313 Boston University Center for Biomedical Imaging , Boston, Massachusetts.
We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35?cm diameter, 500?mW, 22.2?mW/cm2) was applied for 9?min 45?sec (13?J/cm2) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26?J/cm2 per LED location on the head or treated with intranasal only (iLED) using red (633?nm) and NIR (810?nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633?nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.
Transcranial Low-Level Laser (Light) Therapy for Brain Injury.
- 11 Harvard College , Cambridge, Massachusetts.
- 22 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts.
- 33 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.
- 44 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.
Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI).
We review the fundamental mechanisms at the cellular and molecular level and the effects on the brain are discussed. There are several contributing processes that have been proposed to lead to the beneficial effects of PBM in treating TBI such as stimulation of neurogenesis, a decrease in inflammation, and neuroprotection. Both animal and clinical trials for ischemic stroke are outlined. A number of articles have shown how transcranial LLLT (tLLLT) is effective at increasing memory, learning, and the overall neurological performance in rodent models with TBI.
Our laboratory has conducted three different studies on the effects of tLLLT on mice with TBI. The first studied pulsed against continuous laser irradiation, finding that 10?Hz pulsed was the best. The second compared four different wavelengths, discovering only 660 and 810?nm to have any effectiveness, whereas 732 and 980?nm did not. The third looked at varying regimens of daily laser treatments (1, 3, and 14 days) and found that 14 laser applications was excessive. We also review several studies of the effects of tLLLT on neuroprogenitor cells, brain-derived neurotrophic factor and synaptogenesis, immediate early response knockout mice, and tLLLT in combination therapy with metabolic inhibitors.
Finally, some clinical studies in TBI patients are covered.
The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women.
1Institute of Biomedical Engineering, Camilo Castelo Branco University, Unicastelo, S J dos Campos, São Paulo, 12247-004, Brazil, firstname.lastname@example.org.
During aging processes, there is a range of functional changes, where we can highlight the disease related to the central nervous system, such as Alzheimer disease and others forms of dementia. This study investigated the effects of transcranial light emitting diode (LED) on cerebral blood flow in healthy elderly women analyzed by transcranial Doppler ultrasound (TCD) of the right and left middle cerebral artery and basilar artery. Twenty-five noninstitutionalized elderly women (mean age 72 years old), with a cognitive status >24, were assessed using transcranial Doppler ultrasound on two separate occasions: pre-irradiation and post-transcranial LED therapy (TCLT). Prior to this, they answered two questionnaires: the perceived stress scale and the general health questionnaire. TCLT (627 nm, 70 mW/cm(2), 10 J/cm(2)) was performed at four points of the frontal and parietal region for 30 s each, totaling 120 s two times per week for 4 weeks. Paired t-test results showed that there was a significant improvement after TCLT with increase in the systolic and diastolic velocity of the left middle cerebral artery (25 and 30%, respectively) and basilar artery (up to 17 and 25%), as well as a decrease in the pulsatility index and resistance index values of the three cerebral arteries analyzed (p<0.05). TCD parameters showed improvement in the blood flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women.
Low-level laser therapy effectively prevents secondary brain injury induced by immediate early responsive gene X-1 deficiency.
A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1? and IL-6 but upregulated TNF-?. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.Journal of Cerebral Blood Flow & Metabolism advance online publication, 21 May
Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice.
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
BACKGROUND AND OBJECTIVE:
Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI.
STUDY DESIGN/MATERIALS AND METHODS:
TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test.
The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests.
The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.
J Neurotrauma. 2011 Sep 21. [Epub ahead of print]
Low-Level Laser Light Therapy Improves Cognitive Deficits and Inhibits Microglial Activation after Controlled Cortical Impact in Mice.
1 Neuroscience Center, Massachusetts General Hospital , Harvard Medical School, Charlestown, Massachusetts.
Abstract 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 (800?nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80?min after CCI. Injured mice treated with 60?J/cm(2) (500?mW/cm(2)×2?min) 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 48?h (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 60?J/cm(2). No effect of LLLT (60?J/cm(2) open craniotomy) was observed on post-injury motor function (days 1-7), brain edema (24?h), nitrosative stress (24?h), 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.
J Neurotrauma. 2011 Aug 18. [Epub ahead of print]
Low-Level Laser Light Therapy Improves Cognitive Deficits and Inhibits Microglial Activation after Controlled Cortical Impact in Mice.
Massachusetts General Hospital , Neuroscience Center and Department of Pediatrics, 149 Thirteenth street, Charlestown, Massachusetts, United States, 02129; email@example.com.
Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcome after experimental TBI (Oron et al., 2007), and coherent near infrared light has been reported to improve cognitive function in patients with chronic TBI (Naeser et al., 2010). However, effects of LLLT on cognitive recovery in experimental TBI are lacking. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve postinjury Morris water maze performance. Low-level laser light (800 nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80 min after CCI. Injured mice treated with 60 J/cm2 (500 mW/cm2 x 2 min) 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 vs. 39.2 + 4.2 IbA-1+ cells/x200 field, p < 0.05). Little or no effect of LLLT on postinjury cognitive function was observed using other doses, a 4 h administration time point and 7 day administration of 60 J/cm2. No effect of LLLT (60 J/cm2 open craniotomy) was observed on postinjury motor function (d 1-7), brain edema (24 h), nitrosative stress (24 h), or lesion volume (14 d). 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.
Photomed Laser Surg. 2010 Dec 23. [Epub ahead of print]
Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports.
Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA.
1 VA Boston Healthcare System , Boston, Massachusetts.
Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented.
Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1? diameter, 61 diodes (9?×?633?nm, 52?×?870?nm); 12-15?mW per diode; total power: 500?mW; 22.2?mW/cm(2); 13.3?J/cm(2) at scalp (estimated 0.4?J/cm(2) to cortex)].
Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment.
Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.
Brain Res. 2010 Jan 8;1306:100-5. Epub 2009 Oct 23.
Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5′-triphosphate (ATP) content following embolic strokes in rabbits.
Lapchak PA, De Taboada L.
University of California San Diego, Department of Neuroscience, 9500 Gilman Drive MTF316, La Jolla, CA 92093-0624, USA. firstname.lastname@example.org
- Brain Res. 2010 Mar 19;1321:182.
Transcranial near infrared laser therapy (NILT) improves behavioral outcome following embolic strokes in embolized rabbits and clinical rating scores in acute ischemic stroke (AIS) patients; however, the cellular mechanism(s) involved in NILT neuroprotection have not been elucidated. It has been proposed that mitochondrial energy production may underlie a response to NILT, but this has not been demonstrated using an in vivo embolic stroke model. Thus, we evaluated the effect of NILT on cortical ATP content using the rabbit small clot embolic stroke model (RSCEM), the model originally used to demonstrate NILT efficacy and initiate the NEST-1 clinical trial. Five minutes following embolization, rabbits were exposed to 2 min of NILT using an 808 nm laser source, which was driven to output either continuous wave (CW), or pulsed wave modes (PW). Three hours after embolization, the cerebral cortex was excised and processed for the measurement of ATP content using a standard luciferin-luciferase assay. NILT-treated rabbits were directly compared to sham-treated embolized rabbits and naïve control rabbits. Embolization decreased cortical ATP content in ischemic cortex by 45% compared to naive rabbits, a decrease that was attenuated by CW NILT which resulted in a 41% increase in cortical ATP content compared to the sham embolized group (p>0.05). The absolute increase in ATP content was 22.5% compared to naive rabbits. Following PW NILT, which delivered 5 (PW1) and 35 (PW2) times more energy than CW, we measured a 157% (PW1 p=0.0032) and 221% (PW2 p=0.0001) increase in cortical ATP content, respectively, compared to the sham embolized group. That represented a 41% and 77% increase in ATP content compared to naive control rabbits. This is the first demonstration that embolization can decrease ATP content in rabbit cortex and that NILT significantly increases cortical ATP content in embolized rabbits, an effect that is correlated with cortical fluence and the mode of NILT delivery. The data provide new insight into the molecular mechanisms associated with clinical improvement following NILT.
Stroke. 2009 Published online before print February 20, 2009, doi: 10.1161/STROKEAHA.109.547547
Submitted on January 12, 2009
Revised on January 26, 2009
Accepted on January 27, 2009
Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke
Justin A. Zivin MD, PhD*; Gregory W. Albers MD; Natan Bornstein MD; Thomas Chippendale MD, PhD; Bjorn Dahlof MD, PhD; Thomas Devlin MD, PhD; Marc Fisher MD; Werner Hacke MD, PhD; William Holt DO; Sanja Ilic MD; Scott Kasner MD; Robert Lew PhD; Marshall Nash MD; Julio Perez MD; Marilyn Rymer MD; Peter Schellinger MD, PhD; Dietmar Schneider MD; Stefan Schwab MD; Roland Veltkamp MD; Michael Walker PhD; Jackson Streeter MD; for the NEST-2 Investigators
From the Department of Neurosciences (J.Z.), University of California San Diego, La Jolla, Calif; Stanford Stroke Center (G.A.), Stanford University Medical Center, Palo Alto, Calif; Tel Aviv Medical Center (N.B.), Tel Aviv, Israel; Scripps Hospital (T.C.), Encinitas, Calif; Sahlgrenska University Hospital (B.D.), Gothenburg, Sweden; Erlanger Health System (T.D.), Chattanooga, Tenn; University of Massachusetts Medical School (M.F.), Worcester, Mass; Department of Neurology (W.H.), Universität Heidelberg, Heidelberg, Germany; Fawcett Memorial Hospital (W.A.H.), Port Charlotte, Fla; Triage Wireless, Inc (S.I.), San Diego, Calif; the Department of Neurology (S.E.K.), University of Pennsylvania School of Medicine, Philadelphia, Pa; Boston University (R.L.), Boston, Mass; DeKalb Neurology Associates (M.N.), Decatur, Ga; Hospital Nacional Dos de Mayo (J.P.), Lima, Peru; St. Luke’s Health System (M.R.), Kansas City, Mo; Universitätsklinikum Erlangen (P.S.), Erlangen, Germany; the Department of Neurology (D.S.), Universität Leipzig, Leipzig, Germany; Universitätsklinikum Erlangen (S.S.), Erlangen, Germany; Department of Neurology (R.V.), Universität Heidelberg, Heidelberg, Germany; Stanford Center for Biomedical Informatics Research (M.W.), Stanford School of Medicine, Palo Alto, Calif; and PhotoThera, Inc (J.S.), Carlsbad, Calif.
* To whom correspondence should be addressed. E-mail: email@example.com.
Background and Purpose—We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial–2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke.
Methods—This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score.
Results—We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P=0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of <16 showed a favorable outcome at 90 days on the primary end point (P<0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively.
Conclusions—TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned.
J Photochem Photobiol B.J Photochem Photobiol B. 2009 Dec 2;97(3):145-51. Epub 2009 Sep 11.
Effect of phototherapy with low intensity laser on local and systemic immodulation following focal brain damage in rat.
Moreira MS, Velasco IT, Ferreira LS, Ariga SK, Barbeiro DF, Meneguzzo DT, Abatepaulo F, Marques MM.LIM-51, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over therapeutic management for these patients. The objective of this study was to analyze the effect of phototherapy with low intensity lasers on local and systemic immunomodulation following cryogenic brain injury. Laser phototherapy was applied (or not-controls) immediately after cryogenic brain injury performed in 51 adult male Wistar rats. The animals were irradiated twice (3 h interval), with continuous diode laser (gallium-aluminum-arsenide (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP), 660 nm) in two points and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). The experimental groups were: Control (non-irradiated), RL3 (visible red laser/ 3 J/cm(2)), RL5 (visible red laser/5 J/cm(2)), IRL3 (infrared laser/3 J/cm(2)), IRL5 (infrared laser/5 J/cm(2)). The production of interleukin-1IL-1beta (IL-1beta), interleukin6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme immunoassay technique (ELISA) test in brain and blood samples. The IL-1beta concentration in brain of the control group was significantly reduced in 24 h (p<0.01). This reduction was also observed in the RL5 and IRL3 groups. The TNF-alpha and IL-6 concentrations increased significantly (p<0.01 and p<0.05, respectively) in the blood of all groups, except by the IRL3 group. The IL-6 levels in RL3 group were significantly smaller than in control group in both experimental times. IL-10 concentration was maintained stable in all groups in brain and blood. Under the conditions of this study, it is possible to conclude that the laser phototherapy can affect TNF-alpha, IL-1beta and IL-6 levels in the brain and in circulation in the first 24 h following cryogenic brain injury.
Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):3-11.
Many-level polysensory stimulation of brain functions by physical therapeutic agents.
[Article in Russian]
Tyshkevich TG, Ponomarenko GN.
A combination of physiotherapeutic methods for neurorehabilitative treatment has been developed and applied to the treatment of 576 patients with neurosurgical problems including the loss of brain functions as a sequel to nervous system lesions of traumatic, vascular, and other origin. Methodologically, this complex is adapted to the level and extent of the lesion and the character of regeneration of the nervous tissues. It implies many-level stimulation of neuroregeneration by syndromically and pathogenetically substantiated application of physical factors in the early post-injury and postoperative periods. The proposed approach allows the brain function to be completely restored by virtue of persistent compensatory changes in the nervous system. A combination of many-level magnetic, electrical, and laser stimulation is recommended to manage lesions in the speech, motor, and visual analyzers. Combined laser and differential electrostimulation may be prescribed to patients with nerve lesions, extremely high frequency therapy to those with epileptic syndrome, combined microwave therapy to cases with impairment of consciousness, and a variant of systemic UV irradiation with underwater shower-massaging for the treatment of vegetative and asthenic disturbances. Selected physiological aspects of the action of the above physical factors are specified. This physiotherapeutic system is protected by 20 RF patents of invention.
Stroke. 2008 Nov;39(11):3073-8. Epub 2008 Aug 7.
Safety profile of transcranial near-infrared laser therapy administered in combination with thrombolytic therapy to embolized rabbits.
Lapchak PA, Han MK, Salgado KF, Streeter J, Zivin JA.
Department of Neuroscience, University of California San Diego, La Jolla, CA 92093-0624, USA. firstname.lastname@example.org
BACKGROUND AND PURPOSE: Transcranial near-infrared laser therapy (TLT) is currently under investigation in a pivotal clinical trial that excludes thrombolytic therapy. To determine if combining tissue plasminogen activator (tPA; Alteplase) and TLT is safe, this study assessed the safety profile of TLT administered alone and in combination with Alteplase. The purpose for this study is to determine if the combination of TLT and thrombolysis should be investigated further in a human clinical trial.
METHODS: We determined whether postembolization treatment with TLT in the absence or presence of tPA would affect measures of hemorrhage or survival after large clot embolism-induced strokes in New Zealand white rabbits.
RESULTS: TLT did not significantly alter hemorrhage incidence after embolization, but there was a trend for a modest reduction of hemorrhage volume (by 65%) in the TLT-treated group compared with controls. Intravenous administration of tPA, using an optimized dosing regimen, significantly increased hemorrhage incidence by 160%. The tPA-induced increase in hemorrhage incidence was not significantly affected by TLT, although there was a 30% decrease in hemorrhage incidence in combination-treated rabbits. There was no effect of TLT on hemorrhage volume measured in tPA-treated rabbits and no effect of any treatment on 24-hour survival rate.
CONCLUSIONS: In the embolism model, TLT administration did not affect the tPA-induced increase in hemorrhage incidence. TLT may be administered safely either alone or in combination with tPA because neither treatment affected hemorrhage incidence or volume. Our results support the study of TLT in combination with Alteplase in patients with stroke.
Int J Stroke. 2008 May;3(2):88-91.
Laser therapy in acute stroke treatment.
Yip S, Zivin J.
Department of Neuroscience, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA.
Recent development of near infrared light therapy (NILT) as an acute stroke treatment is promising. In various preclinical animal stroke models, NILT has been shown to be effective in improving long-term stroke outcome. More importantly, NILT has a long postischemic therapeutic window that has not been previously observed in other treatment modalities. The preliminary efficacy and safety of NILT in acute stroke patients were demonstrated in the recently published phase II NeuroThera Effectiveness and Safety Trial (NEST-1). If confirmed by the NEST-II trial, NILT will revolutionize acute stroke management as ut has a long time window (possible 24 hr) for therapy. Moreover, understanding the mechanisms of action of NILT will provide a new therapeutic target for future drug or device development.
Neuroscience. 2007 Sep 21;148(4):907-14. Epub 2007 Jul 12
Transcranial near-infrared light therapy improves motor function following embolic strokes in rabbits: an extended therapeutic window study using continuous and pulse frequency delivery modes.
Lapchak PA, Salgado KF, Chao CH, Zivin JA.
University of California San Diego, Department of Neuroscience, MTF 316, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA. email@example.com
Photon or near-infrared light therapy (NILT) may be an effective neuroprotective method to reduce behavioral dysfunction following an acute ischemic stroke. We evaluated the effects of continuous wave (CW) or pulse wave (P) NILT administered transcranially either 6 or 12 h following embolization, on behavioral outcome. For the studies, we used the rabbit small clot embolic stroke model (RSCEM) using three different treatment regimens: 1) CW power density of 7.5 mW/cm(2); 2) P1 using a frequency of 300 mus pulse at 1 kHz or 3) P2 using a frequency of 2 ms pulse at 100 Hz. Behavioral analysis was conducted 48 h after embolization, allowing for the determination of the effective stroke dose (P(50)) 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 P(50) compared with the control group. Quantal dose-response analysis showed that the control group P(50) value was 1.01+/-0.25 mg (n=31). NILT initiated 6 h following embolization resulted in the following P(50) values: (CW) 2.06+/-0.59 mg (n=29, P=0.099); (P1) 1.89+/-0.29 mg (n=25, P=0.0248) and (P2) 1.92+/-0.15 mg (n=33, P=0.0024). NILT started 12 h following embolization resulted in the following P(50) values: (CW) 2.89+/-1.76 mg (n=29, P=0.279); (P1) 2.40+/-0.99 mg (n=24, P=0.134). At the 6-h post-embolization treatment time, there was a statistically significant increase in P(50) values compared with control for both pulse P1 and P2 modes, but not the CW mode. At the 12-h post-embolization treatment time, neither the CW nor the P1 regimens resulted in statistically significant effect, although there was a trend for an improvement. The results show that P mode NILT can result in significant clinical improvement when administered 6 h following embolic strokes in rabbits and should be considered for clinical development.
Expert Rev Neurother.2007 Aug;7(8):961-5.
Laser treatment for stroke.
Edith Wolfson Medical Center, Department of Neurology, Holon, Israel. firstname.lastname@example.org
Low-level laser therapy is an irradiation technique that has the ability to induce biological processes using photon energy. There are studies showing proliferation and angiogenesis after irradiation in skeletal muscle post-myocardial infarction tissue cells. Most evidence of efficacy is based on the increase in energy state and the activation of mitochondrial pathways. In the brain, there is similar evidence of cellular activity with laser irradiation. In vivo studies reinforced the efficacy of this technique for a better neurological and functional outcome post-stroke. The evidence is based on in vivo animal studies of various models and one human clinical study. Although the data is very promising, some fundamental questions remain to be answered, such as the exact mechanism along the cascade of post-stroke interconnective molecular disturbance, the optimal technique and time of treatment, and the long-term safety aspects. The answers to these questions are expected to evolve within the next few years.
Stroke. 2007 Jun;38(6):1843-9. Epub 2007 Apr 26.
Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1).
Lampl Y, Zivin JA, Fisher M, Lew R, Welin L, Dahlof B, Borenstein P, Andersson B, Perez J, Caparo C, Ilic S, Oron U.
Wolfson Medical Center, Department of Neurology, Holon, Israel.
BACKGROUND AND PURPOSE: The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke.
METHODS: This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients’ scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment. The primary outcome measure, prospectively identified, was successful treatment, documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline), and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results.
RESULTS: Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS (“shift in Rankin”) score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs).
CONCLUSIONS: The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.
J Neurotrauma. 2007 Apr;24(4):651-6.
Low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits.
Oron A, Oron U, Streeter J, de Taboada L, Alexandrovich A, Trembovler V, Shohami E.
Department of Orthopedics, Assaf Harofeh Medical Center, Zerifin, Israel. email@example.com
Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. TBI was induced by a weight-drop device, and motor function was assessed 1 h post-trauma using a neurological severity score (NSS). Mice were then divided into three groups of eight mice each: one control group that received a sham LLLT procedure and was not irradiated; and two groups that received LLLT at two different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser was employed transcranially 4 h post-trauma to illuminate the entire cortex of the brain. Motor function was assessed up to 4 weeks, and lesion volume was measured. There were no significant changes in NSS at 24 and 48 h between the laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS of the laser-treated mice were significantly lower (p < 0.05) than the traumatized control mice that were not treated with the laser. The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.
Stroke. 2006 Oct;37(10):2620-4. Epub 2006 Aug 31
Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.
Oron A, Oron U, Chen J, Eilam A, Zhang C, Sadeh M, Lampl Y, Streeter J, DeTaboada L, Chopp M.
Department of Orthopedics, Assaf Harofeh Medical Center, Zerifin 70300, Israel. firstname.lastname@example.org
BACKGROUND AND PURPOSE: Low-level laser therapy (LLLT) modulates various biological processes. In the present study, we assessed the hypothesis that LLLT after induction of stroke may have a beneficial effect on ischemic brain tissue.
METHODS: Two sets of experiments were performed. Stroke was induced in rats by (1) permanent occlusion of the middle cerebral artery through a craniotomy or (2) insertion of a filament. After induction of stroke, a battery of neurological and functional tests (neurological score, adhesive removal) was performed. Four and 24 hours poststroke, a Ga-As diode laser was used transcranially to illuminate the hemisphere contralateral to the stroke at a power density of 7.5 mW/cm2.
RESULTS: In both models of stroke, LLLT significantly reduced neurological deficits when applied 24 hours poststroke. Application of the laser at 4 hours poststroke did not affect the neurological outcome of the stroke-induced rats as compared with controls. There was no statistically significant difference in the stroke lesion area between control and laser-irradiated rats. The number of newly formed neuronal cells, assessed by double immunoreactivity to bromodeoxyuridine and tubulin isotype III as well as migrating cells (doublecortin immunoactivity), was significantly elevated in the subventricular zone of the hemisphere ipsilateral to the induction of stroke when treated by LLLT.
CONCLUSIONS: Our data suggest that a noninvasive intervention of LLLT issued 24 hours after acute stroke may provide a significant functional benefit with an underlying mechanism possibly being induction of neurogenesis.
Photomed Laser Surg. 2006 Aug;24(4):458-66
Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain.
Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U.
Photothera Inc., Carlsbad, California, USA.
OBJECTIVE: The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain.
BACKGROUND DATA: LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available.
METHODS: One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the follow-up periods after laser irradiation. Histology was performed at light and electron microscopy levels.
RESULTS: Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted.
CONCLUSION: Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.
Lasers Surg Med. 2006 Jan;38(1):70-3
Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke.
Detaboada L, Ilic S, Leichliter-Martha S, Oron U, Oron A, Streeter J.
Photothera, Inc., 2260 Rutherford Road, Carlsbad, California 92008, USA.
BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the present study was to approve the effectiveness of LLLT treatment at different locations on the brain in acute stroked rats.
STUDY DESIGN/MATERIALS AND METHODS: Stroke was induced in 169 rats that were divided into four groups: control non-laser and three laser-treated groups where laser was employed ipsilateral, contralateral, and both to the side of the induced stroke. Rats were tested for neurological function. RESULTS: In all three laser-treated groups, a marked and significant improvement in neurological deficits was evident at 14, 21, and 28 days post stroke relative to the non-treated group. CONCLUSIONS: These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.
Progress in Laser Therapy
This paper appears in: Lasers and Electro-Optics Society, 2006. LEOS 2006. 19th Annual Meeting of the IEEE
The presentation covers fundamental operating principles of some of the most widely used methods of low-level laser therapy (LLLT). It includes also recently developed LLLT technologies and medical devices such as LLLT cardiovascular and brain therapy, tissue regeneration and pain relive. The mechanism of LLLT involving interaction with mitochondria. The effects of LLLT are wavelength specific upon a known mitochondrial receptor (cytochrome C oxidase). Targeting of this receptor results in formation of adenosine triphosphate (ATP), enhanced mitochondrial survival and maintenance of cytochrome C oxidase activity
Lik Sprava. 2006 Apr-May;(3):51-4.
Effect of magnet-laser therapy on the central nervous system functional state in patients with ischemic stroke.
[Article in Russian]
Twenty three patients aged from 41 to 75, which have had ischemic stroke in the carotid basin (up to 2 years after an acute period of the stroke), have been examined. The course of magneto-laser therapy lasted 15 days. The author carried out neurological examinations, determined the state of psychoemotional activity, cerebral hemodynamics and frequency-amplitude indices of the brain to assess the mechanisms of MLT effect on the CNS functional state in patients being in a rehabilitative period after ischemic stroke. The course of MLT administration improves cerebral hemodynamics, increases the level of the bioelectrical activity of the brain. We can recommend based on obtained results MLT in the system of rehabilitation of patients which had had ischemic stroke.
|Zhong Xi Yi Jie He Xue Bao. 2005 Mar;3(2):128-31.|
Protective effect of low-level irradiation on acupuncture points combined with iontophoresis against focal cerebral ischemia-reperfusion injury in rats.
[Article in Chinese]
Dai JY, Ge LB, Zhou YL, Wang L.
Acupuncture Clinic, Institute of Qigong, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China. email@example.com
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 electro-acupuncture 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.
ACTA LASER BIOLOGY SINICA Vol. 8, No.2, 1999
Vascular Low Level Laser Irradiation Therapy in Treatment of Brain Injury
WANG Yu ZHU Jing, et al
(Department of Neurosurgery, Renji Hospital Affiliated to Shanghai Second Medical University, Shanghai Medical Centre for laser Research ,200001)
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.
INFRARED LASER RADIATION IN THE TREATMENT OF BRAIN INJURY CONSEQUENCES
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, somato-vegetative, vestibular syndroms. Taking into account the changes 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 a dynamic 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 “BIOMED-01” 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.
LASER-THERAPY AND ITS INFLUENCE ON HEMODYNAMICS WITH PATIENTS SUFFERED FROM GRAVE CRANIOCEREBRAL TRAUMA
Medical Academy, Dnepropetrovsk, Ukraine
Despite the maximal dosage of different medications taken for curing of grave craniocerebral trauma the resistance to the treatment carried out was observed. This fact stimulated the search of new methods and ways of therapy. One of the possible methods is a non-medicamental treatment based on blood irradiation with low-active helium-neon laser. The present paper presents some data concerning the laser-therapy influence in hemodynamics in the case of craniocerebral trauma. The total number of patients examined is 45. Laser-therapy was carried out through the subclavian vein (37 cases) or cubital vein (8 cases). For primary irradiation the preferable access was the central one. It was used in the acute period of craniocerebral trauma. The periferal access was used for irradiation in the posthospital period. The course of laser therapy for in-hospital patients consisted of 3-5 everyday procedures of 30 minutes each. To define the hemodynamic changes with the patients suffered from craniocerebral trauma both clinical observation and ultrasonic transcranial dopplerography were used. The last one gave the possibility to identify the type of blood flow speed disorders.
Specific Effects of Laserpuncture on the Cerebral Circulation
G. Litscher (1), L. Wang (1), M. Wiesner-Zechmeister (2)(1) Biomedical Engineering, Department of Anesthesiology and Critical Care, University of Graz, Graz, Austria(2) European Forum for Lasertherapy and Fractal Medicine
Paper received 10 May 1999; accepted after revision 23 August 1999.
Abstract . Acupuncture is a form of traditional Chinese medicine that has developed over thousands of years. We studied the effects of laser puncture, needle acupuncture, and light stimulation on cerebral blood flow in 15 healthy volunteers (mean age 25.0±1.9 years, 5 female, 10 male) with non-invasive transcranial Doppler sonography. In addition 40-Hz stimulus-induced brain oscillations, heart rate, blood pressure, peripheral and cerebral oxygen saturation, and the bispectral index of the EEG were recorded. Stimulation with light significantly increased blood flow velocity in the posterior cerebral artery (p<0.01, ANOVA). Similar but less pronounced effects were seen after needle acupuncture (p< 0.05, ANOVA) and laserpuncture (n.s.) of vision-related acupuncture points. Furthermore both, laserpuncture and needle acupuncture, led to a significant increase in the amplitudes of 40-Hz cerebral oscillations. Stimulation of vision-related acupuncture points with laser light or needle acupuncture elicits specific effects in specific areas of the brain. The results indicate that the brain plays a key intermediate role in acupuncture. However, brain activity of itself does not explain anything about the healing power of acupuncture.