Effects of photobiomodulation on pain, lactate and muscle performance (ROM, torque, and EMG parameters) of paretic upper limb in patients with post-stroke spastic hemiparesis-a randomized controlled clinical trial.

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.

The effects of transcranial laser photobiomodulation and neuromuscular electrical stimulation in the treatment of post-stroke dysfunctions.

Post-stroke sequelae includes loss functions, such as cognitive and sensory-motor which lead to emotional and social problems, reducing quality of life and well-being. The main aim of our study was to investigate the effects of transcranial laser photobiomodulation together with neuromuscular electrical stimulation (NMES) in post-stroke patients. We performed a clinical trial and an ex vivo study. For the clinical trial, hemiplegic patients were separated into two groups: Treated Group (TG): Hemiplegics treated with transcranial laser (on) associated with NMES (on) and; Placebo Group (PG): Hemiplegics treated with placebo transcranial laser (off) associated with NMES (on). The cluster prototype includes 12 diode laser beams (4 × 660 nm, 4 × 808 nm and 4 × 980 nm) with average power of 720 mW per cluster applied during one minute, leading to 43.2 J energy per cluster. Fifteen regions for all head were irradiated by cluster, leading to 648 J energy per session. The parameters of NMES of the paretic limbs to generate extension wrist and ankle dorsiflexion were symmetrical biphasic rectangular waveforms, 50 Hz frequency, 250 µs pulse duration, and adjustable intensity to maintain the maximum range of motion (amplitude between 0 and 150 mA). Our clinical trial showed improvement of cognitive function, pain relief, greater manual dexterity, enhancement of physical and social-emotional health which lead to better quality of life and well-being. There was also increased temperature in the treated regions with laser and NMES. For the ex vivo study, the distribution of infrared and red radiation after penetration through the cranium and hemihead of cadavers were showed. Therefore, transcranial laser photobiomodulation associated with NMES can be an important therapeutic resource for rehabilitation after stroke.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Study of transcranial therapy 904 nm in experimental model of stroke.

Cerebrovascular accidents (CVAs), commonly known as strokes, can damage the brain through vascular injuries caused by either blood vessel blockages (ischemic stroke) or ruptures (hemorrhagic stroke) which disrupt regular brain blood supply and can cause severe damage to the individual. The objective of the present study was to evaluate the effects of photobiomodulation with a light-emitting diode (LED) device (904 nm, 110 mW, 7 J/cm2) on neurogenesis, muscle resistance, and motor behavior in animals submitted to an experimental model of hemiplegia. The sample consisted of 30 Wistar rats, divided into two groups: control group (GC) and 904-nm LED-treated group (TG). All animals underwent stereotactic surgery for electrode implant and subsequent electrolytic injury to induce an ischemic stroke. TG was subjected to daily LED irradiation (904 nm, 110 mW, 7 J/cm2) for 63 s. Suspension test results indicate an improvement of TG muscle resistance when compared with baseline evaluation (BLT); a reduction in open-field freezing time and the number of fecal bolus pellets suggest diminished anxiety induced by 904-nm LED treatment on treatment days 7 and 21 (TG7 and TG21) compared with the baseline results; and lastly, histological analysis showed important signs of neurogenesis in TG in comparison to CG, especially on treatment days 7 and 21 (TG7 and TG21). In conclusion, the present study suggests that 904-nm LED irradiation may beneficially affect neurogenesis, muscle resistance, and animal motor behavior following ischemic CVA.

Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.

Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.

Photobiomodulation for traumatic brain injury and stroke.

There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).

Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1ß and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression.

Transcranial Low-Level Laser (Light) Therapy for Brain Injury.

BACKGROUND: Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI). METHODS: 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. RESULTS: 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. CONCLUSIONS: Finally, some clinical studies in TBI patients are covered.

Effects of low-level laser therapy (LLLT 808 nm) on lower limb spastic muscle activity in chronic stroke patients.

A cerebrovascular accident (CVA) may affect basic motor functions, including spasticity that may be present in the upper extremity and/or the lower extremity, post-stroke. Spasticity causes pain, muscle force reduction, and decreases the time to onset of muscle fatigue. Several therapeutic resources have been employed to treat CVA to promote functional recovery. The clinical use of low-level laser therapy (LLLT) for rehabilitation of muscular disorders has provided better muscle responses. Thus, the aim of this study was to evaluate the effect of the application of LLLT in spastic muscles in patients with spasticity post-CVA. A double-blind clinical trial was conducted with 15 volunteer stroke patients who presented with post-stroke spasticity. Both males and females were treated; the average age was 51.5 ± 11.8 years old; the participants entered the study ranging from 11 to 48 months post-stroke onset. The patients participated in three consecutive phases (control, placebo, and real LLLT), in which all tests of isometric endurance of their hemiparetic lower limb were performed. LLLT (diode laser, 100 mW 808 nm, beam spot area 0.0314 cm(2), 127.39 J/cm(2)/point, 40 s) was applied before isometric endurance. After the real LLLT intervention, we observed significant reduction in the visual analogue scale for pain intensity (p = 0.0038), increased time to onset of muscle fatigue (p = 0.0063), and increased torque peak (p = 0.0076), but no significant change in the root mean square (RMS) value (electric signal in the motor unit during contraction, as obtained with surface electromyography). Our results suggest that the application of LLLT may contribute to increased recruitment of muscle fibers and, hence, to increase the onset time of the spastic muscle fatigue, reducing pain intensity in stroke patients with spasticity, as has been observed in healthy subjects and athletes.

Incremental treatments with laser therapy augments good behavioral outcome in the rabbit small clot embolic stroke model.

Transcranial near-infrared laser therapy (TLT) improves behavioral outcome in animal stroke models when applied as single treatment within the 24 h of the stroke onset. It is unknown if the multiple TLT treatments have an added beneficial effect. We aim to determine whether multiple irradiations with TLT would have further improvement in behavioral outcomes in the rabbit small clot embolic stroke model (RSCEM). Using the RSCEM, two and three TLT treatments (7.5-20 mW/cm(2)) were compared against single laser treatment alone (7.5-10.8 mW/cm(2)). Two sham irradiation groups were added for the control curves. The double treatment group received TLT at 3 and 5 h and the triple treatment group at 2, 3, and 4 h after embolization. Behavioral analysis was conducted 24 h after embolization using a dichotomized behavioral score. The determination of the effective clot amount (milligrams) that produces neurological deficits in 50 % of the rabbits (P 50) was used to compare TLT treatments with the sham. The P 50 for double treatment was 5.47 ± 0.90, with n = 39; the corresponding P 50 value for a single treatment was 3.87 ± 0.73, with n = 38; and the corresponding control curve was 3.25 ± 0.4, n = 32. The P 50 for triple treatment was 5.91 ± 0.49, with n = 23; the corresponding P 50 value for a single treatment was 3.09 ± 0.59, with n = 15, and the corresponding control curve was 1.71 ± 0.26, with n = 17. The triple treatment had 91 % improvement when compared with the single treatment and 245 % improvement when compared with the sham. The present study suggests that the additional TLT treatments provide further behavioral improvement when given during the acute ischemic stroke phase.

Transcranial low level laser (light) therapy for traumatic brain injury.

We review the use of transcranial low-level laser (light) therapy (LLLT) as a possible treatment for traumatic-brain injury (TBI). The basic mechanisms of LLLT at the cellular and molecular level and its effects on the brain are outlined. Many interacting processes may contribute to the beneficial effects in TBI including neuroprotection, reduction of inflammation and stimulation of neurogenesis. Animal studies and clinical trials of transcranial-LLLT for ischemic stroke are summarized. Several laboratories have shown that LLLT is effective in increasing neurological performance and memory and learning in mouse models of TBI. There have been case report papers that show beneficial effects of transcranial-LLLT in a total of three patients with chronic TBI. Our laboratory has conducted three studies on LLLT and TBI in mice. One looked at pulsed-vs-continuous wave laser-irradiation and found 10 Hz to be superior. The second looked at four different laser-wavelengths (660, 730, 810, and 980 nm); only 660 and 810 nm were effective. The last looked at different treatment repetition regimens (1, 3 and 14-daily laser-treatments).

Effectiveness and safety of transcranial laser therapy for acute ischemic stroke.

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.

Laser therapy in acute stroke treatment.

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.

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.

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.

Laser treatment for stroke.

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.

Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1).

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.

[Effect of magnet-laser therapy on the central nervous system functional state in patients with ischemic stroke].

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.

Low-level laser therapy applied transcranially to rats after induction of stroke significantly reduces long-term neurological deficits.

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.

Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke.

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.

Transcranial infrared laser therapy improves clinical rating scores after embolic strokes in rabbits.

BACKGROUND AND PURPOSE: Because photon energy delivered using a low-energy infrared laser may be useful to treat stroke, we determined whether transcranial laser therapy would improve behavioral deficits in a rabbit small clot embolic stroke model (RSCEM). METHODS: In this study, the behavioral and physiological effects of laser treatment were measured. The RSCEM was used to assess whether low-energy laser treatment (7.5 or 25 mW/cm2) altered clinical rating scores (behavior) when given to rabbits beginning 1 to 24 hours postembolization. Behavioral analysis was conducted from 24 hours to 21 days after embolization, 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. RESULTS: In the present study, the P50 value for controls were 0.97+/-0.19 mg to 1.10+/-0.17 mg; this was increased by 100% to 195% (P50=2.02+/-0.46 to 2.98+/-0.65 mg) if laser treatment was initiated up to 6 hours, but not 24 hours, postembolization (P50=1.23+/-0.15 mg). Laser treatment also produced a durable effect that was measurable 21 days after embolization. Laser treatment (25 mW/cm2) did not affect the physiological variables that were measured. CONCLUSIONS: This study shows that laser treatment improved behavioral performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable. Therefore, transcranial laser treatment may be useful to treat human stroke patients and should be further developed.