We conclude that LLLT promotes proliferation and maturation of human osteoblasts in vitro. These results may have clinical implications.

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/cm 2 . 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. (Stroke. 2006; 37:2620-2624.)

Background-Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. Methods and Results-Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non-laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment (PϽ0.05) lowered mortality significantly, from 30% to 6.5%, after induction of MI. The infarct size in the LI dogs was reduced significantly (PϽ0.0001) (52%) compared with NLI dogs. Histological observation of the infarct revealed a typical scar tissue in NLI dogs and cellularity in most of the LI dogs. Only 14Ϯ3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36Ϯ1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats. Conclusions-Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI. Key Words: ischemia Ⅲ myocardial infarction Ⅲ antioxidants Ⅲ lasers T he approach to acute myocardial infarction (MI) has moved in the past decade from simple monitoring of coronary events to aggressive interventions in the processes underlying coronary thrombosis. Cardiac repair after infarct is a complex process involving diverse inflammatory components, extracellular matrix remodeling, and responses of the cardiomyocytes to the ischemia. 1,2 The sequential events that take place in the myocardium after occlusion of the left anterior descending coronary artery (LAD) in experimental animals (including dogs) have been well documented. 1,2 After necrosis of the cardiomyocytes and a rather long inflammatory phase, the ischemic zone is subsequently replaced by fibrotic tissue.Many studies have been directed toward the use of drugs, growth factors, and various interventional technologies in reducing myocardial infarct size and improvement of heart function after MI in experimental animals and humans. For example, recombinant adenovirus-mediated transfer of genes encoding antioxidants to the myocardium has been demonstrated to attenuate after ischemic dysfunction in neonatal mice. 3 Novel approaches to enhancing angiogenesis in the ischemic myocardium by introducing growth factors (mainly of the vascular endothelial growth factor family) were adapted and found to have a beneficial effect on patients with severe angina. 4 Low-energy laser irradiation (LELI) has b...

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.

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 Ͼ16 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 (Pϭ0.035 stratified by severity and time to treatment; Pϭ0.048 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 (Pϭ0.034 stratified by severity and time to treatment; Pϭ0.043 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 (Pϭ0.021 stratified by time to treatment) and the full mRS ("shift in Rankin") score (Pϭ0.020 stratified by severity and time to treatment; Pϭ0.026 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). Conclusion-The NE...

The present study clearly demonstrates the ability of LLLI to promote proliferation of MSCs and CSCs in vitro. These results may have an important impact on regenerative medicine.

It is concluded that VEGF and iNOS expression in the infarcted rat heart is markedly upregulated by LLLT and is associated with enhanced angiogenesis and cardioprotection.

Low-energy laser (He-Ne) irradiation was found to promote skeletal muscle regeneration in vivo. In this study, its effect on the proliferation and differentiation of satellite cells in vitro was evaluated. Primary rat satellite cells were irradiated for various time periods immediately after preparation, and thymidine incorporation was determined after 2 days in culture. Laser irradiation affected thymidine incorporation in a bell-shaped manner, with a peak at 3 s of irradiation. Three seconds of irradiation caused an induction of cell-cycle regulatory proteins: cyclin D1, cyclin E and cyclin A in an established line of mouse satellite cells, pmi28, and proliferating cell nuclear antigen (PCNA) in primary rat satellite cells. The induction of cyclins by laser irradiation was compatible with their induction by serum refeeding of the cells. Laser irradiation effect on cell proliferation was dependent on the rat's age. At 3 weeks of age, thymidine incorporation in the irradiated cells was more than twofold higher than that in the controls, while at 6 weeks of age this difference had almost disappeared. Myosin heavy chain (MHC) protein levels were twofold lower in the irradiated than in the control cells, whereas the proliferation of the irradiated cells was twofold higher. Fusion percentage was lower in the irradiated compared to non-irradiated cells. In light of these data, the promoting effect of laser irradiation on skeletal muscle regeneration in vivo may be due to its effect on the activation of early cell-cycle regulatory genes in satellite cells, leading to increased proliferation and to a delay in cell differentiation.