Article

Effect of near-infrared light-emitting diodes on nerve regeneration

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Abstract

Photobiomodulation by red to near-infrared light-emitting diodes (LEDs) has been reported to accelerate wound healing, attenuate degeneration of an injured optic nerve, and promote tissue growth. The purpose of this study was to investigate the effect of LEDs on nerve regeneration. A histological study as well as a measurement of antioxidation levels in the nerve regeneration chamber fluid was performed. For the histological study, the bilateral sciatic nerves were transected, and the left proximal stump and the right distal stump were inserted into the opposite ends of a silicone chamber, leaving a 10-mm gap. Light from an LED device (660 nm, 7.5 mW/cm(2)) was irradiated for 1 h per day. At 3 weeks after surgery, regenerated tissue was fixed and examined by light microscopy. For the antioxidation assay of chamber fluid, the left sciatic nerve and a 2-mm piece of nerve from the proximal stump were transected and inserted into opposite sides of a silicone chamber leaving a 10-mm gap. LEDs were irradiated using the same parameters as those described in the histological study. At 1, 3, and 7 days after surgery, antioxidation of the chamber fluid was measured using an OXY absorbent test. Nerve regeneration was promoted in the LED group. Antioxidation of the chamber fluid significantly decreased from 3 days to 7 days in the control group. In the LED group, antioxidation levels did not decrease until 7 days. Chamber fluid is produced from nerve stumps after nerve injury. This fluid contains neurotrophic factors that may accelerate axonal growth. Red to near-infrared LEDs have been shown to promote mitochondrial oxidative metabolism. In this study, LED irradiation improved nerve regeneration and increased antioxidation levels in the chamber fluid. Therefore, we propose that antioxidation induced by LEDs may be conducive to nerve regeneration.

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... Both positive and null effects of the use of LED irradiation on morphofunctional recovery following a nerve injury have been described. The reported positive effects are a reduction in inflammatory cells, reduction in edema, accelerated wound healing, a greater number of myelinated axons, larger endoneural area, accelerated axon growth, and accelerated growth of neurites in the dorsal ganglia (6,20,21). The reported null effects are the nonacceleration of nerve regeneration, nonreduction in cold hypersensitivity, nonalteration of IL-1b levels, nonacceleration of muscle recovery, nonimprovement of myelinated fiber density, and nonincrease in the myelin sheath and myelinated fiber area (22,23). ...
... The effects of PBMT on nerve regeneration include increases in growth, axonal diameter, myelinization, and the number of Schwann cells as well as a reduction in mononuclear inflammatory infiltrate, the promotion of extracellular matrix remodeling, functional improvement, an increase in the expression of neurotrophic growth factors and assistance in the control of oxidation in injured tissues (19,20,(30)(31)(32)(33). ...
... In a model of sciatic neurotmesis on Wistar rats (with 10 mm gap and tubulization), LED therapy (660 nm, 27 J cm À2 and 7.5 mW cm À2 ) promoted greater nerve and endoneurial areas in addition to a greater number of axons compared to the control group. LED was applied one hour per day for three weeks using a panel-shaped device (30 9 30 cm) (20). ...
Article
Peripheral injuries constitute a substantial clinical problem with unsatisfactory treatment. The study’s objective was to analyze the effects of Photobiomodulation therapy (PBMT) on median nerve regeneration and muscle recovery after axonotmesis. Twenty‐four rats were randomized into three groups: control (CG), injury (IG) and LED therapy (LEDG). A 630 ± 20 nm (300‐mW) LED was placed in contact with the skin. One point over the injury site was irradiated for 30 s, delivering 9 J (9 J/cm2). PBMT irradiation was performed once daily for 5 days followed by two‐day interval and then more 5 consecutive days of treatment. Proximal and distal segments of the nerve and flexors muscles were removed for histomorphometric analysis using H&E staining for muscles and osmium tetroxide for nerves. The myelinated fiber and axon diameter and the myelin sheath thickness were greater in the proximal and distal nerve segments in the LEDG compared to the IG (p ≤ 0.05). The number of myelinated fibers was greater in the distal segment of the LEDG (p ≤ 0.05). The area, circumference and diameter of the muscle fibers were larger in the LEDG than in the IG (p ≤ 0.05). The PBMT protocol used favored axonal regeneration and muscle recovery.
... 14,15 In humans, diode light has been used as a therapy for pain reduction in experimentally induced delayedonset muscle soreness, and has been reported to accelerate the wound-healing process, to change the sural nerve velocity and to be a positive influence in nerve regeneration. [16][17][18][19] As a result of these encouraging findings, opinion about the therapeutic action of non-coherent light such as diode light is changing, and nowadays is a matter of discussion. ...
... Therapy using light from other electromagnetic sources such as laser emitting has been used in the past to reduce pain and disability associated with musculoskeletal and joint diseases, in tendinosis, tendonitis, rotator cuff disorders, subacromial impingement syndrome, muscle soreness and frozen shoulder, with controversial results, both positive and negative. [2][3][4][6][7][8][9][10][11][15][16][17]19 In a previous study, our group used laser therapy in continuous mode in the treatment of shoulder and knee pain. 11,21 No differences were found when comparing the treatments, although the variety of pathologies treated could be a detrimental factor to the consistency of the results. ...
Article
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Objectives: To test the safety of the diode light therapy and evaluate the advantages of the interferential effect of two light probes versus a conventional light probe in the relief of shoulder pain and disability caused by shoulder tendinopathies. Design: Randomized single-blind pilot study. Setting: Clinical electrotherapy unit. Participants: A total of 30 patients with shoulder pain from tendinopathies. Interventions: The patients were randomly assigned into two groups. Group 1 (n = 15) received interferential light therapy generated by two independent and identical cluster probes composed of light emitting and superluminescent diodes. Similarly, two applicators were applied in group 2 (n = 15), but only one was active, as in conventional clinical therapy. Each multi-diode cluster probe was composed of seven light-emitting diodes at 600 nm and 12 superluminescent diodes at 950 nm. Main outcome measures: Pain was evaluated by visual analogue scale (VAS) at day, at night and during several shoulder movements. Shoulder functional status was measured by means of the University California Los Angeles scale (UCLA). Results: Comparison between both treatments using the Mann-Whitney U-test showed better results for the interferential treatment. There were significant differences in pain reduction during abduction (P < 0.05) and external rotation (P < 0.05), with pain reductions in abduction and external rotation of 1.5 (± 1.3) and 0.5 (± 1.0) respectively. Conclusion: Interferential light therapy was safe and effective regarding the shoulder pain reduction during abduction and external rotation movements. The estimated size sample needed for future two-treatment parallel-design studies will require about 60 patients.
... A coherent beam does not seem to be essential for modulating biological phenomena influenced by phototherapy, since luminous radiation loses its coherence upon contact with living tissue [25]. Ishiguro et al. [26] have suggested that irradiation with LEDs is advantageous to nerve regeneration. They found that the number of myelinated axons in the 1 mm sections was much larger for the LED group than for the control group. ...
Article
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This study aimed at evaluating the effects of red and blue light-emitting diodes (LED) and low-level laser (LLL) on the regeneration of the transected sciatic nerve after an end-to-end neurorrhaphy in rabbits. Forty healthy mature male New Zealand rabbits were randomly assigned into four experimental groups: control, LLL (680 nm), red LED (650 nm), and blue LED (450 nm). All animals underwent the right sciatic nerve neurotmesis injury under general anesthesia and end-to-end anastomosis. The phototherapy was initiated on the first postoperative day and lasted for 14 consecutive days at the same time of the day. On the 30th day postsurgery, the animals whose sciatic nerves were harvested for histopathological analysis were euthanized. The nerves were analyzed and quantified the following findings: Schwann cells, large myelinic axons, and neurons. In the LLL group, as compared to other groups, an increase in the number of all analyzed aspects was observed with significance level (P<0.05). This finding suggests that postoperative LLL irradiation was able to accelerate and potentialize the peripheral nerve regeneration process in rabbits within 14 days of irradiation.
... Nevertheless, more definitive experiments are needed to identify the direct target of LEDT (activation of Nrf-2 or inhibition of NFκB) in this model. Nevertheless, LEDT antioxidant activity is in conformity with previous reports, in which LEDT reduced oxidative stress in murine models of neuropathy (Fitzgerald et al., 2010; Ishiguro et al., 2010) as well as acute and chronic diabetes in rats (Lim et al., 2009). ...
Article
Background: During the last decades, the use of LEDT has increased significantly for the treatment of wound healing, analgesia and inflammatory processes. Nevertheless, scientific data on the mechanisms responsible for the therapeutic effect of LEDT are still insufficient. Thus, this study investigated the analgesic, anti-inflammatory and anti-oxidative effect of LEDT in the model of chronic inflammatory hyperalgesia. Experimental procedures: Mice injected with CFA underwent behavioral, i.e. mechanical and hot hyperalgesia; determination of cytokines levels (TNF-α, IL-1β, IL-10), oxidative stress markers (protein carbonyls and TBARS) and antioxidant enzymes (CAT and SOD). Additionally, mice were pretreated with either naloxone or fucoidin and mechanical hyperalgesia was assessed. Results: LEDT inhibited mechanical and thermal hyperalgesia induced by CFA injection. LEDT did not reduce paw edema, neither influenced the levels of TNF-α and IL1-β; although it increased the levels of IL-10. LEDT significantly prevented TBARS increase in both acute and chronic phases post-CFA injection; whereas protein carbonyls levels were reduced only in the acute phase. LEDT induced an increase in both SOD and CAT activity, with effects observable in the acute but not in the chronic. And finally, pre-administration of naloxone or fucoidin prevented LEDT analgesic effect. Conclusions: These data contribute to the understanding of the neurobiological mechanisms involved in the therapeutic effect of LEDT as well as provides additional support for its use in the treatment of painful conditions of inflammatory etiology.
... Irradiation with red/near-infrared light (R/NIR-IT, 630-1,000 nm) was developed as a therapeutic strategy for the treatment of a range of injuries and diseases, following observations of beneficial effects on minor wound healing in space (Whelan et al., 2001). Specific to the nervous system, beneficial effects have been reported following retinal degeneration (Natoli et al., 2010;Albarracin et al., 2011), CNS injury (Byrnes et al., 2005), stroke (Lapchak et al., 2007) and peripheral nerve damage (Rochkind et al., 2009;Ishiguro et al., 2010), as summarized in our recent review . While there is controversy regarding the mechanism of action of R/ NIR-IT, one hypothesis is that it acts by improving oxidative metabolism and reducing oxidative stress. ...
... Improvements following R/NIR-IT have been observed in a wide array of clinical conditions, including wound healing (Yu et al., 1997; Whelan et al., 2001 Whelan et al., , 2003), oral mucositis (Eells et al., 2004), cardial infarct size (Oron et al., 2001) and renal and hepatic complications during diabetes (Lim et al., 2009Lim et al., , 2010), although clinical efficacy is not always clear cut. Specific to the nervous system, beneficial effects have been reported following retinal degeneration (Natoli et al., 2010; Albarracin and Valter, 2012b), central nervous system (CNS) injury (Byrnes et al., 2005; Fitzgerald et al., 2010), stroke (Lapchak et al., 2007), peripheral nerve damage (Rochkind et al., 2009; Ishiguro et al., 2010) and for restless leg syndrome (Mitchell et al., 2011). However, R/NIR-IT has not been widely adopted in clinical practice for a number of reasons. ...
Article
Full-text available
Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopted in clinical practice for CNS injury or disease for a number of reasons, which include the following. The mechanism/s of action and implications of penetration have not been thoroughly addressed. The large range of treatment intensities, wavelengths and devices that have been assessed make comparisons difficult, and a consensus paradigm for treatment has not yet emerged. Furthermore, the lack of consistent positive outcomes in randomised controlled trials, perhaps due to sub-optimal treatment regimens, has contributed to scepticism. This review provides a balanced précis of outcomes described in the literature regarding treatment modalities and efficacy of R/NIR-IT for injury and disease in the CNS. We have addressed the important issues of specification of treatment parameters, penetration of R/NIR irradiation to CNS tissues and mechanism/s, and provided the necessary detail to demonstrate the potential of R/NIR-IT for the treatment of retinal degeneration, damage to white matter tracts of the CNS, stroke and Parkinson's disease.
... Most light applications in the biomedical field involve phototherapy, ie, photo wound healing, classified as photothermal treatment (acute wound closure 9 and debridement 10 ), and nonthermal photobiomodulation (chronic wound healing acceleration 11,12 and nerve regeneration 13 ). Light therapy, from daylight to specific wavelength light, including lasers, LEDs, and fluorescent lamps, has been actively employed since the first demonstration of photobiostimulation effects, ie, photobiomodulation for animal hair growth with a low-level laser (694 nm) in the late 1960s by Endre Mester, a Hungarian physician. ...
Article
Full-text available
The use of light-emitting diodes (LEDs) as therapeutic tools has been actively studied over the past few decades due to their advantages of high safety, low cost, excellent portability, and wide bandwidth. In addition, their application in biomedical fields has been expanded to such areas as nerve stimulation, photodynamic therapy, and LED-based biosensors, and LED lights are thus receiving attention as alternatives to conventional biomedical light sources such as lasers. Recently, several developments in the area of flexible inorganic LEDs along with advanced nanoelectronic technologies have pointed toward the possibility of new innovative biomethodologies in the near future. In this paper, we review the salient features of high-performance biointegrated LED applications, together with future challenges for the realization of implantable, flexible biointegrated electronic devices.
... A number of studies have explored methods by which to assess peripheral nerve injury repair and associated biomechanical properties (Taylor et al., 2008;Cheng et al., 2009;Karabekmez et al., 2009;Alrashdan et al., 2010;di Summa et al., 2010;Dong et al., 2010;Ishiguro et al., 2010;Kadam et al., 2010;Szaro and Strong, 2010;Vinik, 2010;Bielle et al., 2011;Chen et al., 2011;Dadon-Nachum et al., 2011;Korte et al., 2011;Ngeow et al., 2011;Wolford and Rodrigues, 2011;Unni et al., 2012). Wang et al. (2009) confirmed that catheters synthetized from polycaprolactone and dimethyl fumarate were strong and showed good histocompatibility, and successfully promoted differentiation and regeneration of Schwann cells in rats with 10-mm sciatic nerve defects; good growth was observed by 6 weeks after grafting. ...
Article
Full-text available
It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.
... A number of studies have explored methods by which to assess peripheral nerve injury repair and associated biomechanical properties (Taylor et al., 2008;Cheng et al., 2009;Karabekmez et al., 2009;Alrashdan et al., 2010;di Summa et al., 2010;Dong et al., 2010;Ishiguro et al., 2010;Kadam et al., 2010;Szaro and Strong, 2010;Vinik, 2010;Bielle et al., 2011;Chen et al., 2011;Dadon-Nachum et al., 2011;Korte et al., 2011;Ngeow et al., 2011;Wolford and Rodrigues, 2011;Unni et al., 2012). Wang et al. (2009) confirmed that catheters synthetized from polycaprolactone and dimethyl fumarate were strong and showed good histocompatibility, and successfully promoted differentiation and regeneration of Schwann cells in rats with 10-mm sciatic nerve defects; good growth was observed by 6 weeks after grafting. ...
Article
Full-text available
In the repair of peripheral nerve injury using autologous or synthetic nerve grafting, the magnitude of tensile forces at the anastomosis affects its response to physiological stress and the ultimate success of the treatment. One-dimensional stretching is commonly used to measure changes in tensile stress and strain; however, the accuracy of this simple method is limited. Therefore, in the present study, we established three-dimensional finite element models of sciatic nerve defects repaired by autologous nerve grafts. Using PRO E 5.0 finite element simulation software, we calculated the maximum stress and displacement of an anastomosis under a 5 N load in 10-, 20-, 30-, 40-mm long autologous nerve grafts. We found that maximum displacement increased with graft length, consistent with specimen force. These findings indicate that three-dimensional finite element simulation is a feasible method for analyzing stress and displacement at the anastomosis after autologous nerve grafting.
... suggested that hypertrophic scars exhibited a greater number of nerve fibers with more serious pathologies compared with mature scars. However, the remodeling of regenerating nerve fibers during wound healing was observed, which changed nerve innervation density Ishiguro et al., 2010;Anderson et al., 2011;Kim et al., 2011). ...
Article
Full-text available
This study aimed to use a mouse model of hypertrophic scarring by mechanical loading on the dorsum of mice to determine whether the nervous system of the skin and inflammation participates in hypertrophic scarring. Results of hematoxylin-eosin and immunohistochemical staining demonstrated that inflammation contributed to the formation of a hypertrophic scar and increased the nerve density in scar tissue.Western blot assay verified that interleukin-13 expression was increased in scar tissue. These findings suggest that inflammation and the cutaneous nervous system play a role in hypertrophic scar formation. © 2015, Editorial Board of Neural Regeneration Research. All rights reserved.
... A biphasic response was observed with stimulation and inhibition occurring at 10 J/cm 2 and 50 J/cm 2 , respectively [65]. Wound healing was accelerated and optic nerve degeneration was decreased by photobiomodulation of 660 nm at 7.5 mW/cm 2 [66]. Longer wavelengths (780-810 nm) show promise in regeneration and recovery of damaged nerves [60]. ...
Article
A synergistic-healing strategy that combines molecular targeting within a system-wide perspective is presented as the Multiple Integrated Complementary Healing Approaches: Energetics And Light (MICHAEL). The basis of the MICHAEL approach is the realization that environmental, nutritional and electromagnetic factors form a regulatory framework involved in bone and nerve healing. The interactions of light, energy, and nutrition with neural, hormonal and cellular pathways will be presented. Energetic therapies including electrical, low-intensity pulsed ultrasound and light based treatments affect growth, differentiation and proliferation of bone and nerve and can be utilized for their healing benefits. However, the benefits of these therapies can be impaired by the absence of nutritional, hormonal and organismal factors. For example, lack of sleep, disrupted circadian rhythms and vitamin-D deficiency can impair healing. Molecular targets, such as the Wnt pathway, protein kinase B and glucocorticoid signaling systems can be modulated by nutritional components, including quercetin, curcumin and Mg2+ to enhance the healing process. The importance of water and water-regulation will be presented as an integral component. The effects of exercise and acupuncture on bone healing will also be discussed within the context of the MICHAEL approach.
... This process, often referred to as photobiomodulation or NR phototherapy, promotes wound healing Eells et al. 2004;Begum et al. 2013), reduces inflammation (Kokkinopoulos et al. 2013), suppresses the expression of complement components and receptors following 24 hr exposure to cold white fluorescent light (Rutar et al. 2012), ameliorates streptozotocin diabetic retinopathy (Tang et al. 2013), attenuates cell death (Eells et al. 2004;Wong-Riley et al. 2005;Liang et al. 2006;Ying et al. 2008;del Olmo-Aguado et al. 2012) and improves the recovery rates of soft tissue injuries and myocardial infarction (Simunovic et al. 2000;Oron et al. 2001). Interestingly, high intensity NR has the ability to penetrate deeply through tissues of different types, and to ameliorate traumatic brain injury (Wu et al. 2012) as well as to induce nerve regeneration (Ishiguro et al. 2010) and brain neuronal damage (Peoples et al. 2012;Moro et al. 2013) in situ. In the case of the eye, NR has been shown to protect against photoreceptor death in situ (Rojas et al. 2008;Natoli et al. 2010;Albarracin et al. 2011;Albarracin & Valter 2012) as well as mitigate oxygeninduced degeneration (Albarracin et al. 2013). ...
Article
Purpose: To ascertain whether red light, known to enhance mitochondrial function, can blunt chemical insults to cell cultures and ischaemic insults to the rat retina. Methods: Raised intraocular pressure (IOP, 140 mmHg, 60 min) or ischaemia was delivered in complete darkness or in the presence of low intensity red light (16.5 watts/m(2) , 3000 lux, 625-635 nm) to one eye of each rat. Animals were killed at specific times after ischemia and retinas analysis for ganglion cell numbers, the localization of specific antigens or for changes in defined RNAs. RGC-5 cell cultures were also exposed to various chemical insults in the presence or absence of red light. Significant differences were determined by t-test and anova. Results: Elevation of IOP causes changes in the localization of glial fibrillary acid protein (GFAP), calretinin, calbindin, choline acetyltransferase, ganglion cell numbers and an elevation (GFAP, vimentin, HO-1 and mTORC1) or reduction (Thy-1 and Brn3a) of mRNAs in the rat retina. These negative effects to the rat retina caused by ischaemia are reduced by red light. Moreover, chemical insults to cell cultures are blunted by red light. Conclusions: Low, non-toxic levels of red light focussed on the retina for a short period of time are sufficient to attenuate an insult of raised IOP to the rat retina. Since mitochondrial dysfunctions are thought to play a major role in ganglion cell death in glaucoma, we propose the potential use of red light therapy for the treatment of the disease.
... Nevertheless, more definitive experiments are needed to identify the direct target of LEDT (activation of Nrf-2 or inhibition of NFjB) in this model. Nevertheless, LEDT antioxidant activity is in conformity with previous reports, in which LEDT reduced oxidative stress in murine models of neuropathy (Fitzgerald et al., 2010;Ishiguro et al., 2010) as well as acute and chronic diabetes in rats (Lim et al., 2009). The relationship between increased levels of antiinflammatory cytokines and inhibition of oxidative stress by LEDT is not yet documented. ...
... Because we could not find any accurate evidence about this matter at the beginning of this project 34,35 and the sciatic nerve lesions bilaterally could be seen in previous data. 36,37 We, therefore, attempted to study bilaterally. Although TeTx enhanced the nerve regeneration in rats, we cannot conclude whether it can be used in humans to enhance regeneration. ...
Article
ObjectThe purpose was to investigate the effects of local tetanus toxin (TeTx) application on sciatic nerve regeneration following a rat model of transection injury.Methods After both sciatic nerves were transected and repaired with three epineural sutures, 12 male Wistar albino rats were divided into two groups. 0.25 ml (2.5 flocculation units) TeTx was injected into a piece of absorbable gelatin sponge in TeTx group. In controls, 0.25 ml saline injected. Assessments were performed by using climbing degrees, compound muscle action potentials (CMAPs) and histological parameters (axon number and axonal diameter) 12th week.ResultsCMAPs amplitudes were 11.6 ± 4.7 mV and 1.4 ± 1.3 mV in gastrocnemius and interdigital muscles in TeTx group (5.8 ± 2.4 mV and 0.2 ± 0.1 mV, P < 0.05). Climbing degrees were significantly different (61.6 ± 1.7 vs. 38.3 ± 2.6, P < 0.05). Total axon numbers were higher (1341.1 ± 57.3 vs. 877.5 ± 34.9, P < 0.05) and the mean axon diameter was smaller (4.2 ± 2.1 vs. 2.5 ± 1.9, P < 0.05) in the TeTx group.Conclusion This preliminary study firstly demonstrated the effectiveness of TeTx on nerve repair in experimental sciatic rat model based on functional, electromyographic and histological parameters. © 2014 Wiley Periodicals, Inc. Microsurgery, 2014.
... Nevertheless, more definitive experiments are needed to identify the direct target of LEDT (activation of Nrf-2 or inhibition of NFjB) in this model. Nevertheless, LEDT antioxidant activity is in conformity with previous reports, in which LEDT reduced oxidative stress in murine models of neuropathy (Fitzgerald et al., 2010;Ishiguro et al., 2010) as well as acute and chronic diabetes in rats (Lim et al., 2009). The relationship between increased levels of antiinflammatory cytokines and inhibition of oxidative stress by LEDT is not yet documented. ...
... Eells et al., 2003;Karu, 1999;Wong-Riley et al., 2005)). Most importantly, red light has the ability to penetrate through different depths of tissues pending on intensity, and has even been shown to ameliorate traumatic brain injury Wu et al., 2012)) as well as to induce CNS nerve regeneration (Ishiguro et al., 2010) and blunt neuronal damage (Moro et al., 2013;Peoples et al., 2012) in situ. ...
Article
Light of different wave-lengths have the potential to interact with four major mitochondrial protein complexes that are involved in the generation of ATP. Neurones of the central nervous system have an absolute dependence on mitochondrial generated ATP. Laboratory studies show that short-wave or blue light (400–480 nm) that impinges on the retina affect flavin and cytochrome constituents associated with mitochondria to decrease the rate of ATP formation, stimulate ROS and results in cell death. This suggests that blue light could potentially have a negative influence on retinal ganglion cell (RGC) mitochondria that are abundant and not shielded by macular pigments as occurs for photoreceptor mitochondria. This might be of significance in glaucoma where it is likely that RGC mitochondria are already affected and therefore be more susceptible to blue light. Thus simply filtering out some natural blue light from entering the eye might be beneficial for the treatment of glaucoma.
... Specifically in the eye, red light protects against photoreceptor death (Albarracin et al., 2011;Albarracin and Valter, 2012;Natoli et al., 2010;Osborne et al., 2016aOsborne et al., , 2016bRojas et al., 2008), ameliorates diabetic retinopathy (Saliba et al., 2015;Tang et al., 2013), reduces dendropathy (Beirne et al., 2016), mitigates oxygeninduced degeneration (Albarracin et al., 2013) and attenuates histopathological changes in the retina induced by a variety of insults (Albarracin et al., 2011(Albarracin et al., , 2013Albarracin and Valter, 2012;Begum et al., 2013;Eells et al., 2004;Natoli et al., 2010;Rojas et al., 2008;Wong-Riley et al., 2005). It has also been reported that red light can ameliorate injury to the brain and spinal cord Ishiguro et al., 2010;Moro et al., 2013;Peoples et al., 2012;Wu et al., 2012) in animals. We are unaware of any studies to date that have demonstrated that red light can preserve the corneal endothelium in situ. ...
... Treatment then was provided until symptoms were resolved, and the LCI returned to normal. In the absence of a baseline LCI, treatment was provided until symptoms were resolved, and the LCI stabilized at the lower level [1][2][3][4][5][6][7][8][9][10][11][12][13]. ...
... Of interest to sports medicine are observations of improved collagen deposition in skeletal muscle [8], reduced oedema [9] and inflammatory infiltrates into tissues [8,10,11], improved bone density [12,13], the acceleration of recovery from tendinopathy [14], sprains [9], and peripheral nerve damage [15,16], and the reduction of pain [11,17]. PBM has also been shown to be neuroprotective without adverse effects [18], improve functional outcomes after stroke in rabbits [19] and spinal cord injury in rodents [10,11], as well as prevent dopaminergic cell loss in Parkinson's disease animal models [20]. ...
Article
Red‐light treatment is emerging as a novel therapy for promoting tissue recovery but data on red‐light penetration through human tissues are lacking. We aimed to: i) determine the effect of light irradiance, tissue thickness, skin tone, sex, and bone/muscle content on 660 nm light penetration through common sites of sports injuries, and ii) establish if cadaver tissues serve as a useful model for predicting red‐light penetration in live tissues. Live and cadaver human tissues were exposed to 660 nm light at locations across the skull, spinal cord and upper and lower limbs. Red‐light was produced by a light emitting diode array of various irradiances (15‐500 mW/cm²) and measured by a light‐probe positioned on the tissue surface opposite the LEDs. 100 mW/cm² successfully penetrated tissue < 50 mm thick; a disproportionate irradiance increase was required to achieve deeper penetration. Penetration was unaffected by skin tone, increased with irradiance and relative bone/muscle composition, and decreased with greater tissue thickness and in males. Live and cadaveric tissue penetration did not differ statistically for tissues < 50 mm but cadavers required more red‐light to penetrate > 50 mm. These results assist clinicians and researchers in determining red‐light treatment intensities for penetrating human tissues. This article is protected by copyright. All rights reserved.
... Improvements following R/NIR-IT have been observed in a wide array of clinical conditions, including wound healing (Yu et al., 1997; Whelan et al., 2001 Whelan et al., , 2003), oral mucositis (Eells et al., 2004), cardial infarct size (Oron et al., 2001) and renal and hepatic complications during diabetes (Lim et al., 2009Lim et al., , 2010), although clinical efficacy is not always clear cut. Specific to the nervous system, beneficial effects have been reported following retinal degeneration (Natoli et al., 2010; Albarracin and Valter, 2012b), central nervous system (CNS) injury (Byrnes et al., 2005; Fitzgerald et al., 2010), stroke (Lapchak et al., 2007), peripheral nerve damage (Rochkind et al., 2009; Ishiguro et al., 2010) and for restless leg syndrome (Mitchell et al., 2011). However, R/NIR-IT has not been widely adopted in clinical practice for a number of reasons. ...
Article
Full-text available
Abstract Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopted in clinical practice for CNS injury or disease for a number of reasons, which include the following. The mechanism/s of action and implications of penetration have not been thoroughly addressed. The large range of treatment intensities, wavelengths and devices that have been assessed make comparisons difficult, and a consensus paradigm for treatment has not yet emerged. Furthermore, the lack of consistent positive outcomes in randomised controlled trials, perhaps due to sub-optimal treatment regimens, has contributed to scepticism. This review provides a balanced précis of outcomes described in the literature regarding treatment modalities and efficacy of R/NIR-IT for injury and disease in the CNS. We have addressed the important issues of specification of treatment parameters, penetration of R/NIR irradiation to CNS tissues and mechanism/s, and provided the necessary detail to demonstrate the potential of R/NIR-IT for the treatment of retinal degeneration, damage to white matter tracts of the CNS, stroke and Parkinson's disease.
Article
Five decades after the first documented use of a laser for wound healing, research in light therapy has yet to elucidate the underlying biochemical pathways causing its effects. The aim of this review is to summarize the current research into the biochemical mechanisms of light therapy in order to better direct future studies. The implication of cytochrome c oxidase as the photoacceptor modulating light therapy is reviewed, as are the predominant hypotheses of the biochemical pathways involved in the stimulation of wound healing, cellular proliferation, production of transcription factors and other reported stimulatory effects.
Article
In this study, GCC protein was used for the first time to construct a biodegradable conduit for peripheral nerve repair. The GCC was highly stable with a sufficiently high level of mechanical properties and it was non-toxic and non-apoptotic which could maintain the survival and outgrowth of Schwann cells. Noninvasive bioluminescence imaging accompanied with histochemical assessment showed the GCC was highly biocompatible after subcutaneous implantation in transgenic mice. Electrophysiology, labeling of calcitonin gene-related peptide in the lumbar spinal cord and histology analysis also showed a rapid morphological and functional recovery for disrupted rat sciatic nerves repaired with the GCC conduits. Therefore, we conclude that the GCC can offer great nerve regeneration characteristics and can be a promising material for the successful repair of peripheral nerve defects.
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Peripheral nerve injury is a common clinical disease, to study the effects of the physical therapy on the regeneration of the injured sciatic nerve, and provide a reference for clinical treatment. Sixty-four female adult Wistar rats (weighing 252-365 g) were chosen and randomly divided into 4 groups (n = 16): group A, group B, group C, and group D. The experimental model of sciatic nerve defect was established by crushing the right sciatic nerve in groups B, C, and D; group A served as the control group without crushing. At 2 days after injury, no treatment was given in group B, electrical stimulation in group C, and combined physical therapies (decimeter and infrared ray) in group D. At 0, 7, 14, and 30 days after treatment, the sciatic nerve function index (SFI) and the motor nerve conduction velocity (MNCV) were measured, and morphological and transmission electron microscopy (TEM) examinations were done; at 30 days after treatment, the morphological evaluation analysis of axons was performed. At 0 and 7 days after treatment, the SFI values of groups B, C, and D were significantly higher than that of group A (P < 0.05); at 14 and 30 days after treatment, the SFI value of group D decreased significantly, no significant difference was observed between group D and group A (P > 0.05) at 30 days; whereas the SFI values of groups B and C decreased, showing significant difference when compared with the value of group A (P < 0.05). At 0, 7, and 14 days after treatment, the MNCV values of groups B, C, and D were significantly lower than that of group A (P < 0.05), and there were significantly differences between group B and groups C, D (P < 0.05); at 14 days, the MNCV value of group D was significantly higher than that of group C (P < 0.05); and at 30 days, the MNCV values of groups B and C were significantly lower than that of group A (P < 0.05), but there was no significant difference between group D and group A (P > 0.05). At 0 and 7 days, only collagen and lipid were observed by TEM; at 14 and 30 days, many Schwann cells and perineurial cells in regeneration axon were observed in groups B, C, and D, especially in group D. Automated image analysis of axons showed that there was no significant difference in the number of myelinated nerve fibers, axon diameter, and myelin sheath thickness between group D and group A (P > 0.05), and the number of myelinated nerve fibers and axon diameter of group D were significantly higher than those of groups B and C (P < 0.05). Physical therapy can improve the regeneration of the injured sciatic nerve of rats.
Article
The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. Results: LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.
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Purpose: Despite the extensive efforts to treat the leading cause of neurodegenerative diseases (ND), a little progress has been reported. Red light might affect ND through many specific mechanisms. The purpose of this investigation is to explore the effect of red light on the expression of low-density lipoprotein receptor-1 (LRP-1) and transient receptor potential ankyrin-1 (TRPA-1) gene in the hippocampus, and the serum melatonin level (SML) of the LPS-induced neuro-inflammated rats. Materials and methods: Red-light therapy was implemented using a wavelength 630 nm under different light conditions and the passive avoidance (PA) and Y-Maze tests were employed to assess memory performance. To evaluate the LRP-1 and TRPA-1 genes expression, q-RT-PCR was performed. To measure the SML, ELISA was performed before and after the red-light radiation. Results: Lipopolysaccharide (LPS) caused memory impairment in both behavioral tests. Red-light therapy improved PA memory in all light conditions (p < 0.001). However, in Y-maze, only the red-light radiation during light and dark cycles, improved memory (p < 0.01and p < 0.001, respectively). In addition, red-light radiation caused significant increase in SML (P < 0.05). The LRP-1 and TRPA-1 genes expression increased significantly during the dark phase in the red light radiated group compared to non-radiated group (P < 0.001). Conclusions: Taken together, the results suggest that red-light therapy can reduce the complications of memory impairment in rats. This study has found that red-light therapy demonstrates higher effect during the period of dark phase compared to light phase. No doubt, further experimental studies would help us to establish a greater degree of accuracy on this matter.
Article
The aim of this study was to assess the effect of low- level laser therapy (LLLT) on fibroblast proliferation on wound repair of rats with Iron deficiency anemia since there is no reports on literature about this subject. Iron deficiency anemia was induced on 36 newborn rats then an excisional wound was created on the dorsum of the animals which were divided into four groups: (I) - non-anemic, (II) - Anemic, (III) - non-anemic + LLLT, (IV) Anemic+ LLLT. The animals in each group were sacrificed at 7, 14 and 21 days. Laser irradiation was performed on each group (lambda660nm,40Mw,CW) by contact mode with a dose of 2,5J/ cm2 in four points on the area of the wound and total of 10J/cm2 per session. Data were evaluated by analysis of variance (ANOVA) followed by Paired t-test. The results showed LLLT was able to stimulate fibroblastic proliferation in rats with iron deficiency anemia at the 21st day while at control group (III) no statistically significant differences was found.
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Neurons depend on their mitochondria for optimum function and become susceptible with age. Mitochondrial function is gradually impaired during aging because more electrons are converted to reactive oxygen species rather than being converted to ATP. Retinal ganglion cell mitochondria are additionally affected in glaucoma because of reduced oxygen delivery. Thus, targeting neuronal mitochondria to enhance their function as in glaucoma and aspects associated with aging provides potential ways of attenuating degenerating diseases. A substance worthy of mention is rapamycin, which affects regulated in development and DNA damage 1 (REDD1), and is known to enhance mitochondrial function. REDD1 appears to be prominent in retinal ganglion cells. An alternative exciting non-invasive approach is to use red light therapy that enhances mitochondrial function.
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Energy harvesting technology utilising mechanical energy sources is a promising approach for the sustainable, independent, and permanent operation of a variety of flexible electronics. A new concept of fully-flexible light-emitting system self-powered by high-performance piezoelectric thin film energy harvester has been first established by manipulating highly-robust flexible vertical-structured light emitting diodes (f-VLEDs). The f-VLEDs fabricated by anisotropic conductive film bonding and entire wafer etching show stable and durable performance during periodic mechanical deformations. A high-output energy harvester capable of generating up to 140 V and 10 μA can be flexible via laser lift-off (LLO) process widely used in industries in a safe and robust manner. In particular, this LLO process is of great benefit to fabrication of mechanically stable flexible piezoelectric devices, not causing any degradation of piezoelectric properties. In this self-powered all-flexible electronic system with light-emitting can be spontaneously achieved by the produced electricity from the flexible thin film generator by slight biomechanical energy with no externally applied energy storage. This conceptual technology of self-powering based on conversion of mechanical energy to electrical energy can open a facile and robust avenue to diverse self-powered bio-implantable applications as well as commercial display applications.
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Mild and moderate traumatic brain injury, including post concussion syndrome, (mTBI) have been a subject of increasing interest in medicine. It is now recognized that the severity of the initial physical trauma presentation may not indicate the extent of impact on neurons or the significance of both short and long term consequences of the injury. The initial injury and resulting cascade of neuronal responses to injury have consequences that can be manifested by overt symptoms such as chronic headaches, anxiety, depression, insomnia, social withdrawal, and seizures. Additionally, there often are more subtly manifested symptoms that may include impairment in working memory and information processing speed, dysautonomia, or other indications of CNS dysfunction. The unfortunate impact of unrecognized or undertreated mTBI is that it may lead to long term disability for the patient in the form of impaired ADL capacity or employability. There is also an additional concern of neurodegeneration in some subsets of mTBI patients.
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Mild traumatic brain injury (mTBI), including concussion syndromes, have been a subject of increasing interest both in and out of medicine. The 2014 World Health OraganizationTask Force-International Collaboration on Mild Traumatic Brain Injury Prognosis 2014 (ICoMP) report states it is now considered a " prominent public health problem ". J. David Cassidy, DC, PhD, DrMedSc , a Task Force member, and others are beginning to raise awareness of chiropractic's responsibility and its role in managing mTBI. The message is that chiropractic physicians are uniquely positioned to diagnose and treat mild traumatic brain injury (mTBI.) As neuromuscular specialists, chiropractors see a large percentage of a patient population with a history of traumatic head and neck injuries that result in mTBI. At is issue is that all post mTBI care is plagued by limited treatment modalities. Recent research has demonstrated LLLT delivered transcranially is both safe and effective in treatment of mTBI and other conditions of the central nervous system. Many chiropractic physicians recognize the effectiveness of low level laser therapy (LLLT) in neuromusculoskeletal treatment but have not realized its potential when utilized transcranially. It has largely gone unutilized at the clinical level. Current research is a wake-up call for chiropractic physicians to consider transcranial low level laser therapy (tLLLT) in mTBI cases and its beneficial effects. The Problem: Mild TBI often goes undiagnosed, untreated, or under treated. In cases of mild TBI, the term " mild " is used in reference to the severity of the initial physical trauma that caused the injury and does not indicate the degree of brain trauma or the severity of the consequences of the injury. These consequences are frequently manifested by impairment of working memory and information processing speed. Other secondary symptoms include chronic headaches, anxiety, depression, insomnia, social withdrawal, seizures and other indications of CNS dysfunction. These consequences may lead to long term impairment in the form of decreased ADL capacity or even employability. An additional concern is neurodegeneration which has become a serious concern in some subsets of mTBI patients. The WHO report recommends that DCs " facilitate a path to good recovery for MTBI patients through early education and positive reassurance as well as by providing treatments aimed at reducing associated spine and headache-related pain. " And goes on to warn about " excessive diagnostic testing or applying diagnostic labels " and " Integrating care with a patient's primary medical physician is
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Background: Monochromatic infrared energy (MIRE) or phototherapy has been used to improve plantar sensitivity and pain in lower limbs of patients with diabetic sensorimotor peripheral neuropathy (DSPN), but the available primary results are inconsistent. Objective: To review systematically the effects of MIRE on plantar sensitivity and neuropathic pain in patients with DSPN. Methods: Medline, EMBASE, Cochrane CENTRAL, and Google Scholar were searched up to September 2016. Randomized controlled trials addressing the effects of MIRE on plantar sensitivity and neuropathic pain in patients with DSPN were selected. Study inclusion, risk of bias and quality assessment, and data extraction were completed by two independent reviewers. Results: Of 2549 records identified, six studies met the selection criteria, with 304 patients (594 feet) randomized. MIRE was not associated with improvement in plantar tactile sensitivity (SMD=0.22, 95%CI -0.07 to 0.51, low quality of evidence). Subgroups of studies with short-term (up to 2 weeks) follow-up showed significant improvement in plantar sensitivity (SMD=0.41, 95% CI 0.18-0.64). Neuropathic pain increased significantly in patients who received MIRE (MD=0.49, 95% CI 0.30-0.68, low quality of evidence). Conclusions: There was limited evidence that MIRE results in short-term improvement of tactile sensitivity probably not sustained over time. Limited evidence also suggested that MIRE does not provide relief for neuropathic pain. As quality of evidence is low, further studies are likely to change the estimated effect.
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A new therapeutic instrument using ultrasound and a light-emitting diode with an adjustable optical lens was introduced for suppressing HeLa cell proliferation. A focused-type ultrasonic transducer can transmit an acoustic signal to focus the ultrasound signal onto a certain spot. Likewise, the light-emitting diode light is noncoherent and divergent, and therefore, a telephoto lens is also needed to focus light on certain desired areas. This combinational instrument, which provides an adjustable focus for the transmitted light, could be useful for differentiating the treatment and nontreatment ranges when utilizing light-emitting diodes and ultrasound sources as treatment devices. The telephoto lens can provide an adjustable illumination area of 7.06 mm × 4.01 mm and 14.05 mm × 11.67 mm in focus and defocus modes, respectively, and ultrasound can also provide adjustable acoustic beam diameters of 7 mm and 14 mm at the −6 dB intensity levels, respectively. The developed therapeutic instrument was tested to demonstrate that HeLa cell proliferation was suppressed with the ultrasound-light-emitting diode controlled by a telephoto lens. Owing to the mechanical and thermal effects caused by the ultrasound and light-emitting diode, the control of cell density by focused and defocused beams on Day 2 is shown as 99.38 ± 0.32%, 51.33 ± 10.89%, and 37.70 ± 1.95%, respectively. Therefore, we confirm that the developed ultrasound-light-emitting diode with an adjustable telephoto lens can suppress the proliferation of HeLa cells.
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The purpose of this study was to determine the effects of prophylactic near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone marrow transplant (BMT) recipients. Oral mucositis (OM) is a frequent side effect of chemotherapy that leads to increased morbidity. Near-infrared light has been shown to produce biostimulatory effects in tissues, and previous results using near-infrared lasers have shown improvement in OM indices. However, LEDs may hold greater potential for clinical applications. We recruited 32 consecutive pediatric patients undergoing myeloablative therapy in preparation for BMT. Patients were examined by two of three pediatric dentists trained in assessing the Schubert oral mucositis index (OMI) for left and right buccal and lateral tongue mucosal surfaces, while the patients were asked to rate their current left and right mouth pain, left and right xerostomia, and throat pain. LED therapy consisted of daily treatment at a fluence of 4 J/cm(2) using a 670-nm LED array held to the left extraoral epithelium starting on the day of transplant, with a concurrent sham treatment on the right. Patients were assessed before BMT and every 2-3 days through posttransplant day 14. Outcomes included the percentage of patients with ulcerative oral mucositis (UOM) compared to historical epidemiological controls, the comparison of left and right buccal pain to throat pain, and the comparison between sides of the buccal and lateral tongue OMI and buccal pain. The incidence of UOM was 53%, compared to an expected rate of 70-90%. There was also a 48% and 39% reduction of treated left and right buccal pain, respectively, compared to untreated throat pain at about posttransplant day 7 (p < 0.05). There were no significant differences between sides in OMI or pain. Although more studies are needed, LED therapy appears useful in the prevention of OM in pediatric BMT patients.
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Light close to and in the near-infrared range has documented benefits for promoting wound healing in human and animals. However, mechanisms of its action on cells are poorly understood. We hypothesized that light treatment with a light-emitting diode array at 670 nm (LED) is therapeutic in stimulating cellular events involving increases in cytochrome oxidase activity. LED was administered to cultured primary neurons whose voltage-dependent sodium channels were blocked by tetrodotoxin. The down-regulation of cytochrome oxidase activity by TTX was reverted to control levels by LED. LED alone also up-regulated enzyme activity. Thus, the results are consistent with our hypothesis that LED has a stimulating effect on cytochrome oxidase in neurons, even when they have been functionally silenced by TTX.
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The purpose of this study was to determine the effects of prophylactic near-infrared light therapy from light-emitting diodes (LEDs) in pediatric bone marrow transplant (BMT) recipients. Oral mucositis (OM) is a frequent side effect of chemotherapy that leads to increased morbidity. Near-infrared light has been shown to produce biostimulatory effects in tissues, and previous results using near-infrared lasers have shown improvement in OM indices. However, LEDs may hold greater potential for clinical applications. We recruited 32 consecutive pediatric patients undergoing myeloablative therapy in preparation for BMT. Patients were examined by two of three pediatric dentists trained in assessing the Schubert oral mucositis index (OMI) for left and right buccal and lateral tongue mucosal surfaces, while the patients were asked to rate their current left and right mouth pain, left and right xerostomia, and throat pain. LED therapy consisted of daily treatment at a fluence of 4 J/cm(2) using a 670-nm LED array held to the left extraoral epithelium starting on the day of transplant, with a concurrent sham treatment on the right. Patients were assessed before BMT and every 2-3 days through posttransplant day 14. Outcomes included the percentage of patients with ulcerative oral mucositis (UOM) compared to historical epidemiological controls, the comparison of left and right buccal pain to throat pain, and the comparison between sides of the buccal and lateral tongue OMI and buccal pain. The incidence of UOM was 53%, compared to an expected rate of 70-90%. There was also a 48% and 39% reduction of treated left and right buccal pain, respectively, compared to untreated throat pain at about posttransplant day 7 (p < 0.05). There were no significant differences between sides in OMI or pain. Although more studies are needed, LED therapy appears useful in the prevention of OM in pediatric BMT patients.
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Methanol intoxication produces toxic injury to the retina and optic nerve, resulting in blindness. The toxic metabolite in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit the essential mitochondrial enzyme, cytochrome oxidase. Photobiomodulation by red to near-IR radiation has been demonstrated to enhance mitochondrial activity and promote cell survival in vitro by stimulation of cytochrome oxidase activity. The present studies were undertaken to test the hypothesis that exposure to monochromatic red radiation from light-emitting diode (LED) arrays would protect the retina against the toxic actions of methanol-derived formic acid in a rodent model of methanol toxicity. Using the electroretinogram as a sensitive indicator of retinal function, we demonstrated that three brief (2 min, 24 s) 670-nm LED treatments (4 J/cm(2)), delivered at 5, 25, and 50 h of methanol intoxication, attenuated the retinotoxic effects of methanol-derived formate. Our studies document a significant recovery of rod- and cone-mediated function in LED-treated, methanol-intoxicated rats. We further show that LED treatment protected the retina from the histopathologic changes induced by methanol-derived formate. These findings provide a link between the actions of monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro and retinoprotection in vivo. They also suggest that photobiomodulation may enhance recovery from retinal injury and other ocular diseases in which mitochondrial dysfunction is postulated to play a role.
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The purpose of this study was to assess the changes in gene expression of near-infrared light therapy in a model of impaired wound healing. Background Data: Light-Emitting Diodes (LED), originally developed for NASA plant growth experiments in space, show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper we present the effects of LED treatment on wounds in a genetically diabetic mouse model. Polyvinyl acetal (PVA) sponges were subcutaneously implanted in the dorsum of BKS.Cg-m +/+ Lepr(db) mice. LED treatments were given once daily, and at the sacrifice day, the sponges, incision line and skin over the sponges were harvested and used for RNA extraction. The RNA was subsequently analyzed by cDNA array. Our studies have revealed certain tissue regenerating genes that were significantly upregulated upon LED treatment when compared to the untreated sample. Integrins, laminin, gap junction proteins, and kinesin superfamily motor proteins are some of the genes involved during regeneration process. These are some of the genes that were identified upon gene array experiments with RNA isolated from sponges from the wound site in mouse with LED treatment. We believe that the use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the Defense Advanced Research Projects Agency (DARPA) and NASA Marshall Space Flight Center-SBIR Program.
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Far red and near infrared (NIR) light promotes wound healing, but the mechanism is poorly understood. Our previous studies using 670 nm light-emitting diode (LED) arrays suggest that cytochrome c oxidase, a photoacceptor in the NIR range, plays an important role in therapeutic photobiomodulation. If this is true, then an irreversible inhibitor of cytochrome c oxidase, potassium cyanide (KCN), should compete with LED and reduce its beneficial effects. This hypothesis was tested on primary cultured neurons. LED treatment partially restored enzyme activity blocked by 10–100 μm KCN. It significantly reduced neuronal cell death induced by 300 μm KCN from 83.6 to 43.5%. However, at 1–100 mm KCN, the protective effects of LED decreased, and neuronal deaths increased. LED significantly restored neuronal ATP content only at 10 μm KCN but not at higher concentrations of KCN tested. Pretreatment with LED enhanced efficacy of LED during exposure to 10 or 100 μm KCN but did not restore enzyme activity to control levels. In contrast, LED was able to completely reverse the detrimental effect of tetrodotoxin, which only indirectly down-regulated enzyme levels. Among the wavelengths tested (670, 728, 770, 830, and 880 nm), the most effective ones (830 nm, 670 nm) paralleled the NIR absorption spectrum of oxidized cytochrome c oxidase, whereas the least effective wavelength, 728 nm, did not. The results are consistent with our hypothesis that the mechanism of photobiomodulation involves the up-regulation of cytochrome c oxidase, leading to increased energy metabolism in neurons functionally inactivated by toxins.
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Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.
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This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as "photobiomodulation," uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.
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The aim of this study was to compare the angiogenic effects of laser and light-emitting diode (LED) illumination on wounds induced in rats, with varied fluence. The LED is an alternative light source that accelerates wound healing, and its efficiency concerning the angiogenic effect was compared to low-level laser therapy (LLLT). The experimental model consisted of a circular wound inflicted on the quadriceps of 120 rats, using a 15-mm-diameter "punch." Animals were divided randomly into five groups: two groups of laser, with dosages of 5 and 20 J/cm(2), respectively, two groups of LED, also with dosages of 5 and 20 J/cm(2), and a control group. Six hours after wound infliction, the treated groups received the diverse applications accordingly and were irradiated every 24 h. Angiogenesis was studied through histomorphometry on days 3, 7, 14, and 21 after the wounds were inflicted. On days 3, 7, and 14, the proliferation of blood vessels in all irradiated groups was superior in comparison to those of the control group (p < 0.05). Treatment with fluence of 5 J/cm(2) was better than the laser group with 20 J/cm(2) on day 21. Red LLLT and LED demonstrated expressive results in angiogenesis. Light coherence was shown not to be essential to angiogenesis. However, further studies are needed in order to investigate the photobiomodulatory effects of LED in relation to LLLT in various biological tissues.
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This paper reviews studies on the basic principles of biostimulation of wound healing by various low-energy lasers. It looks at the mechanism of action of biostimulation as well as the lasers effect on cell proliferation, collagen synthesis, and would healing.
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The use of tubes as an alternative to primary nerve suture in fresh nerve transections has been introduced as a biologic approach to nerve injuries, creating optimal conditions for axonal regeneration over a short empty space intentionally created between the proximal and distal nerve ends. The idea may seem controversial and has been criticized using the arguments that silicone in itself may create problems like inflammation and the tube may compress the nerve ends. With the use of appropriately sized tubes for bridging a maximum 5-mm gap in human median and ulnar nerves, the authors have found the technique to be useful and persistent at follow-up examinations for up to 4 to 5 years. In addition, from the intellectual point of view, the principle illustrates the concept by which emphasis is placed on the intrinsic healing capacities of the nerve rather than on the technical skill of the surgeon. The thin mesothelial lining found around the silicone tube lacks primary inflammatory signs at follow-up after 1 year, and no signs of compression are seen. It may be an advantage because it allows sliding of the repair site against the surrounding tissues. Tubes made of bioresorbable material may seem ideal, but they may introduce new problems associated with the resorption process in terms of a substantial unrestricted macrophage invasion, fibrosis, and disorganized axonal growth. For an extended nerve defect, the use of autologous nerve grafts is still the gold standard, because no tubular conduit or other conduit has so far proved equal to autologous nerve grafts, at least not for reconstruction of human median and ulnar nerve trunks. Alternatives other than tubes are currently being developed and investigated. For the future, the use of tubes for repair and reconstruction of nerves may have interesting potentials, because such a structure allows several types of tissue engineering. Various matrices containing, for instance, appropriate cells, factors, or other stimulating agents can be introduced in the tube lumen and can also be incorporated in a slow-release form in the walls of the tube and manipulated. Cultured Schwann cells or other cellular components, with or without manipulated production machinery, are probably the cells of choice for introduction in the tubes. Tubes may thus prove to be interesting alternatives to conventional repair techniques for primary repair of nerves and for reconstruction of segmental defects and for neuroma treatment in the future.
Article
The spatial-temporal progress of nerve regeneration was examined in silicone chambers of three different volume capacities: 11, 25, and 75 μl. In all chambers, the stumps of a transected rat sciatic nerve were sutured into the ends of the chamber leaving a 10 mm gap between the stumps. Chambers were implanted empty (E chambers) or prefilled with saline (PF chambers). A coaxial and continuous fibrin matrix had formed in all chambers by 1 week. In E chambers, the matrices had a proximal-distal taper that was more pronounced in E25 and E75 chambers due to significantly larger matrix diameters in the proximal region. At 3 weeks, vascular and Schwann cell migration and axonal regeneration were less advanced in the E25 and E75 than in the control E11 chambers. The retardation correlated with the presence of an avascular organization of circumferential cells. Saline prefill-ing affected the caliber and density of fibrin fibers in the 1 week matrices of PF25 and PF75 chambers. The matrices did not have a prominent taper and diameters were progressively larger with increasing chamber volume. Saline prefilling did not affect regeneration progress in 3 week PF11 chambers but did enhance regeneration in the PF25 chambers; a 1.5-fold larger diameter nerve formed at 3 weeks that contained 2,6-fold more axons. Progress in the PF75 chamber was retarded. We conclude that the volume, timing, and nature of the fluid filling a silicone chamber have significant influence on the formation of fibrin matrices. Alterations in matrix formation correlate with substantial changes in the subsequent progress of intrachamber regeneration events.
Article
The presence of neuronotrophic factors (NTFs) in noninjured sciatic nerve extract and the course of their accumulation from 3 h to 30 days after nerve transection was examined. Rat sciatic nerves were transected and their proximal and distal stumps sutured into the openings of cylindrical silicone chambers leaving a 10-mm interstump gap. Previous studies had shown that regeneration occurs in chambers containing both stumps but is absent in chambers lacking the distal stump. Chambers became completely filled with fluid 10 to 12 h after implantation. Fluid from chambers without nerve stumps (open-ended) implanted adjacent to nerve-containing chambers had markedly lower trophic activities than those containing one or both stumps. In fluid collected from chambers containing both proximal and distal nerve stumps, the highest titers of NTFs directed to sensory neurons were measured at 3 h posttransection whereas the highest titers of NTFs directed to sympathetic and spinal cord neurons were detected at 1 and 3 days, respectively. Chambers containing only the proximal or only the distal stumps showed similar temporal dynamics for sensory and sympathetic NTFs. Sensory and sympathetic neuronotrophic activity in extracts of proximal and distal stumps followed a similar temporal course to those in chamber fluid. Extracts of nonlesion nerve segments 5 mm from the transection site contained higher sensory and lower sympathetic trophic activity than extracts including the transection site. Spinal cord activity was undetectable in all extracts. Antiserum to nerve growth factor had no effect on fluid or extracts containing high sensory or sympathetic activities. These observations suggested that (i) some NTFs may be present in normal nerves and others may be synthesized or accumulated in response to nerve injury, (ii) sensory, sympathetic, and spinal cord NTFs are separate agents and immunochemically distinct from nerve growth factor, (iii) NTFs predominantly originate from nerve stumps rather than from surrounding fluid, and (iv) proximal and distal nerve stumps accumulate and release NTFs at similar rates.
Article
Rat sciatic nerves can be transected and their proximal and distal stumps sutured into the openings of cylindrical silicone chambers. Anatomical regeneration has been demonstrated across 10 mm long chambers containing both stumps, although little or no axonal outgrowth occurs in chambers omitting the distal stump or exceeding the 10 mm length. We have previously shown that chambers containing both proximal and distal stumps accumulate within days of implantation a clear fluid containing neuronotrophic factors (NTFs) directed to neurons from neonatal mouse dorsal root ganglia. We report here that these chamber fluids also have considerable neuronotrophic activity for chick embryo neurons from embryologic day 4 (E4) lumbar spinal cord, E12 sympathetic ganglia, E12 (but not E8) dorsal root ganglia and E8 ciliary ganglia. Thus, the neuronal types supported by trophic factors of these fluids include all those which contribute axons to the sciatic nerve, namely sensory, spinal motor, and sympathetic. In fluid collected 1 week after implantation, NTF levels directed to different neurons varied independently from one another in chambers with different nerve insertions, suggesting that these activities reside in separate factors. Fluid collected from chamber arrangements allowing little proximal fiber regrowth did not always contain correspondingly lower titers of NTFs. However, generally higher titers of all NTFs were found in chambers containing either or both nerve stumps that in nerve-free chambers. Fluids collected from nerve-containing chambers were subjected to heat, dialysis or trypsin treatments. The behavior of their neuronotrophic activities suggests their association with proteins.
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The concept of the nerve tube has been a major topic of research in the field of peripheral nerve regeneration for more than 25 years. The first nerve tubes are currently available for clinical use. This article gives an overview of the experimental and clinical data on nerve tubes for peripheral nerve repair and critically analyzes the data on which the step from laboratory to clinical use is based. In addition, it briefly discusses the different modifications to the common single lumen nerve tubes that may improve the results of generation.
Article
The fluid accumulating in silicone nerve regeneration chambers implanted between the cut ends of rat sciatic nerve contains neuronotrophic activities towards embryonic chick ciliary and sympathetic neurons. The blot and culture technique of Carnow et al. was used to determine if part of the neuronotrophic activities is due to ciliary neuronotrophic factor, which supports the survival of both types of neurons in vitro. The technique involves separating the fluid proteins by SDS-polyacrylamide gel electrophoresis, Western transfer, and then culturing of purified neurons on the nitrocellulose blots. After 24 hr surviving neurons are restricted to regions of the blot where neuronotrophic factor is present. Analysis of 1 and 2 day fluids showed that a multitude of factors are present, particularly in the 19-30 kD molecular weight range, with discrete peaks of activity at molecular weights consistent with those reported for ciliary neuronotrophic factor. There were several other peaks of activity present in the fluids in addition to these.
Article
In the nerve regeneration silicone chamber model, the regenerate which forms across a 10-mm gap between proximal and distal nerve stumps is a monofascicular structure with an outer perineurial-like cell sheath. Recent work has provided indications that the geometry of the regenerate within a silicone chamber can be altered by experimental modifications of the chamber matrix. In the present study we modified the standard silicone chamber into a two-compartment chamber by inserting a 6- or 10-mm-long siliconized nitrocellulose strip in order to obtain two separate regenerates. Light microscopy 16 days after implantation revealed that two separate nerve structures had formed, one on each side of the nitrocellulose partition and adjacent to it, and each with its own perineurial-like cell sheath. In chambers with 6-mm-long strips a monofascicular regenerate started from the proximal stump and divided into two separate structures as it approached the proximal end of the strip: the two fascicles joined again into a monofascicular structure in the distal portion of the chambers. The new two-compartment silicone chamber model appears suitable for future examinations of experimental fasciculation. In addition, the nitrocellulose partition should allow one to study specific effects of growth factors on axonal regeneration in vivo, as growth factors bind strongly to untreated nitrocellulose while retaining their biological activity.
Article
The spatial-temporal progress of peripheral nerve regeneration across a 10-mm gap within a silicone chamber was examined with the light and electron microscope at 2-mm intervals. A coaxial, fibrin matrix was observed at 1 week with a proximal-distal narrowing that extended beyond the midpoint of the chamber. At 2 weeks, Schwann cells, fibroblasts, and endothelial cells had migrated into the matrix from both nerve stumps. There was a delay of 7-14 days after nerve transection and chamber implantation before regenerating axons appeared in the chamber. At 2 weeks, nonmyelinated axons were seen only in the proximal 1-5 mm of the chamber in association with Schwann cells. Axons reached the distal stump by 3 weeks and a proximal-distal gradient of myelination was observed. These observations define the parameters of a morphologic assay for regeneration in this chamber model which can be used to investigate cellular and molecular mechanisms underlying the success of peripheral nerve regeneration.
Article
A new peripheral nerve forms across a 10 mm gap within a silicone chamber regeneration model when the distal segment of a transected sciatic nerve, connected to its end organs, is sutured into the distal end of the chamber. We have tested the ability of other tissue inserts to support axonal regeneration in the chamber. When an isolated 2 mm piece of sciatic nerve was sutured into the distal end, fibrin matrix formation, cell immigration and axonal regeneration were identical to those occurring in the control. When the distal nerve insert was replaced with a 2 mm piece of skin or a ligation, a matrix did not form and subsequent cell immigration and axonal regeneration did not occur. When a 2 mm piece of tendon was inserted, a matrix did form at 1 week, but a structure across the gap was observed at later time periods in only 2 out of 7 chambers. The matrix either dissolved before cells could enter the chamber or did not promote cellular immigration and subsequent axonal regeneration. When the distal end was left open, a matrix formed and cells from the reactive tissue outside the chamber entered the matrix and formed a granulation tissue bridge across the gap. This tissue failed to support axonal regeneration; at 3 weeks, axons stopped 1 mm beyond the proximal stump at the interface with the granulation tissue. Thus, matrix formation and a cellular bridge are necessary but not sufficient to ensure regeneration. Successful regeneration across the silicone chamber gap requires humoral and/or cellular contributions available from peripheral nervous tissue and not from the other tested tissues.
Article
The proximal stump of a transected rat sciatic nerve has been observed to regenerate through a cylindrical silicone chamber across a 10 mm gap to the distal stump. The fluid filling such in vivo chambers contains trophic factors that ensure in vitro survival and growth of at least sensory neurons from rodent dorsal root ganglia--as already demonstrated for fluid generated in vitro from Schwann and other cell cultures.
Article
The range of growth-promoting influences from a distal nerve stump on a regenerating proximal stump was determined using an experimental system in which a gap between cross-anastomosed rat sciatic nerves was encased by a cylindrical silicone chamber. Two arrangements were examined after 1 month in situ: A proximal-distal (PD) system in which both proximal and distal stumps were introduced into the ends of the chamber, and a proximal-open (PO) system in which the distal stump was omitted. When the gap was 6 mm long, a regenerated nerve extended all the way through the chamber in both the PD and PO systems. When the gap was increased to 10 mm, a similar regrowth occurred in the PD chamber, whereas in the PO chamber proximal regrowth was partial or nonexistent. When the gap was increased to 15 mm, no regeneration occurred, even in the presence of the distal stump. These observations confirm that the distal stump influences proximal regeneration and indicate that this influence can act only over a limited distance or volume. Such an influence could consist of humoral agents which support nerve growth and/or outgrowth from the distal stump.
Article
In the present study, the authors reevaluated the temporal course and properties of neurotrophic activities present in the fluid accumulating in the silicone-chamber model for nerve regeneration. The fluid collected from silicone chambers was tested in four different dissociated neuronal cell cultures. Furthermore, the activity of the chamber fluid was examined, using a cell blot technique. There was one major peak of neurotrophic activity and this activity peaked early, about 3 to 6 hr after nerve injury. Results also indicate that the chamber fluid contains at least two types of neurotrophic activities, namely nerve growth factor and ciliary neurotrophic factor.
Article
This paper reviews studies on the basic principles of biostimulation of wound healing by various low-energy lasers. It looks at the mechanism of action of biostimulation as well as the laser's effect on cell proliferation, collagen synthesis, and would healing.
Article
Cytochrome c oxidase is discussed as a possible photoacceptor when cells are irradiated with monochromatic red to near-IR radiation. Four primary action mechanisms are reviewed: changes in the redox properties of the respiratory chain components following photoexcitation of their electronic states, generation of singlet oxygen, localized transient heating of absorbing chromophores, and increased superoxide anion production with subsequent increase in concentration of the product of its dismutation, H2O2. A cascade of reactions connected with alteration in cellular homeostasis parameters (pHi, [Cai], cAMP, Eh, [ATP] and some others) is considered as a photosignal transduction and amplification chain in a cell (secondary mechanisms).
Article
The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. Results: LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.
Article
We have demonstrated that myelination of dorsal root ganglion (DRG) axons occurs in a fully defined, serum-free medium (B27). This implies that there may be components in B27 medium that support myelination. To determine which of the components in B27 were essential for myelination, we systematically removed components from B27 until myelination was lost. We added these components to a fully defined minimal medium (N2) that supports neuron survival but not myelination. When antioxidants were removed from B27, myelination was lost. However, the individual antioxidants did not induce myelination when added to N2 medium. Addition of ascorbic acid along with the B27 antioxidants was sufficient to induce myelination in N2 medium, which was enhanced by retinyl acetate. Removal of vitamin E from B27 caused a partial loss of myelination, and addition of vitamin E to N2 medium containing ascorbic acid induced partial myelination. Addition of serum to the B27 myelinating medium inhibited myelination completely. These results indicate that antioxidants are important for myelination, in vitro. Vitamin E may play an important role. Use of a serum-free medium may be beneficial for in vitro myelination studies because serum has unknown inhibitory effects.
Article
Biological nerve grafts have been extensively utilized in the past to repair peripheral nerve injuries. More recently, the use of synthetic guidance tubes in repairing these injuries has gained in popularity. This review focuses on artificial conduits, nerve regeneration through them, and an account of various synthetic materials that comprise these tubes in experimental animal and clinical trials. It also lists and describes several biomaterial considerations one should regard when designing, developing, and manufacturing potential guidance channel candidates. In the future, it it likely that the most successful synthetic nerve conduit will be one that has been fabricated with some of these strategies in mind.
Article
Posttraumatic nerve repair continues to be a major challenge of restorative medicine. Although enormous progress has been made in surgical techniques over the past three decades, functional recovery after a severe lesion of a major nerve trunk is often incomplete and sometimes unsatisfactory. It is thus particularly important to investigate clinical protocols to enhance nerve regeneration after surgical nerve repair. The present article reviews literature on one possible rehabilitation approach for enhancing nerve recovery, namely phototherapy. The number of experimental studies that have reported on the promoting action of phototherapy on peripheral nerve regeneration, together with the few known side effects related to the use of this type of physical therapy, make it possible to suggest that the time for broader clinical trials has come.
Article
Near-infrared light via light-emitting diode treatment has documented therapeutic effects on neurons functionally inactivated by tetrodotoxin or methanol intoxication. Light-emitting diode pretreatment also reduced potassium cyanide-induced cell death, but the mode of death via the apoptotic or necrotic pathway was unclear. The current study tested our hypothesis that light-emitting diode rescues neurons from apoptotic cell death. Primary neuronal cultures from postnatal rat visual cortex were pretreated with light-emitting diode for 10 min at a total energy density of 30 J/cm2 before exposing to potassium cyanide for 28 h. With 100 or 300 microM potassium cyanide, neurons died mainly via the apoptotic pathway, as confirmed by electron microscopy, Hoechst 33258, single-stranded DNA, Bax, and active caspase-3. In the presence of caspase inhibitor I, the percentage of apoptotic cells in 300microM potassium cyanide was significantly decreased. Light-emitting diode pretreatment reduced apoptosis from 36% to 17.9% (100 microM potassium cyanide) and from 58.9% to 39.6% (300 microM potassium cyanide), representing a 50.3% and 32.8% reduction, respectively. Light-emitting diode pretreatment significantly decreased the expression of caspase-3 elicited by potassium cyanide. It also reversed the potassium cyanide-induced increased expression of Bax and decreased expression of Bcl-2 to control levels. Moreover, light-emitting diode decreased the intensity of 5-(and -6) chloromethy-2', 7-dichlorodihydrofluorescein diacetate acetyl ester, a marker of reactive oxygen species, in neurons exposed to 300 microM potassium cyanide. These results indicate that light-emitting diode pretreatment partially protects neurons against cyanide-induced caspase-mediated apoptosis, most likely by decreasing reactive oxygen species production, down-regulating pro-apoptotic proteins and activating anti-apoptotic proteins, as well as increasing energy metabolism in neurons as reported previously.
Article
Light-emitting diode (LED) photomodulation increases dermal collagen and reduces inflammation. This study evaluated the use of LED photomodulation in the prevention of radiation-induced dermatitis in breast cancer. Patients (n=19) were treated with LED photomodulation (Gentlewaves, Light BioScience, LLC, Virginia Beach, VA) after each of a series of intensity-modulated radiation treatments (IMRT). Skin reactions were monitored weekly with National Cancer Institute (NCI) criteria. Age-matched controls (n=28) received IMRT without LED photomodulation. In LED-treated patients, 18 (94.7%) had grade 0 or 1 reaction and 1 (5.3%) had grade 2 reaction. Among controls, 4 (14.3%) had a grade 1 reaction, 24 (85.7%) had a grade 2 or 3 reaction. One LED-treated patient (5.3%) and 19 controls (67.9%) had to interrupt treatment. LED photomodulation treatments immediately after IMRT reduces the incidence of NCI grades 1, 2, and 3 skin reactions in patients with breast cancer treated by radiation therapy (RT) postlumpectomy.