ArticlePDF Available

Low-Level Laser Therapy Applied Transcranially to Mice following Traumatic Brain Injury Significantly Reduces Long-term Neurological Deficits

Authors:
  • Kaplan Medical Center Rehovot Israel

Abstract and Figures

Low-level laser therapy (LLLT) has been evaluated in this study as a potential therapy for traumatic brain injury (TBI). LLLT has been found to modulate various biological processes. Following TBI in mice, we assessed the hypothesis that LLLT might have a beneficial effect on their neurobehavioral and histological outcome. TBI was induced by a weight-drop device, and motor function was assessed 1 h post-trauma using a neurological severity score (NSS). Mice were then divided into three groups of eight mice each: one control group that received a sham LLLT procedure and was not irradiated; and two groups that received LLLT at two different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser was employed transcranially 4 h post-trauma to illuminate the entire cortex of the brain. Motor function was assessed up to 4 weeks, and lesion volume was measured. There were no significant changes in NSS at 24 and 48 h between the laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS of the laser-treated mice were significantly lower (p < 0.05) than the traumatized control mice that were not treated with the laser. The lesion volume of the laser treated mice was significantly lower (1.4%) than the non-treated group (12.1%). Our data suggest that a non-invasive transcranial application of LLLT given 4 h following TBI provides a significant long-term functional neurological benefit. Further confirmatory trials are warranted.
Content may be subject to copyright.
A preview of the PDF is not available
... The search strategy identified 1784 records, with 1459 remaining after removal of duplicates, leaving 93 full-text articles which were assessed for eligibility against the inclusion/exclusion criteria after abstract screening. Eighteen studies met the criteria for inclusion, with 17 pre-clinical studies being conducted in animal models 38,39,[48][49][50][51][52][53][54][40][41][42][43][44][45][46][47] , and one clinical study using human participants 31 . The full flow chart for search results is shown in the PRISMA diagram in Figure 1. ...
... We identified 17 studies of PBM in animal models of TBI 38,39,[48][49][50][51][52][53][54][40][41][42][43][44][45][46][47] (Table 1) 41 , and one blast-induced neurotrauma (BINT) 40 . ...
... All studies commenced PBM within 8 hours of injury. Ten studies used PBM protocols with a single dose of PBM [38][39][40][41]43,44,[46][47][48]54 , with seven using alternative and additional course durations up to 15 days 53 . ...
Full-text available
Article
Photobiomodulation (PBM) is a therapeutic modality which has gained increasing interest in neuroscience applications, including acute traumatic brain injury (TBI). Its proposed mechanisms for therapeutic effect when delivered to the injured brain include anti-apoptotic and anti-inflammatory effects. This systematic review summarises the available evidence for the value of PBM in improving outcomes in acute TBI and presents a meta-analysis of the pre-clinical evidence for neurological severity score (NSS) and lesion size in animal models of TBI. A systematic review of the literature was performed, with searches and data extraction performed independently in duplicate by two authors. Eighteen published articles were identified for inclusion: seventeen pre-clinical studies of in vivo animal models; and one clinical study in human patients. The available human study supports safety and feasibility of PBM in acute moderate TBI. For pre-clinical studies, meta-analysis for NSS and lesion size were found to favour intervention versus control. Sub-group analysis based on PBM parameter variables for these outcomes was performed. Favourable parameters were identified as: wavelengths in the region of 665 nm and 810 nm; time to first administration of PBM ≤ 4 hours; total number of daily treatments ≤3. No differences were identified between pulsed and continuous wave modes or energy delivery. Mechanistic sub-studies within included in vivo studies are presented and were found to support hypotheses of anti-apoptotic, anti-inflammatory and pro-proliferative effects, and a modulation of cellular metabolism. This systematic review provides substantial meta-analysis evidence of the benefits of PBM on functional and histological outcomes of TBI in in vivo mammalian models. Consideration of study design and PBM parameters should be closely considered for future human clinical studies.
... 8,[18][19][20] There is considerable evidence showing that this method increases brain-derived neurotrophic factor, heals the brain lesions caused by stroke, and improves brain function in mice and rabbits. [21][22][23][24][25] Recent studies support that LLLT decreases neurodegeneration of the hippocampus caused by Ab accumulation. 15 There are also investigations demonstrating that this method affects the cognition abilities of Alzheimer's disease patients and causes improvement of executive performance and enhancement of cerebrovascular blood flow. ...
Article
Objective: To investigate the effects of low-level laser therapy (LLLT) as a new nonpharmaceutical approach to improve cognitive symptoms in patients with dementia. Background: Routine pharmacological treatment of dementia patients is inefficient and has considerable adverse effects. Recent attempts to develop nonpharmaceutical approaches are considered favorable for patients with dementia. Methods: Thirty-two patients with dementia were randomly divided into the same population of LLLT and sham groups. The LLLT group underwent transcranial LLLT, and the sham group received the same protocol with a zero-intensity laser. All patients in the two groups were evaluated using the minimental state examination (MMSE) and clinical dementia rating (CDR) tests at the time of admission as baseline at 2 and 6 weeks postintervention. Results: The rate of change of MMSE scores in sham and LLLT groups was 0.13 ± 0.96 and 2.31 ± 1.81 in week 2 (p = 0.00005) and also -0.25 ± 0.86 and 2.53 ± 1.73 in week 8 (p = 0.000003). In the LLLT group, the mean scores of CDR were 1.28 ± 0.71, 1.28 ± 0.71, and 1.25 ± 0.80 at baseline, week 2, and week 8 (p = 0.605 and p = 0.742), respectively. The mean scores of CDR in the sham group were 1.69 ± 0.73, 1.75 ± 0.68, and 1.72 ± 0.82 at baseline, week 2, and week 8, respectively. Conclusions: These findings suggest that laser therapy could be a promising treatment modality and an adjunct to pharmacotherapy in dementia patients. Clinical Trial Registration: IRCT20191018045148N1 was obtained from the Iranian Registry of Clinical Trials (IRCT.ir).
... It delivered 2 minutes of irradiation using an 808 nm laser 4 hours after the TBI induction. There was a significant improvement in neurofunction and minor loss of cortical tissue in the PBM group compared with the control group (Oron et al., 2007). A different team of researchers investigated the effects of varying wavelengths of laser light (665, 730, 810, 980 nm) on the scalp 4 hours post-TBI. ...
Full-text available
Article
Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy metabolism, and regulation of chronic brain inflammation associated with various conditions, including traumatic brain injury. This scientific overview incorporates the most recent cellular and functional findings in PBM with NIR light in treating neurodegenerative diseases, presents the discussion of the proposed mechanisms of action, and describes the benefits of this treatment in neuroprotection, cell preservation/detoxification, anti-inflammatory properties, and regulation of brain energy metabolism. This review will also discuss the novel aspects and pathophysiological role of the glymphatic and brain lymphatics system in treating neurodegenerative diseases with NIR light stimulations. Scientific evidence presented in this overview will support a combined effort in the scientific community to increase attention to the understudied NIR light area of research as a natural agent in the treatment of neurodegenerative diseases to promote more research and raise awareness of PBM in the treatment of brain disorders.
... A closed-head injury was induced by a weight-drop device. They found that TBI mice treated with laser showed better outcomes in neurobehavioral function (34). Khuman et al. demonstrated that low-level laser light therapy could improve cognitive function in CCI mice (35). ...
Full-text available
Article
Background Photobiomodulation (PBM) using low-level light-emitting diodes (LEDs) can be rapidly applied to various neurological disorders safely and non-invasively.Materials and Methods Forty-eight rats were involved in this study. The traumatic brain injury (TBI) model of rat was set up by a controlled cortical impact (CCI) injury. An 8-channel cortex electrode EEG was fixed to two hemispheres, and gamma oscillations were extracted according to each electrode. A 40 hz blue LED stimulation was set at four points of the frontal and parietal regions for 60 s each, six times per day for 1 week. Modified Neurologic Severity Scores (mNSS) were used to evaluate the level of neurological function.ResultsIn the right-side TBI model, the gamma oscillation decreased in electrodes Fp2, T4, C4, and O2; but significantly increased after 1 week of 40 hz Blue LED intervention. In the left-side TBI model, the gamma oscillation decreased in electrodes Fp1, T3, C3, and O1; and similarly increased after 1 week of 40 hz Blue LED intervention. Both left and right side TBI rats performed significantly better in mNSS after 40 hz Blue LED intervention.ConclusionTBI causes the decrease of gamma oscillations on the injured side of the brain of rats. The 40 hz Blue LED therapy could relieve the gamma oscillation changes caused by TBI and improve the prognosis of TBI.
... Many human studies have demonstrated the potential of transcranial PBM for the augmentation of neurocognitive functions under several conditions (1,(46)(47)(48)(49)(50)(51)(52)(53)(54). Studies using laboratory animals have also documented interesting results of brain PBM (45,55,56). For example, our research group submitted aged rats to PBM with transcranial laser for 58 consecutive days and we noted that laser treatment was able to rejuvenate the spatial mnemonic damage of the aged rats and modulate brain levels of inflammatory markers (56). ...
... Selecting the suitable laser beam parameters is application-dependent and is considered to be crucial for successful outcomes. Several reports have shown the potential of transcranial laser irradiation in treating brain injury and some neurological disorders [2]. ...
Full-text available
Article
The present study aimed at investigating the antidepressant and antioxidant actions of near-infrared (NIR) laser at a wavelength of 830 nm and power of 100 mW which applied transcranially on an animal model of depression induced by repeated doses of reserpine (0.2 mg/kg). Thirty male Wistar adult rats were divided into three groups: rat model of depression; rat model of depression irradiated with laser for 14 days after induction of depression; and the control group that was given the drug vehicle and sham-exposed to the laser. Forced swimming test (FST) was used to verify the induction of animal model of depression and to screen the effect of antidepressant effect of low-level laser at the end of the experiment. Monoamine level, oxidative stress markers, and activities of acetylcholinesterase (AchE) and monoamine oxidase (MAO) were determined in the cortex and hippocampus of the rat brain. Reserpine resulted in depletion of monoamines and elevation in the oxidative stress markers and change in the enzymatic activities measured in both brain areas. Laser irradiation has an inhibitory action on the monoamine oxidase (MAO) in the cortex and hippocampus leading to elevation of the monoamine levels and attenuation of the oxidative stress in the studied areas. FST has emphasized the antidepressant effect of the utilized laser irradiation parameters on the behavioral level. The present findings provide evidence for the antidepressant and antioxidant actions of NIR low-power laser in the rat model of depression. Accordingly, low-laser irradiation may be presented as a potential candidate modality for depression treatment.
Full-text available
Article
Widespread in nature ability of biological objects to emit photons (biophotons) made it possible to create devices for non-invasive and continuous monitoring of the metabolism of organs and tissues, used as a powerful clinical diagnostic tool, as well as for visualisation and spatio-temporal analysis of functioning organs and, in particular, the brain. Numerous experimental data indicating the participation of biophotons in the processes of inter- and intracellular communication served as a theoretical basis for the medical use of low-intensity light therapy for the effective treatment of a wide range of diseases, including delayed wound healing, pain in arthritis, and acute stroke.
Full-text available
Article
This systematic review investigated the repercussions of photobiomodulation using low‐level laser therapy (LLLT) for the treatment of spinal cord injury (SCI) in experimental models. Studies were identified from relevant databases published between January 2009 and December 2021. Nineteen original articles were selected and 68.4% used light at an infrared wavelength. There was a considerable variation of the power used (from 25 to 200 mW), total application time (8 to 3000 seconds) and total energy (0.3 to 450 J). In 79% of the studies, irradiation was initiated immediately after or within two hours of the SCI, and treatment time ranged continuously from five to 21 days. In conclusion, LLLT can be an auxiliary therapy in the treatment of SCI, playing a neuroprotective role, enabling functional recovery, increasing the concentration of nerve connections around the injury site and reducing pro‐inflammatory cytokines. However, there is a need for standardization in the dosimetric parameters. This article is protected by copyright. All rights reserved.
Full-text available
Preprint
A new biomarker is proposed, that shows a diagnostic capability to classify a measure of healthy and unhealthy behaviour by analysing the pattern of brain waves related to discrete frequencies and amplitudes. Discrete frequencies fit in a coherent or in a decoherent frequency pattern and has been substantiated by a quantum physical model about phase-synchronisation of the spectral lines of EEG (Electroencephalography) and MEG (Magnetoencephalography). Phase-synchronisation and spatio-spectral eigenmodes have been shown for our brains and is related to a discrete distribution of energy: En= ħ ωref 2 n+p 3 m. The model shows that the overall resonating spatio-spectral states of living cells and molecules including brain cells can be described by a sum of quantum coherent and decoherent frequencies. Healthy states are quantum coherent and approach a global quantum coherence of 1.0, while unhealthy states are decoherent and cause a decrease of coherence. The proposed model of spatio-spectral eigenmodes has been substantiated by analysing the many measured frequency patterns of EEG's and MEG's, and electromagnetic exposures of brain cells, glands and neurons. The EEG-and MEG studies of healthy persons show a global quantum coherence of 0.90-1.00. Unhealthy subjects show a decrease of coherence, and an increase of decoherence. ADHD subjects show a decrease of coherence from 1.0 to 0.83. During epileptic seizure, the coherence of participants is reduced from 0.94 to 0.75. Depressed patients have a lower coherence than healthy persons: 0.77-0.88, autistic persons show a lower coherence of 0.50 till 0.75, patients with severe psychiatric disorders show a coherence of about 0.59, and participants during anaesthesia show a level of 0.25. Repetitive transcranial magnetic stimulation (rTMS) has been reported to modify brain oscillations and the periodic electromagnetic force generated during rTMS can result in local entrainment of biologically relevant rhythms, mimicking frequency specific oscillatory activities. Potential differential effects occur at typical frequencies: 0.50, 0.75, 1, 5, 6, 8, 9, 10, 12, 15, 17, 20, 25, 40 Hz, that are equal or approach the proposed algorithm, and fit with the eigenstates (eigenfrequencies) described by the proposed equation of coherence. The coherent and decoherent (chaos-like) frequencies can be aligned at a frequency scale and are arranged according to an alternating ordering positioned at a toroidal geometry, while transition frequencies are located just in between the coherent and decoherent frequency zones. The overall results show a presence of an informational quantum code and a molecular code-script, which supplies information to realize biological order in life cells and substantiates a collective Bose-Einstein type of behaviour. Typical nano/submicron minerals can copy healthy behaviour of living cells.
Full-text available
Article
Background: Several studies have detailed the efficacy of Photobiomodulation Therapy (PBMT) as a treatment for concussions [1]. As there are no widely accepted imaging or laboratory modalities that document concussive injuries, monitoring improvement objectively proves difficult. ImPACT® is a computer based neurocognitive assessment tool meant to measure cognitive performance and subjective symptoms for concussion injuries. This study uses ImPACT® as a means to document an improvement in symptomatology for patients with persistent post-concussion symptoms pre and posttreatment with PBMT [2]. Methods: This retrospective study reviews patient performance in the ImPACT® test in a cohort of 35 patients who are diagnosed with mild Traumatic Brain Injuries (mTBI) and experiencing persistent post-concussive symptoms. Patients initially took the Post Injury 1 test then underwent PBMT therapy using the BIOFLEX DUO+ system three times a week for 4 weeks using approved parameters for treatment of the cervical spine soft tissue injuries. After the 4 week treatment, patients took the Post Injury 2 test and the results were compared. Results: All patients improved clinically after PBMT and their Post injury 2 ImPACT® test results were significantly better compared to their Post injury 1 ImPACT® test results. Conclusion: PBMT may provide neurological rehabilitation in patients with persistent postconcussion symptoms and ImPACT® is an appropriate and objective measure to monitor and assess improvement.
Full-text available
Article
This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased ATP important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is non-invasive, painless, and non-thermal (FDA-cleared, non-significant risk device). Eleven chronic, mTBI participants (26-62 Yr, 6M) with non-penetrating head injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (MWF, 6 Wks), starting at 10 Mo to 8 Yr post- mTBI (MVA or sports-related; and one participant, IED blast injury). Four had a history of multiple concussions. Each LED cluster head (2.1" diameter, 500mW, 22.2mW/cm2) was applied for 10 min to each of 11 scalp placements (13 J/cm2). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre- LED, and at 1 Wk, 1 and 2 Mo post- the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for Stroop test for Executive Function, Trial 3 inhibition (p=.004); Stroop, Trial 4 inhibition switching (p=.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=.003); and CVLT-II, Long Delay Free Recall (p=.006). Participants reported improved sleep, and fewer PTSD symptoms, if present. Participants and family reported better ability to perform social, interpersonal and occupational functions. These open-protocol data suggest placebo controlled studies are warranted.
Full-text available
Article
Previous work has demonstrated the efficacy of irradiating tissue with red to infrared light in mitigating cerebral pathology and degeneration in animal models of stroke, traumatic brain injury, parkinsonism and Alzheimer's disease (AD). Using mouse models, we explored the neuroprotective effect of near infrared light (NIr) treatment, delivered at an age when substantial pathology is already present in the cerebral cortex. We studied two mouse models with AD-related pathologies: the K369I tau transgenic model (K3), engineered to develop neurofibrillary tangles, and the APPswe/PSEN1dE9 transgenic model (APP/PS1), engineered to develop amyloid plaques. Mice were treated with NIr 20 times over a four-week period and histochemistry was used to quantify AD-related pathological hallmarks and other markers of cell damage in the neocortex and hippocampus. In the K3 mice, NIr treatment was associated with a reduction in hyperphosphorylated tau, neurofibrillary tangles and oxidative stress markers (4-hydroxynonenal and 8-hydroxy-2[prime]-deoxyguanosine) to near wildtype levels in the neocortex and hippocampus, and with a restoration of expression of the mitochondrial marker cytochrome c oxidase in surviving neurons. In the APP/PS1 mice, NIr treatment was associated with a reduction in the size and number of amyloid-beta plaques in the neocortex and hippocampus. Our results, in two transgenic mouse models, suggest that NIr may have potential as an effective, minimally-invasive intervention for mitigating, and even reversing, progressive cerebral degenerations.
Full-text available
Article
Near-infrared low-level laser (NIR-LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR-LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS). TLS was applied for 5 minutes over the representation of the right first dorsal interosseal muscle (FDI) in left primary motor cortex (M1), in 14 healthy subjects. Motor evoked potentials (MEPs) from the FDI, elicited by single-pulse TMS, were measured at baseline and up to 30 minutes after the TLS. The average MEP size was significantly reduced during the first 20 minutes following the TLS. The pattern was present in 10 (71.5%) of the participants. The MEP size reduction correlated negatively with the motor threshold at rest. TLS with NIR-LLL induced transitory reduction of the excitability of the stimulated cortex. These findings give further insights into the mechanisms of TLS effects in the human cerebral cortex, paving the way for potential applications of TLS in treatment of stroke and in other clinical settings. Lasers Surg. Med. © 2013 Wiley Periodicals, Inc.
Full-text available
Article
Traumatic injury to the central nervous system results in damage to tissue beyond the primary injury, termed secondary degeneration. Key events thought to be associated with secondary degeneration involve aspects of mitochondrial function which may be modulated by red/near-infrared irradiation therapy (R/NIR-IT), but precisely how mitochondria are affected in vivo has not been investigated. Secondary degeneration was modelled by transecting the dorsal aspect of the optic nerve in adult rats and mitochondrial ultrastructure in intact ventral optic nerve vulnerable to secondary degeneration investigated with transmission electron microscopy. Despite reported increases in fission following central nervous system injury, we saw no change in mitochondrial densities in optic nerve vulnerable to secondary degeneration in vivo. However, in axons, frequency distributions of mitochondrial profile areas showed higher cumulative probabilities of smaller mitochondrial profiles at day 1 after injury. Glial mitochondrial profiles did not exhibit changes in area, but a more elliptical mitochondrial shape was observed at both day 1 and 7 following injury. Importantly, mitochondrial autophagic profiles were observed at days 1 and 7 in optic nerve vulnerable to secondary degeneration in vivo. Citrate synthase activity was used as an additional measure of mitochondrial mass in ventral optic nerve and was decreased at day 7, whereas mitochondrial aconitase activity increased at day 1 and day 28 after injury in optic nerve vulnerable to secondary degeneration. R/NIR-IT has been used to treat the injured central nervous system, with reported improvements in oxidative metabolism suggesting mitochondrial involvement, but ultrastructural information is lacking. Here we show that R/NIR-IT of injured animals resulted in distributions of mitochondrial areas and shape not significantly different from control and significantly reduced mitochondrial autophagic profiles. R/NIR-IT also resulted in decreased citrate synthase activity (day 7) and increased aconitase activity (day 1) in optic nerve vulnerable to secondary degeneration. These findings suggest that mitochondrial structure and activity of enzymes of the citric acid cycle are dynamically altered during secondary degeneration in vivo and R/NIR-IT may protect mitochondrial structure.
Article
Low energy laser irradiation (LELI) has been shown to promote skeletal muscle cell activation and proliferation in primary cultures of satellite cells as well as in myogenic cell lines. Here, we have extended these studies to isolated myofibers. These constitute the minimum viable functional unit of the skeletal muscle, thus providing a close model of in vivo regeneration of muscle tissue. We show that LELI stimulates cell cycle entry and the accumulation of satellite cells around isolated single fibers grown under serum-free conditions and that these effects act synergistically with the addition of serum. Moreover, for the first time we show that LELI promotes the survival of fibers and their adjacent cells, as well as cultured myogenic cells, under serum-free conditions that normally lead to apoptosis. In both systems, expression of the anti-apoptotic protein Bcl-2 was markedly increased, whereas expression of the pro-apoptotic protein BAX was reduced. In culture, these changes were accompanied by a reduction in the expression of p53 and the cyclin-dependent kinase inhibitor p21, reflecting the small decrease in viable cells 24 hours after irradiation. These findings implicate regulation of these factors as part of the protective role of LELI against apoptosis. Taken together, our findings are of critical importance in attempts to improve muscle regeneration following injury.
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 lasers effect on cell proliferation, collagen synthesis, and would healing.
Article
We have previously shown near infrared light (NIr), directed transcranially, mitigates loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuroprotective by administering different MPTP doses (50, 75, 100 mg/kg) to mice and treating with 670 nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50 mg/kg (∼30% increase vs sham-treated MPTP mice, p<0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (∼50% increase vs sham-treated MPTP mice, p<0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over transcranial irradiation.
Article
Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8 ± 3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6 ± 2.9 %. MTT reduction rate was reduced to 75.9 ± 2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6 ± 4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9 ± 4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6 ± 13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.
Article
Excitotoxicity describes a pathogenic process whereby death of neurons releases large amounts of the excitatory neurotransmitter glutamate, which then proceeds to activate a set of glutamatergic receptors on neighboring neurons (glutamate, N-methyl-D-aspartate (NMDA), and kainate), opening ion channels leading to an influx of calcium ions producing mitochondrial dysfunction and cell death. Excitotoxicity contributes to brain damage after stroke, traumatic brain injury, and neurodegenerative diseases, and is also involved in spinal cord injury. We tested whether low level laser (light) therapy (LLLT) at 810 nm could protect primary murine cultured cortical neurons against excitotoxicity in vitro produced by addition of glutamate, NMDA or kainate. Although the prevention of cell death was modest but significant, LLLT (3 J/cm(2) delivered at 25 mW/cm(2) over 2 min) gave highly significant benefits in increasing ATP, raising mitochondrial membrane potential, reducing intracellular calcium concentrations, reducing oxidative stress and reducing nitric oxide. The action of LLLT in abrogating excitotoxicity may play a role in explaining its beneficial effects in diverse central nervous system pathologies. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).