Acta Cirurgica Brasileira
On-line version ISSN 1678-2674
Acta Cir. Bras. vol.30 no.9 São Paulo Sep. 2015
http://dx.doi.org/10.1590/S0102-865020150090000005
ORIGINAL ARTICLES
The influence of low-level laser irradiation on spinal cord injuries following ischemia- reperfusion in rats1
Amir Sotoudeh I , Amirali Jahanshahi II , Saeed Zareiy III , Mohammad Darvishi IV , Nasim Roodbari V , Ali Bazzazan VI
IAssistant Professor, Faculty of Veterinary Science, Kahnooj Branch, Islamic Azad University (IAU), Kerman, Iran. Design, analysis and interpretation of data; manuscript writing
IIResearcher, Elite Club, Kahnooj Branch, IAU, Kerman, Iran. Design and acquisition of data
IIIResident, Aerospace and Subaquatic Medicine School, AJA University of Medical Sciences, Tehran, Iran Branch, and Islamic Azad University, Tehran, Iran. Technical procedures, acquisition and interpretation of data
IVAssociate Professor, Department of Infection Medicine, AJA University of Medical Sciences, Tehran, Iran. Analysis and interpretation of data, statistical analysis
VAssistant Professor, Faculty of Experimental Science, Kahnooj Branch, Islamic Azad University, Kerman, Iran. Analysis of data, manuscript writing
VIGraduate student, Faculty of Veterinary Science, Garmsar Branch, IAU, Semnan, Iran. Acquisition and interpretation of data.
ABSTRACT
PURPOSE:
To investigate if low level laser therapy (LLLT) can decrease spinal cord injuries after temporary induced spinal cord ischemia-reperfusion in rats because of its anti-inflammatory effects.
METHODS:
Forty eight rats were randomized into two study groups of 24 rats each. In group I, ischemic-reperfusion (I-R) injury was induced without any treatment. Group II, was irradiated four times about 20 minutes for the following three days. The lesion site directly was irradiated transcutaneously to the spinal direction with 810 nm diode laser with output power of 150 mW. Functional recovery, immunohistochemical and histopathological changes were assessed.
RESULTS:
The average functional recovery scores of group II were significantly higher than that the score of group I (2.86 ± 0.68, vs 1.38 ± 0.09; p<0.05). Histopathologic evaluations in group II were showed a mild changes in compare with group I, that suggested this group survived from I-R consequences. Moreover, as seen from TUNEL results, LLLT also protected neurons from I-R-induced apoptosis in rats.
CONCLUSION:
Low level laser therapy was be able to minimize the damage to the rat spinal cord of reperfusion-induced injury.
INTRODUCTION
Neurologic injuries due to I-R of the spinal cord has an incidence of between 2.9% and 23%1. Pathogenic mechanisms of neuronal cell death after spinal cord I-R injury include energy failure, excitotoxicity, and oxidative stress2 , 3.There are some applications which can reduce spinal cord I-R injuries such as hypothermia, vascular shunting, left heart bypass, drainage of cerebrospinal fluid, monitoring of somatosensory evoked potentials, single clamp technique and reimplantation of major intercostal arteries4 – 6. Also, there are experimental studies like ischemic preconditioning and adjunctive medications for reducing the incidence of this complication7. Despite several surgical modifications and pharmacologic approaches, postoperative spinal cord dysfunction has not been totally eliminated8.
Low level laser therapy (LLLT) has photochemical reactions with cell membranes, cellular organelles and enzymes. LLLT can induce a complex chain of physiological reactions by increasing mitochondrial respiration, activating transcription factors, reducing key inflammatory mediators, inhibiting apoptosis, stimulating angiogenesis, and increasing neurogenesis to enhance wound healing, tissue regeneration and reduce acute inflammation9 , 10. LLLT has been clinically applied to treatment of rheumatoid arthritis, periodontal disease, pain management and healing of wounds and burns11 – 13. Many studies approved that LLLT has the potential to be an effective noninvasive therapy for spinal cord injury14 , 15.
The aim of this study is to evaluate if LLLT can protect rats spinal cord from I-R injury, so we hypothesized that LLLT would attenuate immunohistochemical and histopathological changes and improve functional recovery after the ischemia/ reperfusion-induced spinal cord injury in rats.
METHODS
Animal care and experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH publications No. 8023). Forty eight male Wistar rats weighing 400-450g were used in this study. Anesthesia was induced by intramuscular injection of ketamine hydrochloride 60 mg/kg and xylazine 10 mg/kg. A longitudinal incision was made through the skin on the abdominal region and the abdominal aorta was exposed through midline laparotomy. Heparin (250 UI/kg) was administered intravenously before aortic clamping. Spinal cord ischemia was induced by crossclamping for 60 min, using Bulldog forceps (Figure 1).
Vascular clamps were placed under the left renal vein and above the bifurcation in the aorta. Then the forceps were removed and the chest closed routinely. Animals were placed in their cages after recovery. Rats were randomly assigned to two groups.
FIGURE 1 Surgical site: the ventral aorta was exposed and clamped by Bulldog forceps for 60 minutes.
In control group (group I), I-R injury was induced but not irradiated with the laser beam. The irradiation protocol was applied as Byrnes described previously16. Briefly in treatment group (group II), 15 minutes after I-R induction on the spinal cord, the lesion site as a rectangular, about 3 cm2(3 cm length×1 cm width) was irradiated transcutaneously to the spinal direction with 810 nm diode laser (Thor International, UK;) with output power of 150 mW. The dosage applied to the surface of the skin was 1,589 J/cm2 per day (0.53 W/cm2, 450 J). Irradiation was repeated daily for the following 3 consecutive days. In each day, irradiation was applied 4 times about 20 minutes with contact mode.
Neurologic scoring system
The Neurologic deficits of animals were evaluated on postoperative 72 hour by a single trained blinded observer by using the following scoring:
Grade 0: paraplegia with no lower extremity motor function;
Grade 1: poor lower extremity motor function;
Grade 2: good movement of the hind limbs, but unable to stand;
Grade 3: able to stand but unable to walk normally; Grade 4: complete recovery17.
Spinal cord histopathologic examination
All animals were anesthetized with lethal dose of pentobarbital (25 mg/kg). Spinal cords were dissected totally and fixed in 10% formalin and embedded in paraffin with routine procedures. Sections from fourth to sixth lumbar segment were obtained. The spinal cord tissues were embedded in paraffin and serial transverse sections (5 µm) cut from paraffin blocks and stained with hemotoxylin and eosin for histopathologic examination. Histopathologic evaluations were performed with means of light microscopy by a neuropathologist who was blinded to experimental conditions.
TUNEL staining
TUNEL staining was performed by an in situ cell death detection kit (Roche, Germany). Hematoxylin was used to counterstain the sections. Quantitative analysis was performed blindly by counting the number of TUNEL positive neurons in the ventral horns in five microscopic fields as described previously18.
Statistical analysis
All data are expressed as mean ± standard deviation. Statistical analysis of the neurologic scores were analyzed by using KruskalWallis one-way analysis of variance (ANOVA). The investigators were blinded to the treatments. Values for statistical analyses were considered significant at p<0.05. All analyses were performed by using the SPSS software package (SPSS, Inc, Chicago, Ill).
RESULTS
Neurological evaluations presented in Table 1. In the group I, the neurological scores was lower. Although in the group II, the Tarlov scale increased and showed a significant difference after 72h of reperfusion (p<0.05).
TABLE 1 – Neurologic status 72 hours after reperfusion as evaluated by the modified Tarlov neurologic recovery scale.
score
Group I (Control) N=24
Group II (Treatment) N=24
0
8
1
1
7
3
2
3
5
3
4
4
4
2
11
Mean ± SD
1.38 ± 0.09
2.86 ± 0.68*
*Mean neurologic scores showed a significant difference between control and treatment groups (p<0.05) both at 72h after reperfusion.
Histopathologic evaluations in group I, presented that had severe ischemic injury with inclusive necrosis of gray matter, which enclosed typically necrotic nuroglia cells with eosinophilic cytoplasm, and loss of cytoplasmic structures. In addition the numbers of normal nuroglia cells were apparently reduced in this group and neuronal structural alterations were observed, which included oligodendrocytes pyknosis, light staining tigroid body, nucleus’s atrophy of nuroglia cell and nucleolus disappearance of oligodendrocytes. Furthermore, hemorrhagic macules were scattered into tissue structures and vacuolar changes were observed in the cytoplasm (Figure 2). The histopathologic changes in group II were milder than that observed in the group I, and the gray matter architecture was generally preserved, with most nuroglia cells appearing to have survived the ischemic consequences (Figure 3).
FIGURE 2 The neurons of spinal cord anterior horn of group I were assessed by H&E staining and viewed at the magnification of 200 times which presented group necrotic changes with prominent vacuolization, intensely eosinophilic cytoplasm, Nissl granule loss, and pyknosis (arrows) as well as by the presence of infiltrating neutrophils and mononuclear phagocytes severe percellular edema and glial cell proliferation.
FIGURE 3 The neurons of spinal cord anterior horn of group II were assessed by H&E staining and viewed at the magnification of 200 times which showed relative preservation of tissue architecture along with almost complete protection of the neurons, vascular structures, and glial cells along with only mild per cellular edema. The arrows indicate ischemia neuron cells showing mildly eosinophilic cytoplasm, Nissl body loss, and pyknosis.
Average TUNEL-positive cell counts are shown in Table 2. These data show that the group II exhibited significantly fewer TUNEL-positive cells compared with the group I.
TABLE 2 – Quantitative analysis of the number of TUNEL-positive cells in the ventral horn of spinal cord of all groups, 72h after reperfusion.
Group
I (Control)
II (Treatment)
Number of TUNEL-posetive motor neurons
Mean SD (n=24) 73.04 0.3
Mean SD (n=24) 36.50** 0.6
*Mean Quantitative analysis showed a significant difference between control and treatment groups (p<0.05) both at 72h after reperfusion.
It is understandable that the number of TUNEL-positive neurons decreased significantly after laser therapy, suggesting that LLLT may protect spinal cords from I-R apoptosis. Spinal cord sections were stained with TUNEL and observed at the light microscopic level (400 times magnification). In the spinal cord ventral horn of the group I, amount of vacuoles appeared and numerous TUNEL-positive neurons were observed (Figure 4). By contrary, very few positively stained neurons were observed in group II (Figure 5).
FIGURE 4 TUNEL staining and quantification of apoptotic motor neurons after reperfusion (×400). Many TUNEL-positive neurons with intense nucleus staining were visible in group I. The arrows indicate TUNEL-positive motor neurons.
FIGURE 5 TUNEL staining and quantification of apoptotic motor neurons after reperfusion (×400). Only a small number of positively stained neurons were observed in the group II. The arrows TUNELpositive motor neurons.
DISCUSSION
Our results showed that LLLT will be able to reduce the damages of spinal cord after I-R in rats. This result was verified by both neurological and histological and observations. Additionally, Functional recovery of LLLT group was significantly improved when compared with control group.
Spinal cord I-R injury is a persistent clinical problem in surgical repair of thoracic and thoracoabdominal aneurism surgeries19 , 20. The major cause of spinal cord injury, during and after aortic surgery to the occurrence of one or more of the three following events: (I) the duration and degree of ischaemia; (II) failure to re-establish blood flow to the spinal cord after repair; (III) a biochemically mediated reperfusion injury21. Reperfusion is the restoration of blood flow to the organ after a period of ischaemia. Reperfusion of ischaemic neuronal tissues leads to release production of oxygen derived free radicals, produced as a result of incomplete oxygenation during the period of ischaemia22. Inflammatory response with production of cytokines by microglia and activated neutrophils also contributes to generation of these radicals23 , 24. Several different surgical strategies and laboratory studies have been developed in attempt to decrease the risk of this devastating complication25 – 27. However, neurological injury in thoracoabdomial surgery remains one of the greatest unsolved mysteries28 – 30.
The therapeutic effects of LLLT have been reported, being associated with production of anti-apoptotic, pro-proliferative, antioxidant, and angiogenic factors31 – 33. LLLT also known as photobiomodulation, is an emerging therapeutic approach in which cells or tissues are exposed to low-levels of red and near-IR light. Its experimental applications have broadened to include serious diseases such as heart attack, stroke, and spinal cord injury. Oron et al, suggested that a transcranial application of LLLT after traumatic brain injury provides a significant long-term functional neurological benefit and decreases brain tissue loss34. In another research applied LLLT in acute Spinal cord injury caused by of trauma which promotes axonal regeneration and functional recovery35.
LLLT may have beneficial effects in the acute treatment of I-R by reducing inflammatory mediators, inhibiting apoptosis, stimulating angiogenesis, and increasing neurogenesis9. Transcranial LLLT applied after ischemic stroke in rats caused a significant improvement of neurological score compared to sham animals36.
We hypothesized that LLLT would effectively protect spinal cord by its antioxidant and anti-inflammatory. To our knowledge, the present study probably is the first study to evaluating the neuroprotective effects of LLLT in attenuating I-R induced neurologic injury to the rat spinal cord. It is known that functional recovery after I-R is highly correlated with the volume of remaining normal nerve fibers in spinal tissue37. Adno et al.11, demonstrated transcutaneous application of 810-nm nonpolarized laser significantly promoted axonal regrowth, our results are in agreement with that and show association of improved neurologic status.
Byrnes et al.16, found that 810 nm light, at a dosage of 1.589 J/cm2, significantly improves axonal regrowth, functional improvement and statistically significant suppression of immune cell invasion and pro-inflammatory cytokine and chemokine gene expression. Similarly we documented that LLLT had efficient protection on neural cells from apoptosis or necrosis. Also decreased inflammatory cell accumulation in the spinal cords of animals that received LLLT as compared with the control group also supports LLLT proposed anti-inflammatory property and may contribute to neuroprotection.
CONCLUSION
Low level laser therapy protects the spinal cord from ischemia-reperfusion injury spinal cord ischemia and provide better locomotor function in rats which may be related to antiinflammatory properties of that.
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Financial source: Islamic Azad University
1Research performed at Department of Surgery, Faculty of Veterinary, Islamic Azad University (IAU), Kahnooj Branch.
Received: May 06, 2015; Revised: July 07, 2015; Accepted: August 04, 2015
Correspondence:Amir Sotoudeh Islamic Azad University Kahnooj Branch Kahnooj, Iran Phone: 00989121768066 Fax: 00983495230203 dramirsotoudeh@kahnoojiau.ac.ir
Conflict of interest: none
This is an open-access article distributed under the terms of the Creative Commons Attribution License
Neurophotonics. 2016 Jul;3(3):031404. doi: 10.1117/1.NPh.3.3.031404. Epub 2016 Mar 4
Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.
Cassano P1, Petrie SR2, Hamblin MR3, Henderson TA4, Iosifescu DV5.
Author information
1Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Psychiatry, 401 Park Drive, Boston, Massachusetts 02215, United States.
2Massachusetts General Hospital, Depression Clinical and Research Program, One Bowdoin Square, 6th Floor, Boston, Massachusetts 02114, United States.
3Massachusetts General Hospital, Wellman Center for Photomedicine, 50 Blossom Street, Boston, Massachusetts 02114, United States; Harvard Medical School, Department of Dermatology, 55 Fruit Street, Boston, Massachusetts 02114, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
4Synaptic Space, 3979 East Arapahoe Road, Littleton, Colorado 80122, United States; Neuro-Laser Foundation, Suite 420, 215 South Wadsworth, Lakewood, Colorado 80226, United States.
5Mount Sinai Medical School, Mood and Anxiety Disorders Program, 1428 Madison Avenue, New York, New York 10029, United States; Mount Sinai Medical School, Department of Psychiatry and Neuroscience, 1 Gustave L. Levy Place, New York, New York 10029, United States.
Abstract
We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: “near-infrared radiation,” “NIR,” “low-level light therapy,” “low-level laser therapy,” or “LLLT” plus “depression.” We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.
J Exp Neurosci. 2016 Feb 1;10:1-19. doi: 10.4137/JEN.S33444. eCollection 2016.
Neuroprotective Effects Against POCD by Photobiomodulation: Evidence from Assembly/Disassembly of the Cytoskeleton.
Liebert AD1, Chow RT2, Bicknell BT3, Varigos E4.
Author information
1University of Sydney, Sydney, NSW, Australia.
2Brain and Mind Institute, University of Sydney, Sydney, NSW, Australia.
3Australian Catholic University, Sydney, NSW, Australia.
4Olympic Park Clinic, Melbourne, VIC, Australia.
Abstract
Postoperative cognitive dysfunction (POCD) is a decline in memory following anaesthesia and surgery in elderly patients. While often reversible, it consumes medical resources, compromises patient well-being, and possibly accelerates progression into Alzheimer’s disease. Anesthetics have been implicated in POCD, as has neuroinflammation, as indicated by cytokine inflammatory markers. Photobiomodulation (PBM) is an effective treatment for a number of conditions, including inflammation. PBM also has a direct effect on microtubule disassembly in neurons with the formation of small, reversible varicosities, which cause neural blockade and alleviation of pain symptoms. This mimics endogenously formed varicosities that are neuroprotective against damage, toxins, and the formation of larger, destructive varicosities and focal swellings. It is proposed that PBM may be effective as a preconditioning treatment against POCD; similar to the PBM treatment, protective and abscopal effects that have been demonstrated in experimental models of macular degeneration, neurological, and cardiac conditions.
J Neurosurg. 2015 Nov 27:1-13. [Epub ahead of print]
Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.
Reinhart F1, Massri NE2, Chabrol C1, Cretallaz C1, Johnstone DM3, Torres N1, Darlot F1, Costecalde T1, Stone J3, Mitrofanis J2, Benabid AL1, Moro C1.
Author information
1CEA, Leti, and Clinatec Departments, University Grenoble Alpes, Minatec Campus, Grenoble, France; and
2Departments of 2 Anatomy and.
3Physiology, University of Sydney, New South Wales, Australia.
Abstract
OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson’s disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective.
METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis.
RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other “symptomatic” elements contributing to behavioral improvements in these rats.
CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats.
J Cereb Blood Flow Metab. 2014 Aug;34(8):1391-401. doi: 10.1038/jcbfm.2014.95. Epub 2014 May 21.
Low-level laser therapy effectively prevents secondary brain injury induced by immediate early responsive gene X-1 deficiency.
Zhang Q1, Zhou C1, Hamblin MR2, Wu MX2.
Author information
11] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
21] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA [3] Affiliated faculty member of the Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
Abstract
A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1? and IL-6 but upregulated TNF-?. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.
J Biomed Opt. 2013;18(12):128005. doi: 10.1117/1.JBO.18.12.128005.
Near-infrared stimulation on globus pallidus and subthalamus.
Yoo M1, Koo H2, Kim M2, Kim HI3, Kim S4.
1Gwangju Institute of Science and Technology (GIST), Department of Medical System Engineering, Gwangju, Republic of Korea.
2Wonkwang University School of Medicine, Department of Physiology, Iksan, Republic of Korea.
3Gwangju Institute of Science and Technology (GIST), Department of Medical System Engineering, Gwangju, Republic of KoreacGwangju Institute of Science and Technology (GIST), School of Mechatronics, Gwangju, Republic of KoreadPresbyterian Medical Center, Department of Neurosurgery, Jeonju, Republic of Korea.
4Gwangju Institute of Science and Technology (GIST), Department of Medical System Engineering, Gwangju, Republic of KoreacGwangju Institute of Science and Technology (GIST), School of Mechatronics, Gwangju, Republic of Korea.
Abstract
Near-infrared stimulation (NIS) is an emerging technique used to evoke action potentials in nervous systems. Its efficacy of evoking action potentials has been demonstrated in different nerve tissues. However, few studies have been performed using NIS to stimulate the deep brain structures, such as globus pallidus (GP) and subthalamic nucleus (STN). Male Sprague-Dawley rats were randomly divided into GP stimulation group (n=11) and STN stimulation group (n=6). After introducing optrodes stereotaxically into the GP or STN, we stimulated neural tissue for 2 min with continuous near-infrared light of 808 nm while varying the radiant exposure from 40 to 10 mW. The effects were investigated with extracellular recordings and the temperature rises at the stimulation site were also measured. NIS was found to elicit excitatory responses in eight out of 11 cases (73%) and inhibitory responses in three cases in the GP stimulation group, whereas it predominantly evoked inhibitory responses in seven out of eight cases (87.5%) and an excitatory response in one case in STN stimulation group. Only radiation above 20 mW, accompanying temperature increases of more than 2°C, elicited a statistically significant neural response (p<0.05). The responsiveness to NIS was linearly dependent on the power of radiation exposure.
J Neurotrauma. 2014 Jun 1;31(11):1008-17. doi: 10.1089/neu.2013.3244. Epub 2014 May 8.
Significant improvements in cognitive performance post-transcranial, red/near-infrared light-emitting diode treatments in chronic, mild traumatic brain injury: open-protocol study.
Naeser MA1, Zafonte R, Krengel MH, Martin PI, Frazier J, Hamblin MR, Knight JA, Meehan WP 3rd, Baker EH.
Author information
11 VA Boston Healthcare System , Boston, Massachusetts.
Abstract
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 adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). 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 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.
Lasers Med Sci. 2014 May 24. [Epub ahead of print]
“Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury”
Paula AA1, Nicolau RA, Lima MD, Salgado MA, Cogo JC.
1Instituto de Pesquisa e Desenvolvimento (IP&D), Universidade do Vale do Paraíba (Univap), São José dos Campos, São Paulo, Brazil.
Abstract
Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n?=?3), control surgery (n?=?3), laser 6 h after surgery (n?=?5), laser 48 h after surgery (n?=?5), medullar lesion (n?=?5) without phototherapy, medullar lesion?+?laser 6 h after surgery (n?=?5), and medullar lesion?+?laser 48 h after surgery (n?=?5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.
J Cereb Blood Flow Metab. 2014 May 21. doi: 10.1038/jcbfm.2014.95. [Epub ahead of print]
Low-level laser therapy effectively prevents secondary brain injury induced by immediate early responsive gene X-1 deficiency.
Zhang Q1, Zhou C1, Hamblin MR2, Wu MX2.
Author information
11] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
21] Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA [3] Affiliated faculty member of the Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
Abstract
A mild insult to the brain can sometimes trigger secondary brain injury, causing severe postconcussion syndrome, but the underlying mechanism is ill understood. We show here that secondary brain injury occurs consistently in mice lacking immediate early responsive gene X-1 (IEX-1), after a gentle impact to the head, which closely simulates mild traumatic brain injury in humans. The pathologic lesion was characterized by extensive cell death, widespread leukocyte infiltrates, and severe tissue loss. On the contrary, a similar insult did not induce any secondary injury in wild-type mice. Strikingly, noninvasive exposure of the injured head to a low-level laser at 4 hours after injury almost completely prevented the secondary brain injury in IEX-1 knockout mice. The low-level laser therapy (LLLT) suppressed proinflammatory cytokine expression like interleukin (IL)-1? and IL-6 but upregulated TNF-?. Moreover, although lack of IEX-1 compromised ATP synthesis, LLLT elevated its production in injured brain. The protective effect of LLLT may be ascribed to enhanced ATP production and selective modulation of proinflammatory mediators. This new closed head injury model provides an excellent tool to investigate the pathogenesis of secondary brain injury as well as the mechanism underlying the beneficial effect of LLLT.Journal of Cerebral Blood Flow & Metabolism advance online publication, 21 May 2014; doi:10.1038/jcbfm.2014.95.
Alzheimers Res Ther. 2014; 6(1): 2.
Published online Jan 3, 2014. doi: 10.1186/alzrt232
Photobiomodulation with near infrared light mitigates Alzheimer’s disease- related pathology in cerebral cortex – evidence from two transgenic mouse models.
Sivaraman Purushothuman,1,2 Daniel M Johnstone,1,2 Charith Nandasena,1,2 John Mitrofanis,1,3 and Jonathan Stone1,2
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