Traumatic Brain Injury

Photomed Laser Surg. 2016 Dec;34(12):610-626. doi: 10.1089/pho.2015.4037.

Transcranial, Red/Near-Infrared Light-Emitting Diode Therapy to Improve Cognition in Chronic Traumatic Brain Injury.

Naeser MA1,2, Martin PI1,2, Ho MD1,2, Krengel MH1,2, Bogdanova Y1,3, Knight JA1,3,4, Yee MK1,2, Zafonte R5,6,7,8, Frazier J9, Hamblin MR10,11,12, Koo BB13.

Author information

  • 11 VA Boston Healthcare System (12-A) , Boston, Massachusetts.
  • 22 Department of Neurology, Boston University School of Medicine , Boston, Massachusetts.
  • 33 Department of Psychiatry, Boston University School of Medicine , Boston, Massachusetts.
  • 44 Behavioral Sciences Division, National Center for PTSD, VA Boston Healthcare System , Boston, Massachusetts.
  • 55 Department of Physical Medicine and Rehabilitation, Harvard Medical School , Boston, Massachusetts.
  • 66 Spaulding Rehabilitation Hospital , Charlestown, Massachusetts.
  • 77 Massachusetts General Hospital , Boston, Massachusetts.
  • 88 Brigham and Women’s Hospital , Boston, Massachusetts.
  • 99 TBI Research Program, Spaulding Rehabilitation Hospital , Charlestown, Massachusetts.
  • 1010 Wellman Center for Photomedicine, Massachusetts General Hospital , Boston Massachusetts.
  • 1111 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.
  • 1212 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.
  • 1313 Boston University Center for Biomedical Imaging , Boston, Massachusetts.

Abstract

OBJECTIVE:

We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. Review of published studies: In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35?cm diameter, 500?mW, 22.2?mW/cm2) was applied for 9?min 45?sec (13?J/cm2) using 11 locations on the scalp: midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing studies: Ongoing, current studies involve TBI patients who have been treated with tLED using either 26?J/cm2 per LED location on the head or treated with intranasal only (iLED) using red (633?nm) and NIR (810?nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633?nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.

Photomed Laser Surg. 2016 Dec;34(12):587-598. doi: 10.1089/pho.2015.4051.

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

Thunshelle C1,2, Hamblin MR2,3,4.

Author information

  • 11 Harvard College , Cambridge, Massachusetts.
  • 22 Wellman Center for Photomedicine , Massachusetts General Hospital, Boston, Massachusetts.
  • 33 Department of Dermatology, Harvard Medical School , Boston, Massachusetts.
  • 44 Harvard-MIT Division of Health Sciences and Technology , Cambridge, Massachusetts.

Abstract

BACKGROUND:

Low-level laser therapy (LLLT) or photobiomodulation (PBM) is a possible treatment for brain injury, including traumatic brain injury (TBI).

METHODS:

We review the fundamental mechanisms at the cellular and molecular level and the effects on the brain are discussed. There are several contributing processes that have been proposed to lead to the beneficial effects of PBM in treating TBI such as stimulation of neurogenesis, a decrease in inflammation, and neuroprotection. Both animal and clinical trials for ischemic stroke are outlined. A number of articles have shown how transcranial LLLT (tLLLT) is effective at increasing memory, learning, and the overall neurological performance in rodent models with TBI.

RESULTS:

Our laboratory has conducted three different studies on the effects of tLLLT on mice with TBI. The first studied pulsed against continuous laser irradiation, finding that 10?Hz pulsed was the best. The second compared four different wavelengths, discovering only 660 and 810?nm to have any effectiveness, whereas 732 and 980?nm did not. The third looked at varying regimens of daily laser treatments (1, 3, and 14 days) and found that 14 laser applications was excessive. We also review several studies of the effects of tLLLT on neuroprogenitor cells, brain-derived neurotrophic factor and synaptogenesis, immediate early response knockout mice, and tLLLT in combination therapy with metabolic inhibitors.

CONCLUSIONS:

Finally, some clinical studies in TBI patients are covered.

KEYWORDS:

brain disorders; low-level laser therapy; photobiomodulation; stroke; traumatic brain injury

Lasers Med Sci. 2015 Jan;30(1):339-46. doi: 10.1007/s10103-014-1669-2. Epub 2014 Oct 3.

The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women.

Salgado AS1, Zângaro RA, Parreira RB, Kerppers II.
Author information
1Institute of Biomedical Engineering, Camilo Castelo Branco University, Unicastelo, S J dos Campos, São Paulo, 12247-004, Brazil, afonsosisalgado@yahoo.com.br.
.
Abstract
During aging processes, there is a range of functional changes, where we can highlight the disease related to the central nervous system, such as Alzheimer disease and others forms of dementia. This study investigated the effects of transcranial light emitting diode (LED) on cerebral blood flow in healthy elderly women analyzed by transcranial Doppler ultrasound (TCD) of the right and left middle cerebral artery and basilar artery. Twenty-five noninstitutionalized elderly women (mean age 72 years old), with a cognitive status >24, were assessed using transcranial Doppler ultrasound on two separate occasions: pre-irradiation and post-transcranial LED therapy (TCLT). Prior to this, they answered two questionnaires: the perceived stress scale and the general health questionnaire. TCLT (627 nm, 70 mW/cm(2), 10 J/cm(2)) was performed at four points of the frontal and parietal region for 30 s each, totaling 120 s two times per week for 4 weeks. Paired t-test results showed that there was a significant improvement after TCLT with increase in the systolic and diastolic velocity of the left middle cerebral artery (25 and 30%, respectively) and basilar artery (up to 17 and 25%), as well as a decrease in the pulsatility index and resistance index values of the three cerebral arteries analyzed (p<0.05). TCD parameters showed improvement in the blood flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women.
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.

Klin Khir. 2014 Mar;(3):37-40.

Comparative evaluation of effectiveness of the combined immunocorrection in patients suffering severe craniocerebral trauma.

[Article in Russian]
Marerrambe?li ISh, Mirzoeva VS.

Abstract

Comparative estimation of clinical efficacy of various immunocorrection schemes for the immune state correction was conducted in 106 patients in conditions ofsevere craniocerebral trauma (SCCT), combined application of immunofan and intravenous laser irradiation of blood (IVLIB). In 32 patients (I group) a standard intensive therapy (SITH) was conducted: in 21 (II group)–immunofan was applied additionally; in 25 (III group)–in addition to SITH IVLIB was conducted; in 28 (IV group)–immunofan solution was infused and sessions of IVLIB (3 – 4 sessions a day) on a background of SITH were conducted. The immunity indices were analyzed on the 1 – 2, 5 – 6-th and 9 -10-th days after trauma. Estimation of the combined therapy efficacy have shown, that in SCCT she renders a significant immunocorrecting effect on the 5 – 6-th days already, on the 9 – 10-th days the immune state parameters were really normalized, reduction of the complications rate by 26% and of lethality by 8.6% was noted.

PLoS One.  2013;8(1):e53454. doi: 10.1371/journal.pone.0053454. Epub 2013 Jan 7.

Transcranial low-level laser therapy improves neurological performance in traumatic brain injury in mice: effect of treatment repetition regimen.

Xuan W, Vatansever F, Huang L, Wu Q, Xuan Y, Dai T, Ando T, Xu T, Huang YY, Hamblin MR.

Source

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America ; Department of Dermatology, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Otolaryngology, Traditional Chinese Medical University of Guangxi, Nanning, China.

Abstract

Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm(2), 18 J/cm(2), spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21-27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1- and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1- and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed.

 

 

J Neurotrauma.  2012 Jan 20;29(2):401-7. doi: 10.1089/neu.2011.2062. Epub 2012 Jan 4.

Near infrared transcranial laser therapy applied at various modes to mice following traumatic brain injury significantly reduces long-term neurological deficits.

Oron A, Oron U, Streeter J, De Taboada L, Alexandrovich A, Trembovler V, Shohami E.

Source

Department of Zoology, Tel Aviv University, Faculty of Life Sciences, Tel Aviv 69978, Israel. oronu@post.tau.ac.il

Abstract

 

Near-infrared transcranial laser therapy (TLT) has been found to modulate various biological processes including traumatic brain injury (TBI). Following TBI in mice, in this study we assessed the possibility of various near-infrared TLT modes (pulsed versus continuous) in producing a beneficial effect on the long-term neurobehavioral outcome and brain lesions of these mice. TBI was induced by a weight-drop device, and neurobehavioral function was assessed from 1 h to 56 days post-trauma using the Neurological Severity Score (NSS). The extent of recovery is expressed as the difference in NSS (dNSS), the difference between the initial score and that at any other later time point. An 808-nm Ga-Al-As diode laser was employed transcranially 4, 6, or 8 h post-trauma to illuminate the entire cortex of the brain. Mice were divided into several groups of 6-8 mice: one control group that received a sham treatment and experimental groups that received either TLT continuous wave (CW) or pulsed wave (PW) mode transcranially. MRI was taken prior to sacrifice at 56 days post-injury. From 5-28 days post-TBI, the NSS of the laser-treated mice were significantly lower (p<0.05) than those of the non-laser-treated control mice. The percentage of surviving mice that demonstrated full recovery at 56 days post-CHI (NSS=0, as in intact mice) was the highest (63%) in the group that had received TLT in the PW mode at 100 Hz. In addition, magnetic resonance imaging (MRI) analysis demonstrated significantly smaller infarct lesion volumes in laser-treated mice compared to controls. Our data suggest that non-invasive TLT of mice post-TBI provides a significant long-term functional neurological benefit, and that the pulsed laser mode at 100 Hz is the preferred mode for such treatment.

J Neurotrauma.  2012 Jan 20;29(2):408-17. doi: 10.1089/neu.2010.1745. Epub 2011 Sep 21.

Low-level laser light therapy improves cognitive deficits and inhibits microglial activation after controlled cortical impact in mice.

Khuman J, Zhang J, Park J, Carroll JD, Donahue C, Whalen MJ.

Source

Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

 

Abstract

Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcomes after experimental traumatic brain injury (TBI), and coherent near-infrared light has been reported to improve cognitive function in patients with chronic TBI. However, the effects of LLLT on cognitive recovery in experimental TBI are unknown. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve post-injury Morris water maze (MWM) performance. Low-level laser light (800 nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80 min after CCI. Injured mice treated with 60 J/cm² (500 mW/cm²×2 min) either transcranially or via an open craniotomy had modestly improved latency to the hidden platform (p<0.05 for group), and probe trial performance (p<0.01) compared to non-treated controls. The beneficial effects of LLLT in open craniotomy mice were associated with reduced microgliosis at 48 h (21.8±2.3 versus 39.2±4.2 IbA-1+ cells/200×field, p<0.05). Little or no effect of LLLT on post-injury cognitive function was observed using the other doses, a 4-h administration time point and 7-day administration of 60 J/cm². No effect of LLLT (60 J/cm² open craniotomy) was observed on post-injury motor function (days 1-7), brain edema (24 h), nitrosative stress (24 h), or lesion volume (14 days). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI.

 

 

J Neurotrauma.  2011 Oct 31. [Epub ahead of print]

 

Near infrared Transcranial Laser Therapy applied at Various Modes to Mice Following Traumatic Brain Injury Significantly Reduces Long-Term Neurological Deficits.

Oron U.

Source

Ramat Aviv, Tel-Aviv, Israel, 69978; oronu@post.tau.ac.il.

Abstract

 

Near-infrared transcranial laser therapy (TLT) has been found to modulate various biological processes including traumatic brain injury (TBI). Following TBI in mice, in this study we assessed the possibility of various near-infrared TLT modes (pulsed vs. continuous) producing a beneficial effect on the long-term neurobehavioral outcome and brain lesions of these mice. TBI was induced by a weight-drop device, and neurobehavioral function was assessed from one hour and up to 56 days post-trauma using a neurological severity score (NSS). The extent of recovery is expressed as dNSS, the difference between the initial score, and that at any other, later, time point. An 808nm Ga-Al-As diode laser was employed transcranially 4, 6 or 8 hrs post-trauma to illuminate the entire cortex of the brain. Mice were divided into several groups of 6-8 mice: one control group that received a sham treatment and experimental groups that received either TLT continuous wave (CW) or pulsed wave (PW) mode transcranially. MRI was taken prior to sacrifice 56 days post-CHI. From 5 to 28 days post-TBI, the NSS of the laser-treated mice were significantly lower (p<0.05) than the non-laser-treated, control mice. The percentage of surviving mice that demonstrated full recovery 56 days post-CHI, namely NSS=0 (as in intact mice) was the highest (63%) in the group that had received TLT in the PW mode at 100 Hz. In addition, MRI analysis demonstrated significantly smaller infarct lesion volumes in laser treated mice as compared to control. Our data suggest that non-invasive TLT of mice post-TBI provides a significant long-term functional neurological benefit, and that the pulsed laser mode at 100 Hz is the preferred mode for such treatment. Key words: low-level laser therapy; mice; traumatic brain injury; pulsed laser; motor function, MRI.

 

 

PLos One. 2011;6(10):e26212. Epub 2011 Oct 18.

 

 

Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice.

Ando T, Xuan W, Xu T, Dai T, Sharma SK, Kharkwal GB, Huang YY, Wu Q, Whalen MJ, Sato S, Obara M, Hamblin MR.

Source

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

 

 

Abstract

BACKGROUND AND OBJECTIVE:

Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI.

STUDY DESIGN/MATERIALS AND METHODS:

TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2) for 12-minutes giving a fluence of 36-J/cm(2). Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test.

RESULTS:

The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests.

CONCLUSION:

The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.

 

 

J Neurotrauma.  2011 Aug 18. [Epub ahead of print]

Low-Level Laser Light Therapy Improves Cognitive Deficits and Inhibits Microglial Activation after Controlled Cortical Impact in Mice.

Khuman J, Zhang J, Park J, Carroll J, Whalen M.

Source

Massachusetts General Hospital , Neuroscience Center and Department of Pediatrics, 149 Thirteenth street, Charlestown, Massachusetts, United States, 02129; jugtakhuman@gmail.com.

Abstract

Low-level laser light therapy (LLLT) exerts beneficial effects on motor and histopathological outcome after experimental TBI (Oron et al., 2007), and coherent near infrared light has been reported to improve cognitive function in patients with chronic TBI (Naeser et al., 2010). However, effects of LLLT on cognitive recovery in experimental TBI are lacking. We hypothesized that LLLT administered after controlled cortical impact (CCI) would improve postinjury Morris water maze performance. Low-level laser light (800 nm) was applied directly to the contused parenchyma or transcranially in mice beginning 60-80 min after CCI. Injured mice treated with 60 J/cm2 (500 mW/cm2 x 2 min) either transcranially or via an open craniotomy had modestly improved latency to the hidden platform (p < 0.05 for group) and probe trial performance (p < 0.01) compared to non-treated controls. The beneficial effects of LLLT in open craniotomy mice were associated with reduced microgliosis at 48h (21.8 + 2.3 vs. 39.2 + 4.2 IbA-1+ cells/x200 field, p < 0.05). Little or no effect of LLLT on postinjury cognitive function was observed using other doses, a 4 h administration time point and 7 day administration of 60 J/cm2. No effect of LLLT (60 J/cm2 open craniotomy) was observed on postinjury motor function (d 1-7), brain edema (24 h), nitrosative stress (24 h), or lesion volume (14 d). Although further dose optimization and mechanism studies are needed, the data suggest that LLLT might be a therapeutic option to improve cognitive recovery and limit inflammation after TBI.

Photomed Laser Surg. 2010 Dec 23. [Epub ahead of print]

Improved Cognitive Function After Transcranial, Light-Emitting Diode Treatments in Chronic, Traumatic Brain Injury: Two Case Reports.

Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA.

1 VA Boston Healthcare System , Boston, Massachusetts.

Abstract

Objective: Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented.

Background: Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Methods: Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1? diameter, 61 diodes (9?×?633?nm, 52?×?870?nm); 12-15?mW per diode; total power: 500?mW; 22.2?mW/cm(2); 13.3?J/cm(2) at scalp (estimated 0.4?J/cm(2) to cortex)].

Results: Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment.

Conclusions: Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.

J Photochem Photobiol B.J Photochem Photobiol B. 2009 Dec 2;97(3):145-51. Epub 2009 Sep 11.

Effect of phototherapy with low intensity laser on local and systemic immodulation following focal brain damage in rat.

Moreira MS, Velasco IT, Ferreira LS, Ariga SK, Barbeiro DF, Meneguzzo DT, Abatepaulo F, Marques MM.LIM-51, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over therapeutic management for these patients. The objective of this study was to analyze the effect of phototherapy with low intensity lasers on local and systemic immunomodulation following cryogenic brain injury. Laser phototherapy was applied (or not-controls) immediately after cryogenic brain injury performed in 51 adult male Wistar rats. The animals were irradiated twice (3 h interval), with continuous diode laser (gallium-aluminum-arsenide (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP), 660 nm) in two points and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). The experimental groups were: Control (non-irradiated), RL3 (visible red laser/ 3 J/cm(2)), RL5 (visible red laser/5 J/cm(2)), IRL3 (infrared laser/3 J/cm(2)), IRL5 (infrared laser/5 J/cm(2)). The production of interleukin-1IL-1beta (IL-1beta), interleukin6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme immunoassay technique (ELISA) test in brain and blood samples. The IL-1beta concentration in brain of the control group was significantly reduced in 24 h (p<0.01). This reduction was also observed in the RL5 and IRL3 groups. The TNF-alpha and IL-6 concentrations increased significantly (p<0.01 and p<0.05, respectively) in the blood of all groups, except by the IRL3 group. The IL-6 levels in RL3 group were significantly smaller than in control group in both experimental times. IL-10 concentration was maintained stable in all groups in brain and blood. Under the conditions of this study, it is possible to conclude that the laser phototherapy can affect TNF-alpha, IL-1beta and IL-6 levels in the brain and in circulation in the first 24 h following cryogenic brain injury.

Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):3-11.

Many-level polysensory stimulation of brain functions by physical therapeutic agents.

[Article in Russian]

Tyshkevich TG, Ponomarenko GN.

A combination of physiotherapeutic methods for neurorehabilitative treatment has been developed and applied to the treatment of 576 patients with neurosurgical problems including the loss of brain functions as a sequel to nervous system lesions of traumatic, vascular, and other origin. Methodologically, this complex is adapted to the level and extent of the lesion and the character of regeneration of the nervous tissues. It implies many-level stimulation of neuroregeneration by syndromically and pathogenetically substantiated application of physical factors in the early post-injury and postoperative periods. The proposed approach allows the brain function to be completely restored by virtue of persistent compensatory changes in the nervous system. A combination of many-level magnetic, electrical, and laser stimulation is recommended to manage lesions in the speech, motor, and visual analyzers. Combined laser and differential electrostimulation may be prescribed to patients with nerve lesions, extremely high frequency therapy to those with epileptic syndrome, combined microwave therapy to cases with impairment of consciousness, and a variant of systemic UV irradiation with underwater shower-massaging for the treatment of vegetative and asthenic disturbances. Selected physiological aspects of the action of the above physical factors are specified. This physiotherapeutic system is protected by 20 RF patents of invention.

J Neurotrauma. 2007 Apr;24(4):651-6.

Low-level laser therapy applied transcranially to mice following traumatic brain injury significantly reduces long-term neurological deficits.

Oron A, Oron U, Streeter J, de Taboada L, Alexandrovich A, Trembovler V, Shohami E.

Department of Orthopedics, Assaf Harofeh Medical Center, Zerifin, Israel. amiroronmd@gmail.com

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.

Zhong Xi Yi Jie He Xue Bao. 2005 Mar;3(2):128-31.

Protective effect of low-level irradiation on acupuncture points combined with iontophoresis against focal cerebral ischemia-reperfusion injury in rats.

[Article in Chinese]

Dai JY, Ge LB, Zhou YL, Wang L.

Acupuncture Clinic, Institute of Qigong, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China. djysh2002@yahoo.com.cn

OBJECTIVE: To investigate the effects of low-level laser irradiation on acupuncture points combined with iontophoresis against brain damage after middle cerebral artery occlusion (MCAO) in rats.

METHODS: Sixty-nine SD rats were randomly divided into five groups, including normal group, sham operation group, model group, electro-acupuncture group and low-level laser irradiation on acupuncture points combined with iontophoresis group (LLLI group). The cerebral ischemia-reperfusion (I/R) model was established by thread embolism of middle cerebral artery. The rats in the LLLI group, as well as the electro-acupuncture group were given treatment as soon as the occlusion finished (0 hour) and 12, 24 hours after the occlusion. We observed the changes of neurological deficit scores and the body weight of the rats at different time. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ratos brain tissue were tested.

RESULTS: The neurological deficit score of the LLLI group was significantly lower than that of the model group. The body weight and the activity of SOD of the rats decreased slightly, and the content of MDA decreased significantly after the treatment.

CONCLUSION: The low-level laser irradiation on acupuncture points combined with iontophoresis can prevent focal cerebral ischemia-reperfusion injury. One of its mechanisms may be increasing the activity of SOD and decreasing the damage of the oxidation products to the body.

ACTA LASER BIOLOGY SINICA Vol. 8, No.2, 1999

Vascular Low Level Laser Irradiation Therapy in Treatment of Brain Injury

WANG Yu ZHU Jing, et al

(Department of Neurosurgery, Renji Hospital Affiliated to Shanghai Second Medical University, Shanghai Medical Centre for laser Research ,200001)

Abstract: To evaluate the effect and mechanism of Vascular Low Level Laser Irradiation Therapy on brain injury. In this study thirty-eight SpragueDawley rats received Feeney’s brain impact through a left lateral craniectomy under anesthesia. Control and treatment group are set up. According to the time exposed to laser and irradiating postinjury, the treatment group is divided in four subgroups by design. Semiconductor laser was used with a power of 5mW to irridate straightly Rat’s femur venous. The Y Water maze was used to assess cognitive performance. Superoxide dismutase(SOD) activity and the level of metabolic production of free radical MDA in Brain and erythrocyte were measured to determinate the level of free radical. We find Vascular Low Level Laser Irradiation Therapy can improve posttraumatic memory deficits. SOD activity is higher in treatment groups than the control group meanwhile the level of MDA is lower. These findings suggest that Vascular Low Level Laser Irradiation produced a significant reduction in free radical’s damage to the brain postinjury.

INFRARED LASER RADIATION IN THE TREATMENT OF BRAIN INJURY CONSEQUENCES

E.L. Macheret, A.O. Korkushko, T.N. Kalishchuk, M.N. Matyash

Medical Academy of Post-Diploma Education, Kiev, Ukraine

The examination of 198 patients aged 16-47 has revealed a high fre­quency of progressive pathologic states in a form of asthenia, vegeto-vascular dystonia, hypertensive, somato-vegetative, vestibular syndroms. Taking into account the changes in cortico-undercortical interrelations and expansion of pathologic process in hypothalamic area during the head trauma, we have developed effective treating methods by means of laseropuncture. Laser rays influence on acupuncture points (AP) leads to a convergence of the afferent messages upon the neurones of spinal cord, reticular formation, thalamus, hypothalamus and brain cor­tex. As a result of that a dynamic balance between the inhibition and excitation processes in the structures of central nervous system leading vegetative function and endocrine secretion recovers.  Use of infrared laser radiation is the most perspective. It docs not cause the direct photochemical reactions in biological tissues, but influences on physico-chemical structure of AP biomolecules. For laseropuncture we used an apparatus “BIOMED-01” with a wavelength of 0.89 nm. The work regime is impulsive-continuous with a modulation of frequency – from 0.1 to 1000 Hz. The middle power is up to 20 mW. The total time of the action for one sitting is till 20 min. The points selections was carried out on the grounds of the methods of acupuncture diagnosis, imagesking out the dominant clinical syndromes and including points of vascular, vegetotroimages, sedative orientation. Our clinical results, which were confirmed by paraclinical methods (EEG, dopplerography) and methods of acupuncture diagnosis have shown a high effectiveness of this therapy decreasing the drugs load and having no contradictions.

LASER-THERAPY AND ITS INFLUENCE ON HEMODYNAMICS WITH PATIENTS SUFFERED FROM GRAVE CRANIOCEREBRAL TRAUMA

Y.V. Kurako

Medical Academy, Dnepropetrovsk, Ukraine

Despite the maximal dosage of different medications taken for curing of grave craniocerebral trauma the resistance to the treatment carried out was observed. This fact stimulated the search of new methods and ways of therapy. One of the possible methods is a non-medicamental treatment based on blood irradiation with low-active helium-neon laser. The present paper presents some data concerning the laser-therapy influence in hemodynamics in the case of craniocerebral trauma. The total number of patients examined is 45. Laser-therapy was carried out through the subclavian vein (37 cases) or cubital vein (8 cases). For primary irradiation the preferable access was the central one. It was used in the acute period of craniocerebral trauma. The periferal access was used for irradiation in the posthospital period. The course of laser therapy for in-hospital patients consisted of 3-5 everyday procedures of 30 minutes each. To define the hemodynamic changes with the patients suffered from craniocerebral trauma both clinical observation and ultrasonic transcranial dopplerography were used. The last one gave the possibility to identify the type of blood flow speed disorders.