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Transcranial low level laser (light) therapy for traumatic brain injury

Authors:

Abstract

We review the use of transcranial low-level laser (light) therapy (LLLT) as a possible treatment for traumatic-brain injury (TBI). The basic mechanisms of LLLT at the cellular and molecular level and its effects on the brain are outlined. Many interacting processes may contribute to the beneficial effects in TBI including neuroprotection, reduction of inflammation and stimulation of neurogenesis. Animal studies and clinical trials of transcranial-LLLT for ischemic stroke are summarized. Several laboratories have shown that LLLT is effective in increasing neurological performance and memory and learning in mouse models of TBI. There have been case report papers that show beneficial effects of transcranial-LLLT in a total of three patients with chronic TBI. Our laboratory has conducted three studies on LLLT and TBI in mice. One looked at pulsed-vs-continuous wave laser-irradiation and found 10 Hz to be superior. The second looked at four different laser-wavelengths (660, 730, 810, and 980 nm); only 660 and 810 nm were effective. The last looked at different treatment repetition regimens (1, 3 and 14-daily laser-treatments). (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
REVIEW ARTICLE
Transcranial low level laser (light) therapy
for traumatic brain injury
Ying-Ying Huang1;2;3, Asheesh Gupta1;2;4, Daniela Vecchio 1;2, Vida J. Bil de Arce1,
Shih-Fong Huang1;2;5, Weijun Xuan1;2;6, and Michael R. Hamblin*;1;2;7
1Wellman Center for Photomedicine, Massachusetts General Hospital, BAR414, 40 Blossom Street, Boston, MA 02114, USA
2Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA
3Aesthetic and Plastic Center of Guangxi Medical University, Nanning, China
4Defence Institute of Physiology and Allied Sciences, Timarpur, Delhi-110 054, India
5Taipei Veterans General Hospital, Beitou District, Taipei City, Taiwan 112
6Department of Otolaryngology, Traditional Chinese Medical University of Guangxi, Nanning, China
7Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
Received 26 April 2012, revised 12 June 2012, accepted 13 June 2012
Published online 17 July 2012
Key words: Low level laser therapy, photobiomodulation, NIR laser, traumatic brain injury, stroke, mouse models,
neurogenesis, clinical trials
1. Introduction
Traumatic brain injury (TBI) includes skull fractures,
intracranial hemorrhages, elevated intracranial pres-
sure, and cerebral contusion. Unlike stroke, which is
often associated with senior citizens, TBI affects a
predominantly young population. Severe and mod-
erate TBI, whether accidental or inflicted, is a major
health and socio-economic problem throughout the
world. In the United States alone, approximately
2 million injuries occur each year resulting in
56,000 deaths and 18,000 survivors suffering from
#2012 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Journal of
BIOPHOTONICS
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www.wileyonlinelibrary.com
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citable using Digital Object Identifier DOI)
We review the use of transcranial low-level laser (light)
therapy (LLLT) as a possible treatment for traumatic-
brain injury (TBI). The basic mechanisms of LLLT at the
cellular and molecular level and its effects on the brain
are outlined. Many interacting processes may contribute
to the beneficial effects in TBI including neuroprotec-
tion, reduction of inflammation and stimulation of neuro-
genesis. Animal studies and clinical trials of transcranial-
LLLT for ischemic stroke are summarized. Several la-
boratories have shown that LLLT is effective in increas-
ing neurological performance and memory and learning
in mouse models of TBI. There have been case report
papers that show beneficial effects of transcranial-LLLT
in a total of three patients with chronic TBI. Our labora-
tory has conducted three studies on LLLT and TBI in
mice. One looked at pulsed-vs-continuous wave laser-ir-
radiation and found 10 Hz to be superior. The second
looked at four different laser-wavelengths (660, 730, 810,
and 980 nm); only 660 and 810 nm were effective. The
last looked at different treatment repetition regimens (1,
3 and 14-daily laser-treatments).
Schematic of transcranial LLLT employed for stroke.
*Corresponding author: e-mail: hamblin@helix.mgh.harvard.edu, Phone: 617-726-6182, Fax: 617-726-8566
J. Biophotonics 1–11 (2012) / DOI 10.1002/jbio.201200077
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Traumatic brain injury (TBI) affects millions worldwide and is without effective treatment. One area that is attracting growing interest is the use of transcranial low-level laser therapy (LLLT) to treat TBI. The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may treat TBI by increasing respiration in the mitochondria, causing activation of transcription factors, reducing inflammatory mediators and oxidative stress, and inhibiting apoptosis. We tested LLLT in a mouse model of closed-head TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with continuous-wave 665, 730, 810, or 980 nm lasers (36 J/cm(2) delivered at 150 mW/cm(2)) 4-hour post-TBI and were followed up by neurological performance testing for 4 weeks. Mice with moderate-to-severe TBI treated with 665 and 810 nm laser (but not with 730 or 980 nm) had a significant improvement in Neurological Severity Score that increased over the course of the follow-up compared to sham-treated controls. Morphometry of brain sections showed a reduction in small deficits in 665 and 810 nm laser treated mouse brains at 28 days. The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT.
Article
This study aimed to quantify the cerebral blood flow (CBF) after bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to the forehead in a patient in a persistent vegetative state following severe head injury. Positive behavioral improvement has been observed following transcranial near-infrared light therapy in humans with chronic traumatic brain injury and acute stroke. Methods: Single-photon emission computed tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed following a series of LED treatments. IMP-SPECT showed unilateral, left anterior frontal lobe focal increase of 20%, compared to the pre-treatment value for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days from an array of 23×850 nm LEDs, 13 mW each, held 5 mm from the skin, 30 min per session, the power density 11.4 mW/cm(2); the energy density 20.5 J/cm(2) at the skin. The patient showed some improvement in his neurological condition by moving his left arm/hand to reach the tracheostomy tube, post-LED therapy. Transcranial LED might increase rCBF with some improvement of neurological condition in severely head-injured patients. Further study is warranted.