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

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).

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figures

Figure 1

Molecular mechanisms of transcranial LLLT. Light passes through the scalp and the skull, whereupon it is absorbed by cytochrome c oxidase in the mitochondrial respiratory chain of the cortical neurons. Cell signaling and messenger molecules are upregulated as a result of stimulated mitochondrial activity, including reactive oxygen species (ROS), nitric oxide (NO), and adenosine triphosphate (ATP). These signaling molecules activate transcription factors including NF-κB and AP-1 that enter the nucleus and cause transcription of a range of new gene products.

Figure 2

Functional mechanisms of transcranial LLLT. The gene transcription described in Figure 1 can lead to decreases in neuronal apoptosis and excitotoxicity and lessening of inflammation and edema that will help reduce progressive brain damage. Increases in angiogenesis, expression of neurotrophins leading to activation of neural progenitor cells and incrar4sed synaptogenesis may all contribute to the brain repairing itself from damage sustained in the trauma.

Figure 3

Schematic of transcranial LLLT employed for stroke. 808 nm laser spot sequentially applied twenty times to cover the whole head.

Figure 4

Transcranial LLLT for chronic TBI. Showing right and left forehead placement areas for transcranial LED treatments performed by the patient at home, using a single, circular-shaped cluster head. The usual treatment time is 10 minutes per area (13.3 J/cm2). Reprinted with permission from Naeser et al. [55].

Figure 5

Effect of different laser wavelengths in transcranial LLLT in closed head TBI in mice. Time course of NSS scores of sham and laser-treated mice. (A) Sham-treated control vs 665 nm laser, (B) Sham-treated control vs. 730 nm laser, (C) Sham-treated control vs. 810 nm laser, (D) Sham-treated control vs. 980 nm laser, Points are means of 8–12 mice and bars are SD. *p < 0.05; **p < 0.01; ***p < 0.001 (one-way ANOVA). Reprinted with permission from Wu et al. [58].

Figure 6

Effect of pulsing in transcranial LLLT for CCI-TBI in mice. (A) Time course of neurological severity score (NSS) of mice with TBI receiving either control (no laser-treatment), or 810 nm laser (36 J/cm2 delivered at 50 mW/cm2 with a spot size of 0.78 cm2) in either CW, PW 10 Hz or PW 100 Hz modes. Results are expressed as mean ± S.E.M (n = 10). ***P < 0.001 vs. the other conditions. Mean areas under the NSS-time curves in the two-dimensional coordinate system over the 28-day study for the 4 groups of mice. Results are means ± SD (n = 10). Reprinted with permission from Ando et al. [60].