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

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.

Conflict of interest statement

Author Disclosure Statement No competing financial interests exist.

Figures

FIG. 1.

Molecular mechanisms of transcranial LLLT. Light passes through the scalp and skull, where it is then absorbed by cytochrome c oxidase in the mitochondrial respiratory chain of the cortical neurons in the brain. Cell signaling and messenger molecules are upregulated as a result of stimulated mitochondrial activity, including ROS, NO, and ATP. These signaling molecules activate transcription factors, including NF-κB and AP-1, which enter the nucleus and cause transcription of a range of new gene products. AP-1, activator protein 1; ATP, adenosine triphosphate; BDNF, brain-derived neurotrophic factor; LLLT, low-level laser therapy; NF-κB, nuclear factor kappa B; NGF, nerve growth factor; NO, nitric oxide; ROS, reactive oxygen species.

FIG. 2.

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

FIG. 3.

Effect of different wavelengths in tLLLT in closed head TBI in mice. (A) Sham-treated control versus 665 nm laser. (B) Sham-treated control versus 730 nm laser. (C) Sham-treated control versus 810 nm laser. (D) Sham-treated control versus 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 analysis of variance). NSS, neurological severity score; SD, standard deviation; TBI, traumatic brain injury; tLLLT, transcranial LLLT.

FIG. 4.

Effects of pulsing in transcranial LLLT for CCI-TBI in mice. (A) Time course of 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 ± SEM **p < 0.01 and ***p < 0.001 versus the other conditions. (B) Mean areas under the NSS time curves in the two-dimensional coordinate system over the 28-day study for the four groups of mice. Results are mean ± SD (n = 10). AUC, area under the curve; CCI, controlled cortical impact; CW, continuous wave; n.s., not significant; PW, pulsed wave.