Transcranial Low-Level Laser Therapy Improves Neurological Performance in Traumatic Brain Injury in Mice: Effect of Treatment Repetition Regimen

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/cm2, 18 J/cm2, 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.

Significant Improvements in Cognitive Performance Post-Transcranial, Red/Near-Infrared Light-Emitting Diode Treatments in Chronic, Mild Traumatic Brain Injury: Open-Protocol Study

“…36 Multiple animal studies using mice, show significantly better recovery of motor and cognitive function after NIR transcranial low-level laser therapy when treated in the acute post-injury phase. [37][38][39][40] Most of this work has suggested improved energy kinetics and decreased inflammation as possible mechanisms for acute neuroprotection. Energetics may also have a role in the chronic phase of injury.…”

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

“…Nevertheless, we were able to successfully demonstrate a significant enhancement of the neurogenic potential of RA (released from LR-NP) when combined with laser light in vivo. Recent data using low-level laser therapy revealed that near-infrared light (NIR) is capable of improving neurological performance in both patients and animal models of traumatic brain injury [41][42][43]. Interestingly, 18 J/cm 2 of NIR, the same fluence we used in our study, was able to increase the number of new neurons in the SVZ of mice with traumatic brain injury [43].…”

The influence of low-level laser irradiation on spinal cord injuries following ischemia- reperfusion in rats

“…The therapeutic effects of LLLT have been reported, being associated with production of anti-apoptotic, pro-proliferative, antioxidant, and angiogenic factors [31][32][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.…”