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.
Highlights
Incidences of traumatic brain injury (TBI) in both developed and developing countries are in rise
We observed greater improvements in group 1 compared to group 7 that became especially noticeable as time progressed up to 28 days post-TBI
The integrated neurological severity score (NSS) value of the group of real-TBI 14 active laser Tx was significantly worse than the group of real-TBI 3 active laser Tx (P,0.001) and worse that the group of real-TBI 1 active laser Tx (P,0.01)
Summary
Incidences of traumatic brain injury (TBI) in both developed and developing countries are in rise. The lack of any approved therapy for TBI, combined with the failure of many clinical trials of pharmaceutical drugs that have been investigated for TBI, has motivated researchers to a widen their range in search of novel therapeutic interventions [3,4]. These intervention avenues can be grouped into therapies that could potentially affect oxidative stress [5]; inflammation [6]; excitotoxicity [7]; metabolic dysfunction [8]; dysregulated neurochemical pathways [9]; impaired circulation [10]; brain hypoxia [11]; could increase neuroprotection [12] or stimulate neurogenesis [2] and could induce brain repair by stem cells [13]. Some physical intervention methods, such as brain hypothermia, have shown encouraging results [14]
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