Abstract
Photobiomodulation (PBM) therapy is a promising therapeutic approach for several pathologies, including stroke. The biological effects of PBM for the treatment of cerebral ischemia have previously been explored as a neuroprotective strategy using different light sources, wavelengths, and incident light powers. However, the capability of PBM as a novel alternative therapy to stimulate the recovery of the injured neuronal tissue after ischemic stroke has been poorly explored. The aim of this study was to investigate the low-level light irradiation therapy by using Light Emitting Diodes (LEDs) as potential therapeutic strategy for stroke. The LED photobiomodulation (continuous wave, 830 nm, 0.2–0.6 J/cm2) was firstly evaluated at different energy densities in C17.2 immortalized mouse neural progenitor cell lines, in order to observe if this treatment had any effect on cells, in terms of proliferation and viability. Then, the PBM-LED effect (continuous wave, 830 nm, 0.28 J/cm2 at brain cortex) on long-term recovery (12 weeks) was analyzed in ischemic animal model by means lesion reduction, behavioral deficits, and functional magnetic resonance imaging (fMRI). Analysis of cellular proliferation after PBM was significantly increased (1 mW) in all different exposure times used; however, this effect could not be replicated in vivo experimental conditions, as PBM did not show an infarct reduction or functional recovery. Despite the promising therapeutic effect described for PBM, further preclinical studies are necessary to optimize the therapeutic window of this novel therapy, in terms of the mechanism associated to neurorecovery and to reduce the risk of failure in futures clinical trials.
Highlights
Photobiomodulation therapy has been investigated in the past few years as an alternative treatment for stroke and traumatic brain injury (TBI) in order to promote a neuroprotective effect and tissue regeneration [1,2,3,4,5]
We have studied the long-term recovery effect of Light Emitting Diodes (LEDs)-PBM in an animal model of transient ischemic stroke by means of reduction of ischemic lesion size, and we have tested for the first time functional recovery determined by functional magnetic resonance imaging (fMRI) in combination with functional behavioral tests
Other therapeutic studies with very different treatments, as stem cells, but where fMRI was used to evaluate the functional recovery after ischemic stroke have evidenced that the regaining of BOLD signal was produced between the 7th and the 10th week after the administration [33]
Summary
Photobiomodulation therapy has been investigated in the past few years as an alternative treatment for stroke and traumatic brain injury (TBI) in order to promote a neuroprotective effect and tissue regeneration [1,2,3,4,5]. Some studies have demonstrated that 808–660 nm Low Level Laser Therapy (LLLT) applied after ischemia on experimental animals improved neurological rating scores without increasing body temperature, by direct illumination of the skin on shaved animals [7,8,9,10]. Despite experimental evidences and human safety, a clinical trial designed to analyze the beneficial effect nearinfrared laser therapy in stroke has showed negative results, in part because many of the parameters used (therapeutic timewindow, laser intensity) were not sufficiently optimized for use in animal preclinical studies [14]
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