## 4 Light Therapy for Mitigation/Treatment of Stroke  
### Light Therapy for Stroke Based on Photobiomodulation  
Photobiomodulation means a use of light in selected wavelengths for purposes of healing tissues, enhancing a recovery speed, alleviating pain, or restoring function [110; 111; 112; 113]. Among several types of photobiomodulation, a method of irradiating light to the brain for performing functions of treatments, recovery and symptom mitigation is called transcranial photobiomodulation [114; 115; 116; 117; 118], and light with spectral bands of red or infrared is generally employed in this process due to its relatively high penetration efficiency. Several research groups have studied transcranial photobiomodulation for brain diseases in three categories: stroke/ischem, degenerative diseases (such as Alzheimer's disease), and psychiatric diseases (for instance, bipolar disorder). This section explores the latest progress and important points regarding the studies focused on transcranial photobiomodulation to stroke and its consequent brain injuries. Several research groups conducted preclinical studies on small and middle-sized animals to identify effects of therapeutic optical stimulation on treatment of stroke and symptoms related to it. [PERSON] et al. explored a possibility of recovering neurological deficits caused by a stroke using low-level laser therapy with a peak wavelength of 808 nm in a rat stroke model, which was established using a middle cerebral artery to create a permanent occlusion (MCAO) [119]. The quantitative estimation of neurological deficits from six behavioral tests confirmed that the therapeutic photostimulation on both sides (i.e., a stroke-induced side and on an opposite side improved neurological deficits after stroke). An immunohistochemical analysis of neurons using Bromodeoxyuridine and Tubulin isotype III also confirmed a decrease in neurological damages using therapeutic photostimulation with an 808 nm laser at 7.5 mW/cm\({}^{2}\)[120]. Preclinical tests using a rabbit stroke model, where stroke was caused by artificially injecting blood clot particles, also indicated that pulsed near-infrared laser irradiations aid healing of brain damages [121]. In this study, a significant impact was observed on a treatment of pulsed photostimulation under two different conditions (1000 Hz with a duty cycle of 30% and 100 Hz with a duty cycle of 20%, with a power density = 7.5 mW/cm\({}^{2}\)) after 6 h of stroke. However, no therapeutic effect of continuous laser irradiation could be observed when compared statistically with control results, as illustrated in Figure 6. [PERSON] et al. employed a light emitting diode (LED), with 610 nm as a peak wavelength, in a preclinical study of photostimulation-based stroke therapies [122]. Furthermore, light irradiation using the LED-integrated medical device prototype was applied to a photothrombotic mouse stroke model, and a possibility of using the LED-integrated medical device to treat stroke and mitigate resultant symptoms was confirmed through a comparison of a volume of ischemic brain damages with a control model that was untreated. Moreover, a functional recovery from treatments through the LED-integrated medical device was verified using immunofluorescence assays (Bromodeoxyuridine and an astrocyte marker) [123]. [PERSON] et al. examined preclinical tests to apply infrared (830 nm) LEDs to treatments based on photobiomodulation after an ischemic stroke [124]. Specifically, these researchers applied the therapeutic photostimulation to rats that were subjected to stroke by a transient MCAO, and employed functional MRI (_f_MRI) to explore functional recoveries of the brain area where ischemic stroke was induced. Although the study could not identify a recovery of stroke-induced lesions and functional reduction due to stroke by LED-based optical neurostimulation, it confirmed that fMRI is a sufficient modality to validate an efficiency of therapeutic photostimulation, both structurally and functionally.