Photobiomodulation Therapy for a Novel Olfactory Dysfunction Ischemic Stroke Model

A. Background Ischemic stroke typically accompanies numerous disorders ranging from somatosensory dysfunction to cognitive impairments, inflicting its patients with various neurologic symptoms. Among pathologic outcomes, post-stroke olfactory dysfunction is frequently observed. Despite the well-known prevalence, therapy options for such compromised olfaction are limited, likely due to the complexity of the olfactory bulb architecture, which encompasses both the peripheral and central nervous systems. As photobiomodulation (PBM) emerged for treating stroke-associated symptoms, the effectiveness of PBM on the stroke-induced impairment of the olfactory function was explored. Purpose To address the efficacy of PBM therapy on the olfactory bulb damage caused by ischemic stroke using both behavioral and histologic and inflammatory markers in the newly developed stroke mouse models. Methods Novel mouse models with olfactory dysfunction were prepared using photothrombosis (PT) in the olfactory bulb on day 0. Moreover, post-PT PBM was performed daily from day 2 to day 7 by irradiating the olfactory bulb using an 808 nm laser with the fluence of 40 J/cm 2 (325 mW/cm 2 for 2 minutes per day). The buried food test (BFT) was used for scoring behavioral acuity in the food-deprived mice to assess the olfactory function before PT, after PT, and after PBM. Histopathological examinations and cytokine assays were performed on the mouse brains harvested on day 8. Results The results from BFT were specific to the individual, with positive correlations between the baseline latency time measured before PT and alterations at the ensuing stages for both the PT and PT+PBM groups. Also in both groups, the correlation analysis showed a significant positive relationship between the early and late latency time changes independent of PBM, implicating a common recovery mechanism. In particular, the PBM treatment largely accelerated the recovery of impaired olfaction after PT with the suppression of inflammatory cytokines while enhancing both the glial and vascular factors (e.g., GFAP, IBA-1, and CD31). Conclusions The PBM therapy during the acute phase of ischemia improves the compromised olfactory function by modulating the microenvuronment and tissue inflammation.