Photobiomodulation Promotes Early Recovery of Olfactory Function and Modulates Neuroprotective Gene Expression in a Mouse Model of Ischemic Stroke

Abstract

Ischemic stroke often leads to neurological deficits, including olfactory dysfunction, which can significantly diminish quality of life. Photobiomodulation (PBM) has emerged as a promising therapeutic strategy for enhancing post-stroke recovery, although the molecular mechanisms, particularly regarding gene expression change, are not yet fully understood. This study investigates the long-term effects of photothrombosis (PT) on olfactory function and the olfactory bulb (OB) microenvironment, with a focus on PBM's efficacy during both early and late phases. In a mouse OB PT stroke model, PBM therapy (808-nm laser, 40 J/cm2 fluence, 325 mW/cm2, 2 min daily) was applied from day 2 to day 7 post-PT. Olfactory function was monitored from pre-stroke through day 28 using the buried food test (BFT), and MRI scans were performed on days 7 and 28 to assess tissue damage. RNA sequencing (RNA-seq) and reverse transcription quantitative PCR (RT-qPCR) were conducted on day 7 to evaluate gene expression changes, with additional RT-qPCR analyses performed on day 28. PBM significantly accelerated olfactory function recovery by day 14, with full recovery maintained through day 28. Despite functional recovery, MRI results indicated persistent infarction at 28 days. RNA-seq identified upregulation of neuroprotective genes, including Gpr39 and Or4m1, following PBM treatment, suggesting enhanced gene expression related to acute-phase recovery. However, the impact of PBM on gene expression and functional recovery appeared to wane in the later stages of recovery. These findings underscore PBM's potential to enhance early-stage recovery in ischemic stroke, though its benefits may be more limited in the chronic phase.