Abstract
Background: Photobiomodulation (PBM) utilizing 1064 nm near-infrared light, renowned for its deep tissue penetration capabilities, has demonstrated significant therapeutic potential in addressing brain disorders; however, its specific effects and underlying mechanisms in traumatic brain injury (TBI) remain poorly understood. Methods: This study investigated the therapeutic efficacy of 1064 nm light-emitting diodes (LED) treatment on emotional and cognitive impairments in a murine TBI model, and elucidating potential molecular mechanisms. C57BL/6 mice were systematically allocated into Sham, TBI, and TBI + PBM intervention groups, with the latter receiving daily 1064 nm light treatment (25 mW/cm2, 12 min/day) for 14 consecutive days post-TBI induction. Comprehensive behavioral assessments were conducted to evaluate emotional and cognitive functions. Advanced molecular analyses encompassing transcriptome sequencing, immunofluorescence, quantitative RT-PCR, and Western blot were employed to examine brain tissue damage, neurogenesis, synaptic remodeling, and inflammatory responses. Results: The 1064 nm LED treatment demonstrated remarkable therapeutic effects, significantly ameliorating anxiety, depression-like behaviors, and spatial cognitive deficits in TBI mice. Behavioral improvements were evidenced by enhanced rotarod performance, increased exploratory behavior in open field and elevated plus maze tests, and improved Y-maze alternation rates. At the molecular level, PBM intervention exhibited multifaceted neuroprotective effects, including inhibition of neuronal apoptosis, reduction of brain injury, promotion of neurogenesis and synaptic remodeling, and upregulation of neurotrophic factors. Furthermore, the treatment enhanced blood-brain barrier integrity through upregulation of tight junction proteins and modulated neuroinflammation by shifting microglia and astrocytes toward anti-inflammatory phenotypes. Conclusions: These findings collectively demonstrate that 1064 nm wavelength PBM treatment effectively promotes functional recovery and mitigates both emotional and cognitive impairments in TBI mice, providing novel mechanistic insights and a promising wavelength option for PBM-based therapeutic strategies in TBI management.