Background Traumatic brain injury (TBI), as a neurological disorder characterized by high disability and mortality rates, demands urgent innovation in therapeutic approaches. Although photobiomodulation (PBM) demonstrates potential as a novel non-invasive physical therapy, current research lacks systematic investigation into its mechanisms of action and efficacy parameters specifically for moderate traumatic brain injury.

Objective To investigate the neuroprotective effects and potential mechanisms of 1064 nm PBM in moderate TBI models.

Methods Thirty six 8-week-old male C57BL/6 mice were randomized into sham group, TBI group, and PBM group. The TBI group and the PBM group were established using controlled cortical impact injury to model moderate brain injury, while the sham group underwent identical craniotomy procedures without cortical impact induction. The PBM group received daily 1064 nm irradiation (25 mW/cm², 12 min/day) for 14 consecutive days. Behavioral assessments employing rotarod fatigue testing and Y-maze paradigms were implemented to quantify locomotor coordination and spatial working memory, while histopathological evaluation utilizing immunofluorescence staining on cryopreserved cerebral sections enabled quantitative analysis of glial fibrillary acidic protein (GFAP) astrogliosis and microtubule-associated protein 2 (MAP2) neuronal integrity, complemented by molecular profiling through quantitative real-time PCR (RT-qPCR) that systematically measured transcriptional alterations in brain-derived neurotrophic factor (BDNF) and astrocyte-mediated pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) within peri-contusional parenchyma.

Results ​In behavioral tests​, the fatigue rotarod test showed that compared to the TBI group​​, the PBM group exhibited a longer average fall latency, a significantly increased travel distance, and a higher falling speed (P < 0.05). In the Y-maze test, compared to the TBI group, the PBM group demonstrated increased time spent exploring the novel arm and more entries into the novel arm (P < 0.05).​Histologically, the TBI group exhibited significantly lower mean fluorescence intensity of MAP2 and significantly higher GFAP fluorescence intensity in the injured brain region compared to both the sham and PBM groups (all P < 0.05). Molecular analysis by RT-qPCR showed that the PBM group had significantly increased BDNF mRNA expression levels in the injured area relative to the TBI group (P < 0.05), while cellular studies revealed that PBM treatment significantly reduced the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in activated astrocytes (P < 0.05).

Conclusion 1064 nm PBM may improve motor and cognitive functions after moderate TBI by promoting the repair of neuronal damage, inhibiting the activation of astrocytes, as well as decreasing their levels of pro-inflammatory factors.