Low-level laser therapy enhances neuroprotection and functional recovery after neonatal hypoxic–ischemic injury via potential activation of Nrf2/HO-1 and Akt pathways

Neonatal hypoxic–ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental disability. Low-level laser therapy (LLLT), or photobiomodulation, has shown neuroprotective potential, but its long-term effects and region-specific responses remain poorly defined. Neonatal rats subjected to hypoxic–ischemic brain damage (HIBD) received transcranial 810-nm LLLT (24 mW/cm², 10 min/session, twice daily for three days). Histological, immunofluorescence, and Western blot analyses assessed neuronal integrity, glial activation, and signaling pathway changes. Sensorimotor function was evaluated by grip traction and open-field tests, and spatial learning and memory were assessed using the Morris water maze (MWM) at long-term follow-up. LLLT reduced neuronal loss and glial reactivity and was associated with increased Nrf2/HO-1 and Akt signaling at early time points. Behaviorally, LLLT improved motor and cognitive performance, with benefits persisting up to 20 weeks post-injury. Early LLLT is associated with sustained functional recovery after neonatal hypoxic–ischemic injury. These effects may involve early modulation of antioxidant and pro-survival signaling pathways, although the mechanisms underlying long-term outcomes require further investigation.