Enhanced neuroprotective effects of combined photobiomodulation and hydrogen inhalation in a mouse model of hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury (HIBI) is characterized by complex pathological processes that contribute to acute neuronal damage. Photobiomodulation (PBM) and hydrogen inhalation have each demonstrated neuroprotective effects in ischemic and hypoxic models; however, the effects of their combined application in acute HIBI have not been directly evaluated. In this study, HIBI was induced in mice, followed by treatment with PBM alone, hydrogen inhalation alone, or their combination. Behavioral performance, physiological parameters, and molecular markers of neuronal survival, glial activation, neuroinflammation, apoptosis, and hypoxia signaling were evaluated at 24 h after injury. While PBM or hydrogen alone partially attenuated HIBI-induced alterations, combined treatment more effectively preserved locomotor activity, stabilized physiological parameters, and reduced neuronal loss. These effects were accompanied by decreased glial activation and inflammatory signaling, suppression of apoptotic pathways, and improved regulation of hypoxia-related signaling. Collectively, these findings demonstrate that combined PBM and hydrogen inhalation confers enhanced neuroprotection compared with monotherapies by modulating multiple pathological mechanisms in acute HIBI.