Photobiomodulation preconditioning prevents cognitive impairment in a neonatal rat model of hypoxia-ischemia

Neonatal hypoxia-ischemia (HI) injury caused by oxygen deprivation is the most common cause of mortality and severe neurologic deficits in neonates. The present work evaluated the preventative effect of photobiomodulation (PBM) preconditioning, and its underlying mechanism of action on brain damage in an HI model in neonatal rats. According to the optimal time response of ATP levels in brain samples removed from normal rats, a PBM preconditioning (PBM-P) regimen (808 nm CW laser, 1 cm² spot, 100 mW/cm², 12 J/cm²) was delivered to the scalp 6 hours before HI. PBM-P significantly attenuated cognitive impairment, volume shrinkage in the brain, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation found that PBM-P could restore HI-induced mitochondrial dynamics and inhibit mitochondrial fragmentation, followed by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Our work suggests that PBM-P can attenuate HI-induced brain injury by maintaining mitochondrial dynamics and inhibiting the mitochondrial apoptotic pathway.