Transcranial near-infrared light promotes remyelination through AKT1/mTOR pathway to ameliorate postoperative neurocognitive disorder in aged mice

[Display omitted] •TNIRL is a non-invasive and effective treatment for cognitive impairment in PND mice.•Demyelination contributes ‘to the occurrence of PND and TNIRL promotes remyelination.•TNIRL may be a novel therapeutic approach for PND and other demyelination diseases. Postoperative neurocognitive disorder (PND) is a prevalent complication following surgery and anesthesia, characterized by progressive cognitive decline. The precise etiology of PND remains unknown, and effective targeted therapeutic strategies are lacking. Transcranial near-infrared light (tNIRL) has shown potential benefits for cognitive dysfunction diseases, but its effect on PND remains unclear. Our previous research indicated a close association between demyelination and PND. In other central nervous system (CNS) disorders, tNIRL has been demonstrated to facilitate remyelination in response to demyelination. In this study, we established the PND model in 18-month-old male C57BL/6 mice using isoflurane anesthesia combined with left common carotid artery exposure. Following surgery, PND-aged mice were subjected to daily 2.5-minute tNIRL treatment at 810 nm for three consecutive days. Subsequently, we observed that tNIRL significantly improved cognitive performance and reduced inflammatory cytokine levels in the hippocampus of PND mice. Furthermore, tNIRL increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP), promoting remyelination while enhancing synaptic function-associated proteins such as synaptophysin (SYP) and postsynaptic density protein 95 (PSD95). Further investigation revealed that tNIRL may activate the AKT1/mTOR pathway to facilitate remyelination in PND mice. These findings indicate that tNIRL is a novel non-invasive therapeutic approach for treating PND.