Transcranial photobiomodulation improves insulin therapy in diabetic microglial reactivity and the brain drainage system

The dysfunction of microglia in the development of diabetes is associated with various diabetic complications, while traditional insulin therapy is insufficient to rapidly restore the function of microglia. Therefore, the search for new alternative methods of treating diabetes-related dysfunction of microglia is urgently needed. Here, we evaluate the effects of transcranial photobiomodulation (tPBM) on microglial function in diabetic mice and investigate its mechanism. We find tPBM treatment effectively improves insulin therapy on microglial morphology and reactivity. We also show that tPBM stimulates brain drainage system through activation of meningeal lymphatics, which contributes to the removal of inflammatory factor, and increase of microglial purinergic receptor P2RY12. Besides, the energy expenditure and locomotor activity of diabetic mice are also improved by tPBM. Our results demonstrate that tPBM can be an efficient, non-invasive method for the treatment of microglial dysfunction caused by diabetes, and also has the potential to prevent diabetic physiological disorders. This work discovers that transcranial photobiomodulation enhances lymphatic clearance of inflammatory factors from the brain of diabetic mice, providing the reverse of microglial dysfunction and amelioration of physiological disorders.