Transcranial photobiomodulation improves insulin therapy in diabetic mice: modulation of microglia and the brain drainage system

Author:

Liu Shaojun1,Li Dongyu1,Yu Tingting1,Zhu Jingtan1,Semyachkina-Glushkovskaya Oxana2,Zhu Dan1

Affiliation:

1. Huazhong University of Science and Technology

2. Saratov State University

Abstract

Abstract Background: The chronic hyperglycemia of diabetes mellitus (DM) leads to the dysfunction of microglia, which is associated with the occurrence of diabetic cerebrovascular injuries (DCIs) and various complications, the main reasons of death in patients with DM. Although long term insulin therapy can effectively control blood glucose levels, it is not sufficient to rapidly restore the function of microglia. Therefore, the search for new alternative methods of treating diabetes-related dysfunction of microglia is urgently needed to improve the survival and quality of life of patients with DM. Methods: We evaluated the therapeutic effects of transcranial photobiomodulation (tPBM) at near infrared-Ⅱ wavelengths (1267 nm) with high tissue penetration depth on microglial function in diabetic mice. Afterwards, we investigated the mechanisms of tPBM in terms of changes in blood-brain barrier permeability and meningeal lymphatic vessels function. Results: The treatment of tPBM significantly improved insulin therapy via modulation of microglial morphology and reactivity to cerebrovascular injury. We also demonstrated that tPBM stimulated the brain drainage system through activation of the meningeal lymphatics contributing the removal of inflammatory factor, such as the interferon gamma (IFN-γ) from the brain parenchyma. These therapeutic effects of tPBM contribute the repair of microglial reactivity to the cerebrovascular injury via an increase in the expression of microglial chemokine receptor P2RY12. Conclusions: Our results demonstrate that tPBM can be an efficient innovative method for the treatment of microglial dysfunction caused by diabetes to prevent diabetic brain disorders and has the potential to be quickly introduced in clinical practice since tPBM is widely used for the therapy of brain diseases.

Publisher

Research Square Platform LLC

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