Diabetes Mellitus Impairs Blood‐Brain Barrier Integrality and Microglial Reactivity

ABSTRACT Diabetes mellitus (DM), a chronic metabolic disorder that adversely affects the blood–brain barrier (BBB) and microglial function in the central nervous system (CNS), contributing to neuronal damage and neurodegenerative diseases. However, the underlying molecular mechanisms linking diabetes to BBB dysfunction and microglial dysregulation remain poorly understood. Here, we assessed the impacts of diabetes on BBB and microglial reactivity and investigated its mechanisms. We found diabetes severely disrupted the BBB integrity and microglial response to vascular injury. We also revealed a potential relationship between BBB disruption and impaired microglial function, whereby increasing BBB permeability led to a downregulation of microglial P2RY12 expression, thereby impairing microglial protection against cerebrovascular injury. Understanding these mechanisms may contribute to the developing of therapeutic strategies for diabetes‐related neurological complications.