Fig. 4
From: The restorative role of annexin A1 at the blood–brain barrier
Schematic representation of possible mechanisms linking metabolic disorders, BBB dysfunction and neurodegeneration. Metabolic imbalance associated with obesity and DM leads to chronic systemic, low-grade inflammation and the down-regulation of circulating ANXA1. Interaction of circulating soluble factors with brain endothelial cells induces tight junction disruption and BBB leakage, permitting leukocyte migration and glial activation, which in turn can impair neuronal function through production of pro-inflammatory mediators and reactive oxygen species (AGEs advanced glycation end-products; ROS reactive oxygen species)