Figure 10.

Graphical summary of the proposed role of LCN2 in disease-associated neurocognitive decline. During acute inflammatory disease, LCN2 is robustly induced by several CNS cells, including endothelium and glia, and protects the brain from invading pathogens. Acute exposure of LCN2 in the brain is not harmful to neurons. Conversely, during prolonged inflammatory disease, LCN2 is selectively produced and secreted by brain endothelium, particularly in pial vessels proximal to the hippocampus. This continued production and secretion of LCN2 during chronic disease results in a distinct microglial polarization phenotype, immune cell invasion, and prolonged neuronal stress, ultimately leading to neuronal dysfunction and impaired spatial memory.