Abstract
Lipocalin-2 (LCN2) is a key mediator of various cellular processes. Recent studies have indicated that LCN2 also plays an important role in central nervous system (CNS) injuries and neurological diseases, such as spinal cord injury, stroke, experimental autoimmune encephalomyelitis, and neurodegenerative diseases. Here, we investigated the role of LCN2 in a rodent model of lipopolysaccharide (LPS)-induced neuroinflammation. At 24 hours after intraperitoneal injection of LPS, LCN2 expression was strongly induced in the brain; LCN2 was mainly expressed in endothelial cells, astrocytes, and microglia. Next, we used LCN2-deficient mice to further investigate the role of LCN2 in neuroinflammation. LCN2 deficiency attenuated LPS-induced glial activation in the brain. In a mechanistic study employing glia/neuron co-cultures, LCN2 deficiency reduced glial neurotoxicity. Our results indicate that LCN2 plays a central role in the neuroinflammatory responses following LPS administration, and that LCN2 might contribute to the uncontrolled neurotoxic glial activation under excessive and chronic inflammatory conditions.